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1.
Int J Gynecol Pathol ; 41(3): 298-306, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35444146

RESUMO

Accurate diagnosis of differentiated vulvar intraepithelial neoplasia (dVIN) is challenging, in part due to the sometimes subtle nature of its atypia. Many dVIN lesions demonstrate aberrant p53 staining; however, staining patterns overlap between dVIN and benign/reactive entities. We evaluate a p53/CK17 dual stain in an initial cohort of dVIN (n=30), benign vulvar skin (n=5), lichen sclerosus (LS, n=10), lichen simplex chronicus (LSC, n=10), and pseudoepitheliomatous hyperplasia (PEH, n=10). In the initial cohort, aberrant p53 staining was seen only in dVIN (50%, 15/30). Equivocal p53 staining patterns were seen in dVIN (37%, 11/30), LS (50%, 5/10), LSC (40%, 4/10), and PEH (40%, 4/10). All 30 dVIN cases were positive for CK17 (strong partial-thickness or full-thickness staining), but positive CK17 staining was also seen in LS (70%, 7/10), LSC (50%, 5/10), and PEH (100%, 10/10). In the initial cohort, the combination of aberrant p53 and positive CK17 was seen only for dVIN (50%, 15/30). Forty cases of LS with known follow-up (20 with progression to dVIN, 20 without) were stained to assess prognostic value. Three LS cases showed aberrant p53 staining with CK17 positivity; all progressed to dVIN. Equivocal p53 staining and CK17 positivity were seen in cases with and without progression. The p53/CK17 dual stain is more diagnostically useful than either stain alone. Negative/focal staining for CK17 argues against a diagnosis of dVIN, while aberrant p53 staining with CK17 positivity strongly supports the diagnosis.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Lesões Intraepiteliais Escamosas , Proteína Supressora de Tumor p53/metabolismo , Líquen Escleroso Vulvar , Neoplasias Vulvares , Biomarcadores Tumorais , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Corantes , Feminino , Humanos , Líquen Escleroso Vulvar/patologia , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/patologia
2.
Pathol Res Pract ; 233: 153877, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35398619

RESUMO

BACKGROUND: The expression status of HER2 is an important factor in evaluating the prognosis of breast cancer. We found that the positivity rate of HER2 varied with the diameter of invasive lesions in early breast cancer.We aimed to explore the relationship between the change of HER2 positivity rate of early breast cancer and the diameter of the invasive foci and its clinical significance. METHODS: A total of 217 patients with microinvasive breast cancer and T1a stage breast cancer were enrolled in this study. Machine learning algorithm was used to extract morphological features of invasive lesions in early breast cancer. Using Spearman to analysis the clinicopathological and morphological features related to HER2 expression McNemar test was used to analyze the consistency of HER2 expression between the carcinoma in situ area and the invasive cancer area. RESULTS: In early breast cancer, the diameter of the invasive foci was strongly negatively correlated with the expression status of HER2 (rho=-0.468, p < 0.001). As the diameter of the invasive foci increases, the HER2 positivity rate gradually decreases. When the diameter of the invasive foci> 2 mm, the positivity rate of HER2 was significantly reduced (from 52.6% to 16.1%, p < 0.001), which was close to the positivity rate of HER2 in ordinary invasive breast cancer. Moreover, most of the clinicopathological characteristics of breast cancer with an invasive lesion diameter of 1-2 mm and DCIS-MI were not significantly different (p > 0.05). Among 217 patients, the consistency rate of HER2 expression in carcinoma in situ and invasive foci areas was 97.7% (212/217), and there was no significant difference in HER2 expression status (p = 0.25 and p = 0.50, respectively). CONCLUSIONS: We recommend that breast cancer with an invasive lesion diameter of 1-2 mm should be classified as microinvasive breast cancer. In early breast cancer,the expression status of HER2 in the invasive foci area can refer to the HER2 expression status in carcinoma in situ area. However, it needs further support from a large amount of data and follow-up results.


