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1.
J Clin Pathol ; 73(10): 656-664, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32591352

RESUMO

AIMS: Programmed death-1/programmed death ligand 1 (PD-1/PD-L1) inhibitor therapy is accompanied by companion or complementary PD-L1 testing in some tumour types. We investigated utilisation of the Dako PD-L1 IHC 28-8 and 22C3 pharmDx assays and the Ventana PD-L1 (SP142) assay and evaluated concordance between the 28-8 and 22C3 assays in a real-world cohort of patients tested at a single US national reference laboratory. METHODS: NeoGenomics Laboratories performed PD-L1 testing on tumour samples between October 2015 and March 2018. PD-L1 test results were matched with patient characteristics using unique identifiers. Concordance between the 28-8 and 22C3 assays was evaluated in matched tumour samples. Data were evaluated across multiple tumour types and in subgroups of patients with lung cancer, melanoma, squamous cell carcinoma of the head and neck, and urothelial carcinoma. RESULTS: 62 180 individual PD-L1 tests were conducted on samples from 55 652 patients. PD-L1 test volume increased ~10-fold over the period evaluated. Test failure rates were typically low, and test turnaround time (TAT) ranged between 2 and 4 days. Concordance between the 28-8 and 22C3 assays was strong in the overall population and across tumour type subgroups (Kendall's tau correlations of 0.94 and 0.92-0.98, respectively). CONCLUSIONS: Test failure rates for PD-L1 tests were low and TAT remained reasonable despite marked increases in test volume. Concordance was high between the 28-8 and 22C3 assays across a range of tumour types and biopsy locations. These findings add to the literature showing high concordance between the 28-8 and 22C3 assays.


Assuntos
Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Imuno-Histoquímica , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/normas , Imuno-Histoquímica/estatística & dados numéricos , Neoplasias/metabolismo , Reprodutibilidade dos Testes
2.
In Vivo ; 34(2): 639-647, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32111764

RESUMO

BACKGROUND/AIM: To evaluate the association between programmed cell death ligand 1 (PD-L1) expression on both tumor cells (TC) and inflammatory cells (IC), tumor infiltrating lymphocytes (TILs), CD3+ and CD8+ lymphocytes and other clinicopathological parameters in primary infiltrative breast cancer (IBC) of young women, a population shown to have a worse prognosis. MATERIALS AND METHODS: A retrospective study was performed collecting data from patients younger than 40 years old. Forty-five young women with IBC were included. Whole tissue sections were used to evaluate all parameters. RESULTS: Twenty percent (20%) of cases showed PD-L1 expression by tumor cells (PDL1TC) and 44.4% showed PD-L1 expression by immune cells (PDL1IC). Furthermore, 28.88% revealed high stromal TILs. PDL1TC and PDL1IC expression were significantly associated with tumor diameter and expression of estrogen (ER) and progesterone (PR) receptors and Ki67. PDL1TC expression was also associated with grade. High TILs were associated with tumor diameter, ER and Ki67 expression. PDL1TC, PDL1IC expression and TILs were associated with the density of CD3+ and CD8+ lymphocytes. CONCLUSION: Our results are similar to those of other age groups, as reported in the literature.


Assuntos
Antígeno B7-H1/biossíntese , Neoplasias da Mama/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Adulto , Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/patologia , Complexo CD3/biossíntese , Feminino , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/estatística & dados numéricos , Antígeno Ki-67/biossíntese , Prognóstico , Receptores Estrogênicos/biossíntese , Receptores de Progesterona/biossíntese , Estudos Retrospectivos
3.
Medicina (Kaunas) ; 56(2)2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32059385

RESUMO

Background and objectives: B-lymphoma Mo-MLV insertion region 1 (Bmi-1) is a stem cell factor that is overexpressed in various human cancer tissues. It has been implicated in cancer cell proliferation, cell invasion, distant metastasis, and chemosensitivity, and is associated with patient survival. Several reports have also identified Bmi-1 protein overexpression in endometrial carcinoma; however, the relationship between Bmi-1 expression and its significance as a clinicopathological parameter is still insufficiently understood. Accordingly, the present study aimed to clarify whether immunohistochemical staining for Bmi-1 in human endometrial carcinoma and normal endometrial tissues can be used as a prognostic and cell proliferation marker. Materials and Methods: Bmi-1 expression was assessed in endometrioid carcinoma (grade 1-3) and normal endometrial tissues (in the proliferative and secretory phases) by immunohistochemistry; protein expression was evaluated using the nuclear labeling index (%) in the hot spot. Furthermore, we examined other independent prognostic and proliferation markers, including the protein levels of Ki-67, p53, and cyclin A utilizing semi-serial sections of endometrial carcinoma tissues. Results: The expression of the Bmi-1 protein was significantly higher in all grades of endometrial carcinoma than in the secretory phase of normal tissues. Moreover, Bmi-1 levels tended to be higher in G2 and G3 tissues than in G1 tissue, without reaching significance. Bmi-1 expression showed no notable differences among International Federation of Gynecology and Obstetrics (FIGO) stages in endometrial carcinoma. Furthermore, we observed a significant positive relationship between Bmi-1 and Ki-67, cyclin A, or p53 by Spearman's rank correlation test, implying that high Bmi-1 expression can be an independent prognostic marker in endometrial carcinoma. Conclusions: Our study suggests that Bmi-1 levels in endometrial carcinoma tissues may be useful as a reliable proliferation and prognostic biomarker. Recently, the promise of anti-Bmi-1 strategies for the treatment of endometrial carcinoma has been detected. Our results provide fundamental data regarding this anti-Bmi-1 strategy.


