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1.
Tumour Biol ; 46(1): 1-11, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728194

RESUMO

BACKGROUND: It is well established that most colorectal carcinomas arise from conventional adenomas through the adenoma-carcinoma sequence (ACS) model. mitogen-activated protein kinases (MAPKs) pathway has been reported as a crucial player in tumorigenesis. The MAPK signaling pathway is activated by different extracellular signals involving the "mitogen-activated/extracellular signal-regulated kinase 1 (MEK1)", and this induces the expression of genes involved in proliferation and cellular transformation. Diaphanous-related formin-3 (DIAPH3) acts as a potential metastasis regulator through inhibiting the cellular transition to amoeboid behavior in different cancer types. OBJECTIVE: The aim of the study was to investigate the pattern of immunohistochemical expression of MEK1 and DIAPH3 in colorectal adenoma (CRA) and corresponding colorectal carcinoma (CRC) specimens. METHODS: The immunohistochemical expression of DIAPH3 and MEK1 was examined in 43 cases of CRC and their associated adenomas using tissue microarray technique. RESULTS: MEK1 was overexpressed in 23 CRC cases (53.5%) and in 20 CRA cases (46.5%). DIAPH3 was overexpressed in 11 CRA cases (about 29%) which were significantly lower than CRC (22 cases; 58%) (P = 0.011). Both MEK1 and DIAPH3 overexpression were significantly correlated in CRC (P = 0.009) and CRA cases (P = 0.002). Tumors with MEK1 overexpression had a significantly higher tumor grade (P = 0.050) and perineural invasion (P = 0.017). CONCLUSIONS: Both MEK1 and DIAPH3 are overexpressed across colorectal ACS with strong correlation between them. This co- expression suggests a possible synergistic effect of MEK1 and DIAPH-3 in colorectal ACS. Further large-scale studies are required to investigate the potential functional aspects of MEK1 and DIAPH3 in ACS and their involvement in tumor initiation and the metastatic process.


Assuntos
Adenoma , Neoplasias Colorretais , Forminas , MAP Quinase Quinase 1 , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Forminas/genética , Forminas/metabolismo , Adenoma/patologia , Adenoma/genética , Adenoma/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , MAP Quinase Quinase 1/genética , MAP Quinase Quinase 1/metabolismo , Adulto , Imuno-Histoquímica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Carcinoma/patologia , Carcinoma/genética , Carcinoma/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética
2.
BMC Cancer ; 24(1): 577, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730358

RESUMO

BACKGROUND: Soft-tissue metastasis of carcinoma is rare. In the present study, we investigated the surgical indications and clinical features of patients with soft tissue metastases of carcinoma. METHODS: In this retrospective cohort study, we enrolled 26 patients with soft tissue carcinoma metastasis referred to our department for treatment. Sex, age, location, size, depth, pain due to the tumor, primary origin, serum C-reactive protein (CRP) level, MRI examinations, diagnosis by a previous physician, carcinoma markers from blood, history of carcinoma, other metastases, performance status (PS), and surgical procedures were documented. Associations between variables and surgery were statistically analyzed. RESULTS: The primary cancer origin was found to be the lung (n = 10), kidney (n = 7), esophagus (n = 2), stomach (n = 1), breast (n = 1), liver (n = 1), ureter (n = 1), anus (n = 1), and unknown (n = 2). The mean CRP level of all patients was 2.3 mg/dL. Seven tumors (26.9%) were originally suspected to be soft tissue metastases of carcinoma, while 19 tumors (73.1%) were considered soft tissue sarcomas or inflammatory lesions by the previous treating physician. Twenty patients (76.9%) had other metastases. The PS of the 12 patients (46.2%) was zero. Eleven patients (42.3%) underwent surgery for soft tissue metastases. Diagnosis of soft tissue metastasis by a previous physician and good PS (p < 0.05) were significantly associated with surgery. CONCLUSION: Overall, the present results show that surgical indications for soft tissue metastasis of carcinoma include diagnosis by the referring physician or good PS of the patients.


Assuntos
Neoplasias de Tecidos Moles , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Neoplasias de Tecidos Moles/cirurgia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/secundário , Adulto , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Carcinoma/cirurgia , Carcinoma/sangue , Carcinoma/patologia , Carcinoma/secundário , Imageamento por Ressonância Magnética
3.
Nat Commun ; 15(1): 3736, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744818

RESUMO

The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA-directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines. PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. PIAS2b depletion promotes mitotic catastrophe at prophase. High-throughput proteomics reveals the proteasome (PSMC5) and spindle cytoskeleton (TUBB3) to be direct targets of PIAS2b SUMOylation at mitotic initiation. These results identify PIAS2b-dsRNAi as a promising therapy for ATC and other aggressive anaplastic carcinomas.