Assuntos
Neoplasias da Mama , Carcinoma in Situ , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Prognóstico , Receptor ErbB-2/metabolismo
3.
Diagn Cytopathol ; 50(6): 289-294, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35262275

RESUMO

BACKGROUND: The role of urinary cytology as a diagnostic test for the detection and surveillance of urothelial cancer is crucial. Intravesical bacillus Calmette-Guerin (BCG) is the appropriate therapeutic strategy for patients with high-grade urothelial carcinoma (HGCU) or in situ carcinoma. We investigate how applicable is the Paris System for reporting urinary cytology (TPS) and how accurate is urinary cytology, in patients who undergo intravesical BCG instillations. METHODS: Our study contains urine samples from patients during the period January 1, 2017 to December 31, 2019. The inclusion criteria were patients with history of urothelial bladder carcinoma who had been treated with intravesical BCG instillation and cytology was followed by histology. We report our results and estimate the risk of high-grade malignancy (ROHM) for each TPS category and cytology accuracy. RESULTS: Four hundred thirty-eight samples corresponding to 146 patients fulfilled the criteria to be included in the study. There were 2 inadequate, 118 negative for high-grade urothelial carcinoma (NHGUC), 14 atypical urothelial cells (AUC), 6 suspicious for high-grade urothelial carcinoma (SHGUC), and 6 cases HGUC. Corresponding histology assessment has shown that the ROHM amounted to 0 for inadequate, 3.4% for NHGUC, 57% for AUC, 100% for SHGUC and HGUC. Sensitivity was 50%, specificity 100%, PPV 100%, NPV 91%, and accuracy 91.7%, considering inadequate, NHGUC and AUC as negative and SHGUC and HGUC as positive result. However, considering AUC a positive result, the accuracy parameters were different; sensitivity 83.3%, specificity 95%, PPV 76.9%, NPV 96.67%, and accuracy 93%. CONCLUSION: The Paris system for reporting urinary cytology can be safely applied to patients during follow-up after BCG intravesical administration.


Assuntos
Carcinoma in Situ , Carcinoma de Células de Transição , Mycobacterium bovis , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Vacina BCG/uso terapêutico , Carcinoma in Situ/patologia , Carcinoma de Células de Transição/diagnóstico , Citodiagnóstico/métodos , Feminino , Humanos , Masculino , Neoplasias da Bexiga Urinária/patologia , Urina , Neoplasias Urológicas/patologia , Urotélio/patologia
4.
Cancer Res ; 82(9): 1803-1817, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35247892

RESUMO

Biliary cancer has long been known to carry a poor prognosis, yet the molecular pathogenesis of carcinoma of the extrahepatic biliary system and its precursor lesions remains elusive. Here we investigated the role of Kras and canonical Wnt pathways in the tumorigenesis of the extrahepatic bile duct (EHBD) and gall bladder (GB). In mice, concurrent activation of Kras and Wnt pathways induced biliary neoplasms that resembled human intracholecystic papillary-tubular neoplasm (ICPN) and biliary intraepithelial neoplasia (BilIN), putative precursors to invasive biliary cancer. At a low frequency, these lesions progressed to adenocarcinoma in a xenograft model, establishing them as precancerous lesions. Global gene expression analysis revealed increased expression of genes associated with c-Myc and TGFß pathways in mutant biliary spheroids. Silencing or pharmacologic inhibition of c-Myc suppressed proliferation of mutant biliary spheroids, whereas silencing of Smad4/Tgfbr2 or pharmacologic inhibition of TGFß signaling increased proliferation of mutant biliary spheroids and cancer formation in vivo. Human ICPNs displayed activated Kras and Wnt signals and c-Myc and TGFß pathways. Thus, these data provide direct evidence that concurrent activation of the Kras and canonical Wnt pathways results in formation of ICPN and BilIN, which could develop into biliary cancer. SIGNIFICANCE: This work shows how dysregulation of canonical cell growth pathways drives precursors to biliary cancers and identifies several molecular vulnerabilities as potential therapeutic targets in these precursors to prevent oncogenic progression.


Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Carcinoma in Situ , Lesões Pré-Cancerosas , Animais , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Pigmentos Biliares/metabolismo , Neoplasias do Sistema Biliar/genética , Carcinoma in Situ/patologia , Humanos , Camundongos , Lesões Pré-Cancerosas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Via de Sinalização Wnt/genética
5.
Mol Med Rep ; 25(5)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35266015

RESUMO

Presence of nuclear atypia during histological investigation is often a cause of concern for pathologists while identifying tumor and non­tumor cells in a biopsy sample of oral mucosa. Nuclear atypia is observed in severe inflammation, ulcers and reactive changes. Therefore, additional methods, such as immunohistochemistry, may help precise diagnosis. When the atypia is suggestive of tumorous or reactive origin, the lesion is diagnosed as atypical squamous epithelium (ASE). When there is severe nuclear atypia in the mucosa, such as in disorders of nuclear polarity, large nuclei, and clear nucleolus, the lesion is diagnosed as carcinoma in situ (CIS). However, it is not easy to distinguish ASE and CIS using hematoxylin and eosin staining. The present study aimed to distinguish ASE from CIS using immunohistochemistry. A total of 32 biopsy samples of either ASE or CIS cases were selected and the level of casein kinase 1ε (CK­1ε), differentiated embryonic chondrocyte gene 1 (DEC1), proliferating cell nuclear antigen (PCNA) and CD44, which are four protein markers which have been previously linked to cancer progression, were analyzed. CK­1ε and CD44 expression was higher in CIS samples than in ASE samples. However, DEC1 expression was lower in CIS samples than in ASE samples. PCNA expression was not markedly different between the two groups. Additionally, it was found that DEC1­overexpressing cells had decreased levels of CK­1ε and CD44 compared with control cells, while CK­1ε­overexpressing cells had relatively unchanged levels of CD44, DEC1 and PCNA. These results suggested that DEC1 negatively regulates the expression of CK­1ε and CD44. Thus, DEC1, CK­1ε, and CD44 were identified as mechanistically linked and clinically relevant protein biomarkers, which could help distinguish ASE and CIS.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Proteínas Supressoras de Tumor/metabolismo , Biomarcadores Tumorais , Carcinoma in Situ/patologia , Carcinoma de Células Escamosas/patologia , Caseína Quinases , Epitélio/patologia , Humanos , Receptores de Hialuronatos , Imuno-Histoquímica
6.
J Low Genit Tract Dis ; 26(2): 140-146, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35249976

RESUMO

OBJECTIVE: Vulvar intraepithelial neoplasia (VIN) is a premalignant condition with high recurrence rates despite treatment. Vulvar intraepithelial neoplasia develops through separate etiologic pathways relative to the presence or absence of human papillomavirus (HPV) and TP53 mutations. This systematic review was conducted (1) to identify historical risk factors for the development, recurrence, and progression of VIN and (2) to critique these risk factors in the context of advances made in the stratification of VIN based on HPV or TP53 status. MATERIALS AND METHODS: A systematic search was performed on MEDLINE, Embase, Cochrane Database, PsychInfo, and CINAHL from inception to July 5, 2021. Three gynecologic oncologists independently evaluated the eligibility of studies based on predetermined inclusion and exclusion criteria, abstracted data, and then analyzed the relevant data. RESULTS: A total of 1,969 studies (involving 6,983 patients) were identified. Twenty-nine studies met inclusion criteria. The quality of evidence was low; primarily level 2b (Oxford Centre for Evidence-Based Medicine). Risk factors associated with the development of VIN include: smoking and coexisting vulvar dermatoses. Risk factors associated with recurrence include: smoking, multifocal disease, and positive surgical margins. Recent studies identified the presence of differentiated VIN/TP53 mutation as the most significant risk factor for both VIN recurrence and malignant progression. CONCLUSIONS: The current body of evidence consists primarily of small retrospective observational studies. Well-designed retrospective case-control series and/or prospective observational studies are urgently needed. Ideally, future studies will collect standardized data regarding associated risk factors and stratify women with VIN based on HPV and TP53 status.