Assuntos
Neoplasias do Endométrio/diagnóstico , Imuno-Histoquímica/normas , Complexo Repressor Polycomb 1/análise , Valor Preditivo dos Testes , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Biópsia/métodos , Ciclina A/análise , Detecção Precoce de Câncer/métodos , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/estatística & dados numéricos , Japão , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Complexo Repressor Polycomb 1/sangue , Proteína Supressora de Tumor p53/análise
4.
Medicine (Baltimore) ; 98(37): e17104, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517842

RESUMO

Esophageal cancer is a common human malignant tumor with high mortality. Glandular epithelial markers, such as CAM5.2, can be expressed in esophageal squamous cell carcinoma (ESCC), but the clinical significance of these cells in ESCC remains elusive.Immunohistochemical analysis of CAM5.2 was performed on 604 ESCC specimens using tissue microarray. Our study design and study population used retrospective cohorts based on the hospital information system and pathological information management system which included medical information, date of admission, procedures undergone, registration, examinations, and medication.In total, positive staining of CAM5.2 was 145 of 604 (24%). Statistical analysis showed that the expression of CAM5.2 had no relationship with sex, age, tumor differentiation, tumor size, tumor-node-metastasis (TNM) classification, and lymph node metastasis, but it was significantly associated with poor prognosis of overall survival (P = .0041) and disease-free survival (P = .0048) in ESCC patients.Herein, we report for the first time that the high expression of the CAM 5.2 is an independent predictor of poor prognosis in patients with ESCC.


Assuntos
Biomarcadores/análise , Neoplasias Esofágicas/classificação , Carcinoma de Células Escamosas do Esôfago/complicações , Queratinas/análise , Queratinas/genética , Adulto , Idoso , Biópsia/métodos , Biópsia/estatística & dados numéricos , China , Estudos de Coortes , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transcriptoma
5.
Cancer Cytopathol ; 127(10): 632-642, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509355

RESUMO

BACKGROUND: Many patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HPV-HNSCC) initially present with cervical lymph node metastases. Although p16 immunohistochemistry (IHC) is the most commonly used surrogate marker for HPV, however criteria in cytologic material are not well established. The objective of this study was to better characterize p16 IHC in cell blocks of metastatic HPV-HNSCC, and to evaluate the performance of HPV RNA in situ hybridization (RNA ISH). METHODS: p16 IHC was performed on cell blocks from 97 metastatic HPV-HNSCC fine-needle aspiration specimens with HPV status confirmed by DNA or RNA ISH or polymerase chain reaction (PCR). Tumor cellularity (<100 cells, 100-500 cells, and >500 cells) and quality (presence of cell clusters, necrosis) were recorded. p16 staining intensity and extent (1%-9%, 10%-69%, and ≥70%) were scored. In addition, RNA ISH was performed on 38 PCR-positive cases. RESULTS: p16 IHC was positive in 90 of 97 cases (93%), demonstrating variable patterns. p16 staining was found to be moderate to strong in 69 cases, with 37 cases (38%) demonstrating positivity in ≥70% of tumor cells. Weak staining occurred in 21 cases (22%) and 7 cases (7%) were negative. Of the 60 cases with weak and/or absent expression or staining in <70% of cells, 30 cases (50%) had <100 tumor cells, 12 (20%) lacked cell clusters, and 19 cases (32%) had extensive necrosis. RNA ISH was positive in 37 of 38 cases (97%) that were HPV positive by PCR. CONCLUSIONS: p16 is heterogeneous in cell blocks of metastatic HPV-HNSCC, suggesting that any p16 positivity should prompt confirmatory HPV studies. RNA ISH appears to demonstrate high sensitivity, and laboratories even may consider using RNA ISH as a first-line HPV test in cytologic specimens.