Assuntos
Carcinoma in Situ , Infecções por Papillomavirus , Neoplasias Vulvares , Carcinoma in Situ/patologia , Feminino , Humanos , Estudos Observacionais como Assunto , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Vulvares/patologia
7.
Acta Gastroenterol Belg ; 85(1): 108-110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35305003

RESUMO

Anal intraepithelial neoplasia is a premalignant lesion for anal squamous cell carcinoma. Current treatment options, consisting of topical therapy and local ablative procedures with electrocautery or radiofrequency ablation, are effective although recurrence rates are high. Experience with endoscopic submucosal dissection for anal lesions is limited, with only a few cases of anal intraepithelial neoplasia and early anal squamous cell carcinoma. We present a 65-year-old woman with high-grade anal intraepithelial neoplasia successfully removed by endoscopic submucosal dissection with no complications or signs of recurrence after 5 months, suggesting that this technique could be a safe and effective approach for management of anal premalignant lesions.


Assuntos
Neoplasias do Ânus , Carcinoma in Situ , Carcinoma de Células Escamosas , Ressecção Endoscópica de Mucosa , Lesões Pré-Cancerosas , Idoso , Neoplasias do Ânus/complicações , Neoplasias do Ânus/patologia , Neoplasias do Ânus/cirurgia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma in Situ/cirurgia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Lesões Pré-Cancerosas/cirurgia
8.
J Low Genit Tract Dis ; 26(2): 147-151, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35238809

RESUMO

OBJECTIVES: The aim of the study were to identify the risk factors for recurrent vaginal intraepithelial neoplasia (VaIN)1+ and to evaluate the efficacy of laser vaporization in patients who underwent hysterectomy for the treatment of cervical intraepithelial neoplasia (CIN). METHODS: Medical records of 374 women who underwent hysterectomy for the treatment of CIN were retrospectively reviewed. Recurrence was defined as VaIN1+ diagnosis by colposcopy-directed biopsy. RESULTS: Among 374 patients, 36 (9.6%) had VaIN1+ during a median follow-up of 32 (0-193) months: 13 (3.5%) had VaIN1, 6 (1.6%) VaIN2, 15 (4.0%) VaIN3, and 2 (0.5%) invasive cancer. Multivariate analysis showed that age of greater than 50 years was the only independent risk factor for VaIN1+ recurrence (odds ratio, 3.359; 95% CI, 1.60-7.07; p = .001). Among the 34 patients with VaIN, 21 (61.8%) were treated with laser vaporization and 11 (32.3%) were observed without treatment. Time to second recurrence was longer in the VaIN treated by laser vaporization group than that in the observation group (mean time to subsequent recurrence, 128.7 [95% CI, 101.4-156.0] vs. 41.8 [15.7-67.9] months; p = .003). Moreover, laser vaporization (hazard ratio, 0.125; 95% CI, 0.03-0.59; p = .009) was the only independent good prognostic factor for the second VaIN1+ recurrence. CONCLUSIONS: Patients older than 50 years who underwent hysterectomy for the treatment of CIN might be highly at risk of VaIN1+. Laser vaporization is the only independent prognostic factor that might prevent the second VaIN1+ recurrence.


Assuntos
Carcinoma in Situ , Neoplasia Intraepitelial Cervical , Neoplasias do Colo do Útero , Neoplasias Vaginais , Carcinoma in Situ/patologia , Neoplasia Intraepitelial Cervical/patologia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/diagnóstico , Neoplasias Vaginais/patologia
9.
Surg Pathol Clin ; 15(1): 95-103, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35236636

RESUMO

As the first node in treatment algorithms for breast disease, pathologists have the potential to play a critical role in refining appropriate therapy for lesions in the atypical ducal hyperplasia-ductal carcinoma in situ (ADH-DCIS) spectrum by conservatively approaching diagnosis of lesions limited in size on core needle biopsy. Appropriate efforts to downgrade the diagnosis of lesions at the borderline of ADH and DCIS will certainly lead to more breast conservation and avoid the common morbidities of mastectomy, sentinel node biopsy, and radiation therapy. Whether results of clinical trials of active surveillance will successfully identify a subset of women who may successfully forgo even limited breast-conserving surgery is eagerly anticipated. Given the increasing concern that a significant number of women with DCIS are overtreated, identification of patients at very low risk for progression who may forgo surgery and radiation therapy safely is of significant interest.


Assuntos
Neoplasias da Mama , Carcinoma in Situ , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Carcinoma in Situ/diagnóstico , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/terapia , Feminino , Humanos , Hiperplasia/diagnóstico , Mastectomia
10.
Gynecol Oncol ; 165(1): 114-120, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35123772

RESUMO

OBJECTIVE: To determine the activity of key signal transduction pathways in serous tubal intraepithelial carcinoma (STIC) and concurrent high-grade serous carcinoma (HGSC) and compare this to pathway activity in normal Fallopian tube epithelium (FTE). METHODS: We assessed mRNA expression levels of pathway-specific target genes with RT-qPCR in STIC and concurrent HGSC (n = 8) and normal FTE (n = 8). Subsequently, signal transduction pathway assays were used to assess functional activity of the androgen (AR) and estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor beta (TGF-ß) and canonical wingless-type MMTV integration site (Wnt) pathways. RESULTS: There were no statistically significant differences in pathway activity between STIC and HGSC, but STIC and HGSC demonstrated significantly lower ER and higher PI3K and HH pathway activity in comparison to normal FTE, suggesting these pathways as putative early drivers. In addition, we determined FOXO3a protein expression by immunohistochemistry and found loss of FOXO3a protein expression in STIC and HGSC compared to normal FTE. This observation confirmed that activation of PI3K signaling by loss of FOXO is an early hallmark of serous carcinogenesis. Furthermore, HGSC demonstrated significant loss of AR and Wnt pathway activity in relation to FTE, suggesting these pathways contribute to disease progression. CONCLUSION: Our observations, together with the previously described associations between p53 signaling and both PI3K and HH pathway activity, provide evidence that increased PI3K and HH pathway activity and loss of ER pathway activity may be underlying events contributing to neoplastic transformation of FTE into STIC.


Assuntos
Adenocarcinoma in Situ , Carcinoma in Situ , Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Adenocarcinoma in Situ/patologia , Carcinoma in Situ/patologia , Cistadenocarcinoma Seroso/patologia , Epitélio/metabolismo , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/patologia , Feminino , Proteínas Hedgehog , Humanos , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais
11.
Int J Clin Oncol ; 27(5): 958-968, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35142962

RESUMO

BACKGROUND: This study investigated the clinical impact of carcinoma in situ (CIS) in intravesical Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: This study retrospectively evaluated 3035 patients who were diagnosed with NMIBC and treated by intravesical BCG therapy between 2000 and 2019 at 31 institutions. Patients were divided into six groups according to the presence of CIS as follows: low-grade Ta without concomitant CIS, high-grade Ta without concomitant CIS, high-grade Ta with concomitant CIS, high-grade T1 without concomitant CIS, high-grade T1 with concomitant CIS, and pure CIS (without any papillary lesion). The endpoints were recurrence- and progression-free survival after the initiation of BCG therapy. We analyzed to identify factors associated with recurrence and progression. RESULTS: At a median follow-up of 44.4 months, recurrence and progression were observed in 955 (31.5%) and 316 (10.4%) patients, respectively. Comparison of six groups using univariate and multivariate analysis showed no significant association of CIS. However, CIS in the prostatic urethra was an independent factors associated with progression. CONCLUSION: Concomitant CIS did not show a significant impact in the analysis of Ta and T1 tumors which were treated using intravesical BCG. Concomitant CIS in the prostatic urethra was associated with high risk of progression. Alternative treatment approaches such as radical cystectomy should be considered for patients with NMIBC who have a risk of progression.


Assuntos
Carcinoma in Situ , Neoplasias da Bexiga Urinária , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/patologia , Cistectomia , Feminino , Humanos , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia
12.
Sci Rep ; 12(1): 2570, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35173208