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Neoplasias de Cabeça e Pescoço/diagnóstico , Hibridização In Situ/métodos , Infecções por Papillomavirus/diagnóstico , RNA Viral/isolamento & purificação , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Biópsia por Agulha Fina , Estudos de Coortes , Inibidor p16 de Quinase Dependente de Ciclina/análise , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , DNA Viral/genética , DNA Viral/isolamento & purificação , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/virologia , Testes de DNA para Papilomavírus Humano/estatística & dados numéricos , Humanos , Imuno-Histoquímica/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , RNA Viral/genética , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia
6.
Indian J Gastroenterol ; 38(4): 317-324, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31401730

RESUMO

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) protein overexpression and/or HER2 gene amplification are/is linked to a dismal outcome of gastric carcinoma (GCa). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are key methods to identify patients for HER2 targeted therapy. Drawbacks of both the methods warrant novel tests. Hence, we evaluated the value of quantitative real-time polymerase chain reaction (qPCR) as an alternative test method, relative to IHC to detect HER2 status of GCa and to find relationship between these  results with demographic/clinicopathological data. METHOD: Twenty GCa patients with known IHC HER2 scores were evaluated. qPCR was performed for the HER2 gene and amyloid precursor protein (reference gene) in formalin-fixed paraffin-embedded GCa tissue. Cycle threshold values (Ct) were analyzed using the Pfaffl method to detect HER2 gene amplification. RESULTS: HER2 positivity rates by IHC and qPCR were 20% and 35%, respectively. The sensitivity and specificity of qPCR were 67% and 76%, respectively, relative to IHC. qPCR results were reproducible. The diagnostic consistency between IHC and qPCR (κ = 0.146) was slightly agreeable (0.01 < k < 0.20), with a 65% concordance. Based on McNemar's test, there was no significant difference between the results of the two tests. IHC HER2 protein expression had relationship with the tumor (TNM) stage and Lauren histological type (p < 0.05). Positive HER2 gene expression by qPCR showed relationship with depth of invasion, lymph node involvement, and degree of differentiation (p < 0.05). CONCLUSION: Cost-effective qPCR could serve as an alternative test method for detection of HER2 status of GCa. Both HER2 overexpression by IHC and gene amplification by qPCR are associated with adverse clinicopathological features.


Assuntos
Carcinoma/genética , Imuno-Histoquímica/estatística & dados numéricos , Reação em Cadeia da Polimerase em Tempo Real/estatística & dados numéricos , Receptor ErbB-2/análise , Neoplasias Gástricas/genética , Adulto , Biomarcadores Tumorais/análise , Estudos Transversais , Feminino , Amplificação de Genes , Humanos , Imuno-Histoquímica/métodos , Masculino , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Sri Lanka
7.
Am J Dermatopathol ; 41(7): 488-491, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31233404

RESUMO

BACKGROUND: Dermatopathologists routinely use Ki67 immunostaining to assess atypical melanocytic lesions with a dermal component to determine whether an ambiguous tumor is melanoma. However, there is no universal standard of use for Ki67 in melanocytic neoplasms. We sought to observe the real-world use of Ki67 in the diagnosis of melanocytic lesions and establish a best practice recommendation. METHODS: We searched dermatopathology reports from 2 academic practices for melanocytic lesions in which Ki67 staining was used for diagnosis. The proliferation rate was compared between cases diagnosed as benign (not requiring re-excision), moderate to severely dysplastic or atypical Spitz nevi (requiring re-excision), and malignant melanoma. The use of other melanocytic markers and consensus review was also recorded and compared between institutions. RESULTS: Pathology reports for 106 cases were reviewed. A high Ki67 proliferation rate (n = 18) favored a diagnosis of melanoma or nevi requiring re-excision (15/18, 83.3%) versus a benign nevus (3/18, 16.67%). A high Ki67 rate was 71.4%-90.9% sensitive and 40%-56% specific for the diagnosis of nevus requiring re-excision or melanoma. Institutional practices differed in regard to reporting of Ki67 staining, the use of multiple markers in the workup of atypical melanocytic lesions (HMB45, Melan-A, Ki67 being most common), and consensus review. CONCLUSIONS: A negative or low Ki67 proliferation rate correlates well with rendering of a benign diagnosis. However, a low proliferation rate does not preclude the diagnosis of melanoma. Ki67 staining is most commonly used as an ancillary test to support a diagnosis after other factors have been considered, such as histopathologic morphology and results of additional concurrently used stains.


Assuntos
Antígeno Ki-67/metabolismo , Melanoma/diagnóstico , Nevo de Células Epitelioides e Fusiformes/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Imuno-Histoquímica/estatística & dados numéricos , Masculino , Melanoma/metabolismo , Melanoma/cirurgia , Pessoa de Meia-Idade , Índice Mitótico , Nevo de Células Epitelioides e Fusiformes/metabolismo , Nevo de Células Epitelioides e Fusiformes/cirurgia , Reoperação , Sensibilidade e Especificidade , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/cirurgia , Adulto Jovem
8.
J Transl Med ; 17(1): 198, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185999