RESUMO

A large proportion of colorectal carcinomas (CRC) evolve from colorectal adenomas. However, not all individuals with colonic adenomas have a risk of CRC substantially higher than those of the general population. The aim of the study was to determine the differences or similarities of mutation profile among low- and high-grade adenomas and in situ carcinoma with detailed follow up. We have investigated the mutation spectrum of well-known genes involved in CRC (such as APC, BRAF, EGFR, NRAS, KRAS, PIK3CA, POLE, POLD1, SMAD4, PTEN, and TP53) in a large, well-defined series of 96 adenomas and in situ carcinomas using a high-throughput genotyping technique. Besides, the microsatellite instability and APC and MLH1 promoter methylation were studied as well. We observed a high frequency of pathogenic variants in the studied genes. The APC, KRAS and TP53 mutation frequencies were slightly lower in adenoma samples than in in situ carcinoma samples. Further, when we stratified mutation frequency based on the grade, the frequency distribution was as follows: low-grade adenoma-high-grade adenomas-in situ carcinoma: APC gene 42.9-56.0-54.5%; KRAS gene 32.7-32.0-45.5%; TP53 gene 8.2-20.0-18.2%. The occurrence of KRAS mutation was associated with the presence of villous histology and methylation of the APC promoter was significantly associated with the presence of POLE genetic variations. However, no association was noticed with the presence of any singular mutation and occurrence of subsequent adenoma or CRC. Our data supports the multistep model of gradual accumulation of mutations, especially in the driver genes, such as APC, TP53 and KRAS.


Assuntos
Adenoma/patologia , Biomarcadores Tumorais/genética , Carcinoma in Situ/patologia , Neoplasias Colorretais/patologia , Instabilidade de Microssatélites , Mutação , Adenoma/genética , Idoso , Carcinoma in Situ/genética , Neoplasias Colorretais/genética , Metilação de DNA , Feminino , Seguimentos , Humanos , Masculino , Prognóstico
15.
Oncogene ; 41(10): 1507-1517, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35082384

RESUMO

Molecular events occurring in stepwise progression from pre-malignant lesions (pancreatic intraepithelial neoplasia; PanIN) to the development of pancreatic ductal adenocarcinoma (PDAC) are poorly understood. Thus, characterization of early PanIN lesions may reveal markers that can help in diagnosing PDAC at an early stage and allow understanding the pathology of the disease. We performed the molecular and histological assessment of patient-derived PanINs, tumor tissues and pancreas from mouse models with PDAC (KC mice that harbor K-RAS mutation in pancreatic tissue), where we noted marked upregulation of gastrokine (GKN) proteins. To further understand the role of gastrokine proteins in PDAC development, GKN-deficient KC mice were developed by intercrossing gastrokine-deficient mice with KC mice. Panc-02 (pancreatic cancer cells of mouse origin) were genetically modified to express GKN1 for further in vitro and in vivo analysis. Our results show that gastrokine proteins were absent in healthy pancreas and invasive cancer, while its expression was prominent in low-grade PanINs. We could detect these proteins in pancreatic juice and serum of KC mice. Furthermore, accelerated PanIN and tumor development were noted in gastrokine deficient KC mice. Loss of gastrokine 1 protein delayed apoptosis during carcinogenesis leading to the development of desmoplastic stroma while loss of gastrokine 2 increased the proliferation rate in precursor lesions. In summary, we identified gastrokine proteins in early pancreatic precursor lesions, where gastrokine proteins delay pancreatic carcinogenesis.


Assuntos
Carcinoma in Situ , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Hormônios Peptídicos , Animais , Carcinogênese , Carcinoma in Situ/genética , Carcinoma in Situ/metabolismo , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Humanos , Camundongos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia
16.
Indian J Pathol Microbiol ; 65(1): 149-151, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35074982