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is classified into germinal center-like (GCB) and non-germinal center-like (non-GCB) cell-of-origin groups, entities driven by different oncogenic pathways with different clinical outcomes. DLBCL classification by immunohistochemistry (IHC)-based decision tree algorithms is a simpler reported technique than gene expression profiling (GEP). There is a significant discrepancy between IHC-decision tree algorithms when they are compared to GEP. METHODS: To address these inconsistencies, we applied the machine learning approach considering the same combinations of antibodies as in IHC-decision tree algorithms. Immunohistochemistry data from a public DLBCL database was used to perform comparisons among IHC-decision tree algorithms, and the machine learning structures based on Bayesian, Bayesian simple, Naïve Bayesian, artificial neural networks, and support vector machine to show the best diagnostic model. We implemented the linear discriminant analysis over the complete database, detecting a higher influence of BCL6 antibody for GCB classification and MUM1 for non-GCB classification. RESULTS: The classifier with the highest metrics was the four antibody-based Perfecto-Villela (PV) algorithm with 0.94 accuracy, 0.93 specificity, and 0.95 sensitivity, with a perfect agreement with GEP (κ = 0.88, P < 0.001). After training, a sample of 49 Mexican-mestizo DLBCL patient data was classified by COO for the first time in a testing trial. CONCLUSIONS: Harnessing all the available immunohistochemical data without reliance on the order of examination or cut-off value, we conclude that our PV machine learning algorithm outperforms Hans and other IHC-decision tree algorithms currently in use and represents an affordable and time-saving alternative for DLBCL cell-of-origin identification.


Assuntos
Algoritmos , Perfilação da Expressão Gênica , Centro Germinativo/patologia , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/patologia , Aprendizado de Máquina , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Teorema de Bayes , Árvores de Decisões , Análise Discriminante , Feminino , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/estatística & dados numéricos , Humanos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/estatística & dados numéricos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Masculino , Pessoa de Meia-Idade
9.
Ann Diagn Pathol ; 41: 124-128, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31238192

RESUMO

INTRODUCTION: Flat urothelial lesions fall into one of four diagnostic categories including urothelial carcinoma in-situ (CIS). There is morphologic overlap between the categories leading to immunohistochemistry (IHC) utilization in difficult cases. The purpose of this study was to examine the frequency, variation and utility of IHC use in bladder biopsy specimens over a 17 year period. METHODS: A search of "CD44", "p53", and "CK20" keywords was conducted from the pathology files (1/1/2003 to 12/31/2017) on bladder biopsy specimens at our institution. Atypical (AUS), dysplastic (UD) and CIS rates were calculated. RESULTS: A total of 4597 cases were identified. IHC was performed on 345 specimens (7.5%, 345/4597). For cases without IHC (H&E only), the AUS rate was 4.8% (206/4252), UD rate was 9.4% (399/4252), and the CIS rate was 8.4% (359/4252). For IHC cases, the AUS rate was 5.2% (18/345), the UD rate was 8.1% (28/345), and the CIS rate was 11.3% (39/345). There was no statistical difference between the H&E only or IHC rates (p > 0.05). The absolute number IHC orders per year increased until 2011 (60 cases) but drastically declined over the last five years (5 total cases in 2017). The CIS rates have remained relatively constant. CONCLUSION: We found the AUS, UD and CIS rates were similar regardless of IHC use. Our institution was an early adopter of IHC and it quickly fell out of favor. We agree with the ISUP in that IHC has limited clinical utility for flat urothelial lesions and morphology remains the gold standard.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma in Situ/diagnóstico , Carcinoma de Células de Transição/diagnóstico , Imuno-Histoquímica/estatística & dados numéricos , Neoplasias da Bexiga Urinária/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Sci Rep ; 9(1): 6992, 2019 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-31061447

RESUMO

Prostate cancer (PCa) is a major cause of cancer death among men. The histopathological examination of post-surgical prostate specimens and manual annotation of PCa not only allow for detailed assessment of disease characteristics and extent, but also supply the ground truth for developing of computer-aided diagnosis (CAD) systems for PCa detection before definitive treatment. As manual cancer annotation is tedious and subjective, there have been a number of publications describing methods for automating the procedure via the analysis of digitized whole-slide images (WSIs). However, these studies have focused only on the analysis of WSIs stained with hematoxylin and eosin (H&E), even though there is additional information that could be obtained from immunohistochemical (IHC) staining. In this work, we propose a framework for automating the annotation of PCa that is based on automated colorimetric analysis of both H&E and IHC WSIs stained with a triple-antibody cocktail against high-molecular weight cytokeratin (HMWCK), p63, and α-methylacyl CoA racemase (AMACR). The analysis outputs were then used to train a regression model to estimate the distribution of cancerous epithelium within slides. The approach yielded an AUC of 0.951, sensitivity of 87.1%, and specificity of 90.7% as compared to slide-level annotations, and generalized well to cancers of all grades.


Assuntos
Adenocarcinoma/diagnóstico , Colorimetria/estatística & dados numéricos , Imuno-Histoquímica/estatística & dados numéricos , Neoplasias da Próstata/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Área Sob a Curva , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biópsia por Agulha , Estudos de Coortes , Colorimetria/métodos , Amarelo de Eosina-(YS) , Hematoxilina , Humanos , Interpretação de Imagem Assistida por Computador , Imuno-Histoquímica/métodos , Queratinas/genética , Queratinas/metabolismo , Masculino , Estadiamento de Neoplasias , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Racemases e Epimerases/genética , Racemases e Epimerases/metabolismo , Sensibilidade e Especificidade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
11.
J Pediatr Gastroenterol Nutr ; 68(5): 689-694, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30540707

RESUMO

OBJECTIVE: Recent studies show increased serum and esophageal IgG4 in patients with eosinophilic esophagitis (EoE), suggesting a possible IgG4-involved process. The role of IgG4 in pediatric EoE has not been extensively investigated. Our aim was to analyze IgG4 in esophageal tissue in children in parallel to that in adults with EoE. METHODS: In a retrospective institutional review board-approved study, we performed immunohistochemical staining of IgG4 in esophageal biopsy specimens from 39 subjects: children with EoE (n = 16), adults with EoE (n = 15), children with reflux esophagitis (n = 4), and pediatric controls (n = 4). We assessed the relationships between IgG4 staining and clinical, endoscopic, and histopathologic characteristics. RESULTS: Patients with EoE were significantly more likely to stain positively for IgG4 than children with reflux esophagitis or controls (P = 0.015). Fifteen of 31 (48%) EoE cases stained positively for IgG4. None of the reflux esophagitis or control cases stained positively. IgG4 staining had 48% sensitivity and 100% specificity for EoE. There was a trend toward IgG4 staining being associated with foreign body/food impaction (P = 0.153). There was a strong association between distal IgG4 staining and basal zone hyperplasia (P = 0.003). CONCLUSIONS: Our study suggests IgG4 is not a consistent finding of EoE at disease diagnosis. Although IgG4 staining was specific for EoE, it had a poor sensitivity with positive staining in only 48% of EoE patients. Further studies are warranted to fully elucidate the role of IgG4 in EoE.


Assuntos
Esofagite Eosinofílica/diagnóstico , Esofagite Péptica/diagnóstico , Esôfago/química , Imunoglobulina G/análise , Imuno-Histoquímica/estatística & dados numéricos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Esofagoscopia/estatística & dados numéricos , Esôfago/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
12.
J Cell Biochem ; 120(6): 10186-10194, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30582216

RESUMO

Nasopharyngeal carcinoma (NPC) has a unique and complex etiology, which is not completely understood. The aim of this study is to investigate the expression patterns of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB), and mammalian target of rapamycin (mTOR) proteins in patients with NPC and their relationship with NPC progression and prognosis. Between January 2008 and March 2010, PI3K, PKB, and mTOR protein expressions were detected using immunohistochemistry among 119 patients with NPC and 30 healthy people. A 5-year follow-up was conducted for all patients. Correlations of PI3K, PKB, and mTOR proteins with the clinicopathological features and prognosis of NPC were evaluated using Spearman's rank correlation coefficient and Kaplan-Meier curve. Cox's regression analysis was performed to analyze the risk factors for the prognosis of NPC. First, PI3K, PKB, and mTOR were highly expressed in patients with NPC. The expressions of PI3K, PKB, and mTOR proteins were associated with T stage, N stage, clinical stage, relapse, and distant metastasis. Meanwhile, PI3K is positively correlated with PKB and PKB is positively correlated with mTOR in NPC. Higher PI3K, PKB, and mTOR protein expressions were related to a shorter survival time and a lower survival rate in NPC. Cox regression analysis revealed that age, T stage, N stage, PI3K, PKB, and mTOR were independent risk factors for NPC patient survival. Altogether, our data suggest that overexpression of PI3K, PKB, and mTOR proteins is an important indicator of poor survival in NPC. In addition, inhibition of PI3K-PKB-mTOR signaling may also contribute to the development of new therapeutic strategies for NPC.


Assuntos
Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Fosfatidilinositol 3-Quinase/biossíntese , Proteínas Proto-Oncogênicas c-akt/biossíntese , Serina-Treonina Quinases TOR/biossíntese , Adulto , Idoso , Progressão da Doença , Ativação Enzimática , Feminino , Humanos , Imuno-Histoquímica/estatística & dados numéricos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Adulto Jovem
13.
Appl Immunohistochem Mol Morphol ; 27(9): 694-698, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30499817

RESUMO

BACKGROUND: Utilization rates of immunohistochemistry (IHC) for the diagnosis of Helicobacter pylori infection may vary by laboratory and/or pathologists. IHC for H. pylori is not performed routinely in our practice. Instead, it is used in selected cases at the pathologists' discretion (and according to their specific criteria). The purpose of this study was to determine if IHC utilization rates correlated with rates of detecting H. pylori infection. MATERIALS AND METHODS: We searched our records and investigated all gastric biopsies for 1 calendar year. H. pylori diagnostic rate and IHC utilization rate was calculated for each pathologist. RESULTS: Overall, the rate of diagnosis was 12.1% and the IHC utilization rate was 45.2%. Individual pathologists had H. pylori diagnostic rates ranging from 3.6% to 34.1% (median: 11.1%) and IHC utilization ranging from 17.1% to 95.2% (median: 42.2%). The rate of detection of H. pylori infection among pathologists showed no significant correlation with rates of IHC utilization (Pearson coefficient=0.121). CONCLUSIONS: Increasing use of IHC is not independently associated with the diagnostic rate of infection. Ultimately, if we assume that the case mix was similar for each pathologist, it suggests that more liberal criteria to order IHC does not result in more infections diagnosed.