RESUMO

BACKGROUND: Cystic Hypersecretory Carcinoma (CHC) is a rare subset of breast carcinoma. It is part of a spectrum of cystic hypersecretory lesions which includes cystic hypersecretory hyperplasia (CHH), CHH with atypia, CHC in situ and CHC with invasion. Approximately 65 cases of cystic hypersecretory lesions have been reported; most of them were CHC in situ and only 19 cases of CHC with invasion have been reported so far. CASE PRESENTATION: We are reporting 2 cases of 47 and 62 year old women with a palpable breast mass for 6 and 1 month duration respectively. Trucut biopsy was carried out for both which showed high grade ductal carcinoma in situ with microinvasion in the first patient and the latter showed a tiny focus of invasive carcinoma. Simple mastectomy and modified radical mastectomy (MRM) were done for the respective cases; both showed dilated cystic spaces filled with eosinophilic secretions (thyroid colloid-like), lining neoplastic cells that showed variable degrees of proliferation, atypia and in situ carcinoma. There were foci of invasion in both cases and hence a morphological diagnosis of CHC with invasion was made. CONCLUSION: Owing to a smaller number of reported cases, little is known about the biological behavior, prognosis and molecular profile of cystic hypersecretory carcinoma.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/secundário , Mama/patologia , Carcinoma/diagnóstico por imagem , Carcinoma/secundário , Biópsia , Mama/diagnóstico por imagem , Neoplasias da Mama/classificação , Neoplasias da Mama/cirurgia , Carcinoma in Situ/patologia , Feminino , Técnicas Histológicas , Humanos , Mastectomia , Pessoa de Meia-Idade
17.
BMC Cancer ; 22(1): 120, 2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35093004

RESUMO

BACKGROUND: Endoscopic treatment methods for early colorectal cancer (ECRC) mainly depend on the size and morphology. It is unclear whether different endoscopic resection methods could achieve curative resection for ECRC confined in the mucosa. The study was designed to compare the rate of positive vertical margin (VM) of ECRC with advanced adenomas (AAs) including adenoma > 1 cm, villous adenoma, high-grade intraepithelial neoplasia/dysplasia stratified by different endoscopic resection methods. METHODS: Rate of positive VM for 489 ECRCs including Intramucosal (pTis) and superficial submucosal invasion (pT1) carcinomas were compared with those of 753 AAs stratified by different endoscopic resection methods using Chi-squared test. Multivariate logistic model was performed to investigate the risk factors of positive VM for different endoscopic resection methods. RESULTS: The pTis ECRC exhibited a similar rate of positive VM as that of AAs for en bloc hot snare polypectomy (HSP, 0% Vs. 0.85%, P = 0.617), endoscopic mucosal resection (EMR, 0.81% vs. 0.25%, P = 0.375) and endoscopic submucosal dissection (ESD, 1.82% Vs. 1.02%, P = 0.659). The pTis carcinoma was not found to be a risk factor for positive VM by en bloc EMR (P = 0.349) or ESD (P = 0.368). The en bloc resection achieved for pT1a carcinomas exhibited similar to positive VM achieved through ESD (2.06% Vs. 1.02%, P = 1.000) for AAs. Nonetheless, EMR resulted in higher risk of positive VM (5.41% Vs. 0.25%, P < 0.001) for pT1a carcinomas as compared to AAs. The pT1a invasion was identified as a risk factor for positive VM in polyps with en bloc EMR (odds ratio = 23.90, P = 0.005) but not ESD (OR = 2.96, P = 0.396). CONCLUSION: Collectively, the pTis carcinoma was not found to be a risk factor for positive VM resected by en bloc HSP, EMR or ESD. Additionally, ESD may be preferred over EMR for pT1a carcinomas with lower rate of positive VM.


Assuntos
Adenoma/cirurgia , Carcinoma in Situ/cirurgia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/estatística & dados numéricos , Mucosa Intestinal/cirurgia , Adenoma/patologia , Idoso , Carcinoma in Situ/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Mucosa Intestinal/patologia , Modelos Logísticos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Histopathology ; 80(5): 820-826, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35038193