Assuntos
Mucosa Gástrica/patologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/fisiologia , Imuno-Histoquímica/estatística & dados numéricos , Utilização de Procedimentos e Técnicas/estatística & dados numéricos , Adulto , Biópsia , Testes Diagnósticos de Rotina , Feminino , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Coloração e Rotulagem , Estados Unidos/epidemiologia
14.
Popul Health Manag ; 22(1): 83-89, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29927702

RESUMO

Colorectal cancer (CRC) causes more than 50,000 deaths each year in the United States but early detection through screening yields survival gains; those diagnosed with early stage disease have a 5-year survival greater than 90%, compared to 12% for those diagnosed with late stage disease. Using data from a large integrated health system, this study evaluates the cost-effectiveness of fecal immunochemical testing (FIT), a common CRC screening tool. A probabilistic decision-analytic model was used to examine the costs and outcomes of positive test results from a 1-FIT regimen compared with a 2-FIT regimen. The authors compared 5 diagnostic cutoffs of hemoglobin concentration for each test (for a total of 10 screening options). The principal outcome from the analysis was the cost per additional advanced neoplasia (AN) detected. The authors also estimated the number of cancers detected and life-years gained from detecting AN. The following costs were included: program management of the screening program, patient identification, FIT kits and their processing, and diagnostic colonoscopy following a positive FIT. Per-person costs ranged from $33 (1-FIT at 150ng/ml) to $92 (2-FIT at 50ng/ml) across screening options. Depending on willingness to pay, the 1-FIT 50 ng/ml and the 2-FIT 50 ng/ml are the dominant strategies with cost-effectiveness of $11,198 and $28,389, respectively, for an additional AN detected. The estimates of cancers avoided per 1000 screens ranged from 1.46 to 4.86, depending on the strategy and the assumptions of AN to cancer progression.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Imuno-Histoquímica , Sangue Oculto , Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/estatística & dados numéricos , Fezes/química , Feminino , Humanos , Imuno-Histoquímica/economia , Imuno-Histoquímica/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade
15.
Comput Methods Programs Biomed ; 165: 37-51, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30337080

RESUMO

BACKGROUND AND OBJECTIVE: This paper presents an improved scheme able to perform accurate segmentation and classification of cancer nuclei in immunohistochemical (IHC) breast tissue images in order to provide quantitative evaluation of estrogen or progesterone (ER/PR) receptor status that will assist pathologists in cancer diagnostic process. METHODS: The proposed segmentation method is based on adaptive local thresholding and an enhanced morphological procedure, which are applied to extract all stained nuclei regions and to split overlapping nuclei. In fact, a new segmentation approach is presented here for cell nuclei detection from the IHC image using a modified Laplacian filter and an improved watershed algorithm. Stromal cells are then removed from the segmented image using an adaptive criterion in order to get fast tumor nuclei recognition. Finally, unsupervised classification of cancer nuclei is obtained by the combination of four common color separation techniques for a subsequent Allred cancer scoring. RESULTS: Experimental results on various IHC tissue images of different cancer affected patients, demonstrate the effectiveness of the proposed scheme when compared to the manual scoring of pathological experts. A statistical analysis is performed on the whole image database between immuno-score of manual and automatic method, and compared with the scores that have reached using other state-of-art segmentation and classification strategies. According to the performance evaluation, we recorded more than 98% for both accuracy of detected nuclei and image cancer scoring over the truths provided by experienced pathologists which shows the best correlation with the expert's score (Pearson's correlation coefficient = 0.993, p-value < 0.005) and the lowest computational total time of 72.3 s/image (±1.9) compared to recent studied methods. CONCLUSIONS: The proposed scheme can be easily applied for any histopathological diagnostic process that needs stained nuclear quantification and cancer grading. Moreover, the reduced processing time and manual interactions of our procedure can facilitate its implementation in a real-time device to construct a fully online evaluation system of IHC tissue images.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/metabolismo , Interpretação de Imagem Assistida por Computador/métodos , Imuno-Histoquímica/métodos , Algoritmos , Neoplasias da Mama/classificação , Carcinoma Ductal de Mama/classificação , Núcleo Celular/classificação , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/estatística & dados numéricos , Imuno-Histoquímica/estatística & dados numéricos , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Coloração e Rotulagem , Aprendizado de Máquina não Supervisionado
16.
PLoS One ; 13(1): e0188983, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29304138

RESUMO

Ki67 is a commonly used marker of cancer cell proliferation, and has significant prognostic value in breast cancer. In spite of its clinical importance, assessment of Ki67 remains a challenge, as current manual scoring methods have high inter- and intra-user variability. A major reason for this variability is selection bias, in that different observers will score different regions of the same tumor. Here, we developed an automated Ki67 scoring method that eliminates selection bias, by using whole-slide analysis to identify and score the tumor regions with the highest proliferative rates. The Ki67 indices calculated using this method were highly concordant with manual scoring by a pathologist (Pearson's r = 0.909) and between users (Pearson's r = 0.984). We assessed the clinical validity of this method by scoring Ki67 from 328 whole-slide sections of resected early-stage, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. All patients had Oncotype DX testing performed (Genomic Health) and available Recurrence Scores. High Ki67 indices correlated significantly with several clinico-pathological correlates, including higher tumor grade (1 versus 3, P<0.001), higher mitotic score (1 versus 3, P<0.001), and lower Allred scores for estrogen and progesterone receptors (P = 0.002, 0.008). High Ki67 indices were also significantly correlated with higher Oncotype DX risk-of-recurrence group (low versus high, P<0.001). Ki67 index was the major contributor to a machine learning model which, when trained solely on clinico-pathological data and Ki67 scores, identified Oncotype DX high- and low-risk patients with 97% accuracy, 98% sensitivity and 80% specificity. Automated scoring of Ki67 can thus successfully address issues of consistency, reproducibility and accuracy, in a manner that integrates readily into the workflow of a pathology laboratory. Furthermore, automated Ki67 scores contribute significantly to models that predict risk of recurrence in breast cancer.


Assuntos
Neoplasias da Mama/química , Processamento de Imagem Assistida por Computador/métodos , Antígeno Ki-67/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Automação Laboratorial/métodos , Automação Laboratorial/estatística & dados numéricos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Estudos de Coortes , Feminino , Humanos , Processamento de Imagem Assistida por Computador/estatística & dados numéricos , Imuno-Histoquímica/métodos , Imuno-Histoquímica/estatística & dados numéricos , Aprendizado de Máquina , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/química , Recidiva Local de Neoplasia/patologia , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Viés de Seleção
17.
Rev. guatemalteca cir ; 23(1): [3-8], ene-dic,2017. Tab
Artigo em Espanhol | LILACS | ID: biblio-884875

RESUMO

Introducción: El cáncer de mama es la primera causa de mortalidad en el mundo y en Guatemala ocupa el segundo lugar en frecuencia. Desde 1991 su clasifcación ha evolucionado a fn de mejorar el pronóstco y su tratamiento basado en la descripción del tpo y grado histológico. El objetvo de este estudio es conocer la aplicación actual de la inmunohistoquímica en cancer de mama. Metodología: Estudio observacional descriptvo retrospectvo, sobre cáncer de mama clasifcado por inmunohistoquímica en 281 pacientes en el Insttuto Guatemalteco de Seguridad Social (IGSS) de enero 2012 a enero del 2017. Resultados: El subtpo Luminal A se presentó en el 31% de los pacientes y su tratamiento fue principalmente hormonal; seguido por el Triple Negatvo en el 26% tratado mayoritariamente con quimioterapia. El HER2 Positvo en el 21%, el subtpo B-like 13% y en menor frecuencia el Luminal B en el 9% de los casos. El subtpo triple negatvo presento mayor recurrencia y mortalidad con mayor elevación del P53 (40%, OR 2.4) y Ki67 (37%, OR 1.4). La edad en la mayoría de pacientes incluidas fueron superiores a los 40 años y los estadios II y III se presentaron con mayor frecuencia. Conclusiones: El estudio de la inmunohistoquímica realizado en los tejidos obtenidos permitó mostrar que el subtpo luminal A fue el más frecuente, recibiendo en la mayoría de los casos tratamiento hormonal. El más agresivo en recurrencia, metástasis, mortalidad y con valor elevado del Gen p53 y Ki67, fue el Triple Negatvo, tratado con quimioterapia.


Background: Breast cancer is the leading cause of death in the world, and in Guatemala it is the second most common cause of death. Since 1991, its classifcaton has evolved in order to improve prognosis and treatment based on the descripton of type and histological grade. The purpose of this study is to learn the current applicaton of immunohistochemistry of breast cancer. Methods: This retrospectve descriptve observatonal study of breast cancer classifed by immunohistochemistry was performed on 281 patents at the Guatemalan Social Security Insttute (IGSS) between January 2012 and January 2017. Results: The subtype Luminal A was present in 31% of the patents and treatment was mainly hormonal; followed by Triple Negatve in 26% of patents treated mainly with chemotherapy. HER2 positve in 21% of patents, subtype B-like in 13% and lower frequency Luminal B in 9% of the patents. The triple negatve subtype presented higher recurrence and mortality with P53 elevaton (40%, OR 2.4) and Ki67 (37%, OR 1.4). Average age in the study was 40 years old and stages II and III were more frequent. Conclusions: The study of immunohistochemistry performed on tssue obtained, demonstrated that Luminal A subtype is the most frequent, in which the majority of patents received hormonal treatment. The most aggressive in recurrence, metastasis, mortality and with high values of gene p53 and Ki67, was the Triple Negatve, which were treated with chemotherapy.