RESUMO

AIMS: In-situ follicular neoplasia (ISFN) is a histologically recognizable neoplastic proliferation of follicular lymphoma (FL)-like B cells confined to the germinal centres. While some ISFNs are associated with overt FL, others are incidentally identified as isolated or pure forms in individuals without evidence of overt FL. The prevalence of incidentally found isolated ISFN is approximately 3% in Europe; however, no screening study has been conducted in Asia. To investigate the incidence and clinicopathological characteristics of ISFNs in the Japanese population, we conducted histopathological screening of the lymph nodes (LNs) resected for solid tumours or inflammatory conditions. METHODS AND RESULTS: We screened for ISFN in 5700 LNs from 340 individuals using immunohistochemistry for BCL2 and identified seven ISFNs, with an incidence of 2.1%. The median age of the individuals with ISFN was 67 years, none of whom developed overt FL, with a median follow-up of 59 months. Next-generation sequencing was performed in five ISFNs, and 10 variants in seven FL-associated genes were identified. The identified variants included HIST1H1E (n = 2), ARID1A (n = 2), KMT2D (n = 1), CARD11 (n = 1), BCL7A (n = 1), CREBBP (n = 1) and TNFRSF14 (n = 1). CONCLUSIONS: The incidence of isolated ISFN in the Japanese population is not significantly different from that in Europe, presumably reflecting the recent increase in FL in Japan. These incidentally found ISFNs have a low potential to transform into overt FL. Although mutations of FL-associated genes are already present in ISFNs, further molecular studies are needed to identify driver genes leading to the transformation of ISFN to overt FL.


Assuntos
Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Detecção Precoce de Câncer , Linfoma Folicular/genética , Linfoma Folicular/patologia , Idoso , Carcinoma in Situ/epidemiologia , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Incidência , Japão/epidemiologia , Linfonodos/patologia , Linfoma Folicular/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
19.
Breast Dis ; 41(1): 215-219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35094985

RESUMO

We report three cases of focally thickened ductal lesions found on screening ultrasonography with fine needle aspiration (FNA)-proven benign cytology in order to demonstrate the different fates of this radiographic finding. All three patients, aged 74, 69 and 68 years old, had their first time mammography and concurrent ultrasonography. Their mammograms did not show abnormalities except a focal asymmetry in one case. The sonographic focally thick ducts were the lesions of concern and all the patients had long-term follow-up.One patient had a slightly decreased lesion size on follow-up, likely to be a non-proliferative alteration of the breast. One patient's FNA revealed a benign papillary lesion whose ductal diameter slightly increased in size with internal echo after two years with repeat FNA demonstrating epithelial papillae consistent with intraductal papilloma. The final patient had an alteration of the imaged ductal lesion in the third year of follow-up and the final specimen after surgical wide excision that was done in the fourth year confirmed cancer. We emphasize the importance of focally thickened ductal lesions found on screening sonography and underscore their need for scrutinized characterization and long term follow-up.


Assuntos
Glândulas Mamárias Humanas/diagnóstico por imagem , Ultrassonografia , Idoso , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Mamografia , Papiloma Intraductal/patologia
20.
Clin Genitourin Cancer ; 20(2): e166-e172, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35033480

RESUMO

INTRODUCTION: The aim of this multicenter study was to investigate the role of age (cut-off 70 years) at diagnosis in predicting oncologic behavior of pure carcinoma in situ of the bladder. MATERIAL AND METHODS: Inclusion criteria were: patients with pure CIS confirmed and that followed intravesical BCG treatment. Pure CIS was defined at any CIS not associated with another urothelial cancer. Exclusion criteria were: any CIS associated with invasive urothelial carcinoma. A total of 172 with pure CIS treated between January 1, 2002 and December 31, 2012 at 8 academic institutions met the inclusion criteria. The maintenance schedule was generally according to the EAU guidelines at the time RESULTS: A total of 99 (57.6%) patients had an age >70 years prior to TURBT. There was no difference between clinico-pathologic features among groups (group 1, age ≤ 70 years and group 2, age > 70 years), except that patients aged ≤ 70 years presented a larger size of CIS (35.6% vs. 21.2%), P = .02. In multivariable Cox regression analyses, the same clinico-pathologic factors (age, multifocality, and recurrent tumor state) were independently associated with worse RFS. Harrell's C-index was 65.75.In multivariable Cox regression analyses in addition to age (P = .006) and multifocality (P < .001) also BMI (P = .04) was independently associated with worse PFS. Harrell's C-index was 74.71 CONCLUSION: Advanced age at diagnosis appears to be associated with an increased risk of recurrence and progression of pure carcinoma in situ of the bladder. Elderly patients might fail to respond to BCG therapy.


Assuntos
Carcinoma in Situ , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Idoso , Vacina BCG/uso terapêutico , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/terapia , Estudos de Coortes , Progressão da Doença , Humanos , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia
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