Assuntos
Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Imuno-Histoquímica/estatística & dados numéricos , Menopausa , Estudo Observacional
18.
J Cutan Pathol ; 44(11): 938-943, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28796379

RESUMO

Human papillomaviruses have been implicated in many cutaneous diseases. Practicing dermatopathologists often consider using immunohistochemistry and in situ hybridization to help clarify the histologic diagnosis, particularly in cases with borderline or nondiagnostic features. We reviewed the current evidence behind the use of these two techniques in dermatopathology. We identified only two studies utilizing the currently available immunohistochemical antibodies. We found more evidence regarding the use of in situ hybridization; however, the majority of this evidence focuses on diagnosing condylomas and other lesions of the genital skin. We also assessed current utilization patterns of attendees of the American Society of Dermatopathology annual meeting (Chicago, 2016) which revealed a wide spectrum of current utilization ranging from no use to regular use more than once per month. Two-thirds of respondents utilized these tests primarily when requested by the submitting clinician and one-third of the respondents utilize these tests reflexively in specific clinical scenarios.


Assuntos
Dermatologia/métodos , Imuno-Histoquímica/estatística & dados numéricos , Hibridização In Situ/estatística & dados numéricos , Infecções por Papillomavirus/diagnóstico , Patologia/métodos , DNA Viral/análise , Humanos , Dermatopatias/diagnóstico , Dermatopatias/virologia
19.
Cardiovasc Pathol ; 30: 23-26, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28759816

RESUMO

Phospholamban (PLN) p.Arg14del cardiomyopathy is associated with an increased risk of malignant ventricular arrhythmias and severe heart failure and a poor prognosis from late adolescence. It can be diagnosed in whole heart specimens, but rarely in right ventricular biopsy specimens, by PLN immunohistochemistry showing PLN-containing aggregates concentrated in cardiomyocytes in dense perinuclear aggresomes. The purpose of this study was to determine whether PLN immunohistochemistry can be used to diagnose PLN p.Arg14del cardiomyopathy using apical left ventricular myocardial specimens harvested during left ventricular assist device (LVAD) implantation. At that stage, a genetic diagnosis, which may guide treatment and referral of family members for further investigation, is frequently not established yet. Included were myocardial specimens from 30 diverse genetic cardiomyopathy cases with known variants (9 carriers of the pathogenic PLN p.Arg14del variant, 18 cases with other pathogenic or likely pathogenic variants in cardiomyopathy-related genes, and 3 with only variants of unknown significance). Immunohistochemical analysis revealed typical dense perinuclear globular PLN-positive aggregates, representing aggresomes, in all nine PLN p.Arg14del cases. In 20 non-PLN cases, PLN-staining was absent. In one non-PLN case, one of the two independent observers misinterpreted PLN staining of heavily wrinkled nuclear membranes of cardiomyocytes as perinuclear PLN aggregates. In this genetic cardiomyopathy cohort, PLN Immunohistochemical analysis in LVAD biopsies was found to be a highly sensitive (100%) and specific (95%) method for demonstration of PLN protein aggregates in PLN p.Arg14del cardiomyopathy. In clinical practice, PLN immunohistochemical analysis of LVAD specimens can be of incremental value in the diagnostic workup of this cardiomyopathy, even more so if genetic analysis is not readily available.


Assuntos
Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/genética , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/genética , Imuno-Histoquímica/métodos , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Sequência de Aminoácidos , Displasia Arritmogênica Ventricular Direita/metabolismo , Biópsia , Cardiomiopatia Dilatada/metabolismo , Testes Genéticos , Variação Genética , Coração Auxiliar , Heterozigoto , Humanos , Imuno-Histoquímica/estatística & dados numéricos , Miócitos Cardíacos/metabolismo , Agregação Patológica de Proteínas/genética , Agregação Patológica de Proteínas/metabolismo , Deleção de Sequência
20.
J Cutan Pathol ; 44(11): 931-937, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28749576

RESUMO

Muir-Torre syndrome is a clinical variant of Lynch syndrome defined by the synchronous or metachronous occurrence of at least one sebaceous neoplasm and at least one Lynch syndrome-related internal cancer. Although screening guidelines for patients with colorectal carcinomas have been established, screening guidelines for cutaneous Muir-Torre associated neoplasms are not currently available. As such, we reviewed the current evidence for the use of MLH1, MSH2, MSH6 and PMS2 immunohistochemistry when cutaneous Muir-Torre associated neoplasms are encountered. We identified weak to moderate support overall for the global use of these assays, with some evidence suggesting a tailored approach using clinical parameters as an adjunct. We also assessed the current utilization patterns of attendees of the American Society of Dermatopathology Annual Meeting (Chicago, 2016). We found that 91% of respondents utilize mismatch repair immunohistochemistry, with the majority utilizing these tests only when requested by the submitting clinician.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/diagnóstico , Reparo de Erro de Pareamento de DNA , Síndrome de Muir-Torre/complicações , Neoplasias das Glândulas Sebáceas/diagnóstico , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Enzimas Reparadoras do DNA/genética , Humanos , Imuno-Histoquímica/estatística & dados numéricos , Síndrome de Muir-Torre/genética , Neoplasias das Glândulas Sebáceas/etiologia , Neoplasias das Glândulas Sebáceas/genética
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