Assuntos
Mitose , Proteínas Inibidoras de STAT Ativados , Humanos , Proteínas Inibidoras de STAT Ativados/metabolismo , Proteínas Inibidoras de STAT Ativados/genética , Animais , Linhagem Celular Tumoral , Camundongos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Interferência de RNA , Fuso Acromático/metabolismo , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Complexo de Endopeptidases do Proteassoma/metabolismo , Sumoilação , Carcinoma/genética , Carcinoma/metabolismo , Carcinoma/patologia , Feminino
4.
Zhonghua Yi Xue Za Zhi ; 104(18): 1572-1577, 2024 May 14.
Artigo em Chinês | MEDLINE | ID: mdl-38742343

RESUMO

The incidence of differentiated thyroid cancer is increasing rapidly worldwide, with subcentimeter papillary thyroid carcinoma (SPTC) with a diameter of less than 1 cm accounting for more than 50%. Active surveillance (AS) as an alternative to immediate surgery for low-risk SPTC was launched in Japan in the 1990s and has been implemented in several countries, including Japan and the United States. However, the indications and safety of performing AS for low-risk SPTC remain controversial. In this article, the author summarizes the existing literature and explores its limitations of AS implementation, the effectiveness of surgical treatment, and the different attitudes of countries on AS, aiming to provide some references for the treatment options of low-risk SPTC.


Assuntos
Carcinoma Papilar , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Conduta Expectante , Carcinoma/cirurgia , Carcinoma/patologia
7.
BMC Med Res Methodol ; 24(1): 90, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637725

RESUMO

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is known for its high propensity for lymph node (LN) invasion. Inadequate LN dissection may compromise the precision of prognostic assessments. This study introduces a log odds of positive lymph nodes (LODDS) method to address this issue and develops a novel LODDS-based nomogram to provide accurate prognostic information. METHODS: The study analyzed data from 1,901 patients with breast IMPC from the Surveillance, Epidemiology, and End Results database. It assessed the relationships between LODDS and the number of excised LN (eLN), positive LN (pLN), and the pLN ratio (pLNR), identifying an optimal threshold value using a restricted cubic spline method. Predictive factors were identified by the Cox least absolute shrinkage and selection operator (Cox-LASSO) regression and validated through multivariate Cox regression to construct a nomogram. The model's accuracy, discrimination, and utility were assessed. The study also explored the consequences of excluding LODDS from the nomogram and compared its effectiveness with the tumor-node-metastasis (TNM) staging system. RESULTS: LODDS improved N status classification by identifying heterogeneity in patients with pLN ratios of 0% (pLN =0) or 100% (pLN =eLN) and setting -1.08 as the ideal cutoff. Five independent prognostic factors for breast cancer-specific survival (BCSS) were identified: tumor size, N status, LODDS, progesterone receptor status, and histological grade. The LODDS-based nomogram achieved a strong concordance index of 0.802 (95% CI: 0.741-0.863), surpassing both the version without LODDS and the conventional TNM staging in all tests. CONCLUSIONS: For breast IMPC, LODDS served as an independent prognostic factor, its effectiveness unaffected by the anatomical LN count, enhancing the accuracy of N staging. The LODDS-based nomogram showed promise in offering more personalized prognostic information.


Assuntos
Neoplasias da Mama , Carcinoma , Humanos , Feminino , Nomogramas , Prognóstico , Estadiamento de Neoplasias , Linfonodos/patologia , Carcinoma/patologia
8.
BMJ Case Rep ; 17(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569728

RESUMO

We report a young pregnant woman with large midline thoracic mass and markedly elevated serum alpha-fetoprotein (AFP) levels. Initially suspected as a germ cell tumour (GCT) due to age, site, and high AFP levels, a biopsy unveiled a high-grade malignant tumour characterised by undifferentiated monotonous cells. Although tumour cells exhibited positive AFP, the overall immunoprofile did not provide additional evidence to support GCT. Further work-up showed positive for NUT (nuclear protein in testis) immunostaining and the presence of BRD4-NUT1 fusion, confirming the diagnosis of NUT carcinoma. On radiology, there were extensive metastases to lungs, liver, vertebrae, and placenta. Despite aggressive chemotherapy, radiotherapy and immunotherapy, she did not respond to the therapies. Fortunately, her child was not affected by the carcinoma. This is the first case highlighting that thoracic lung primary NUT carcinoma can spread to the placenta and manifest with elevated serum AFP levels, potentially leading to misdiagnosis as GCT both clinically and pathologically.


Assuntos
Carcinoma , alfa-Fetoproteínas , Feminino , Humanos , Gravidez , alfa-Fetoproteínas/metabolismo , Proteínas que Contêm Bromodomínio , Carcinoma/patologia , Proteínas de Ciclo Celular , Proteínas Nucleares , Placenta/patologia , Fatores de Transcrição
9.
Zhonghua Bing Li Xue Za Zhi ; 53(4): 331-336, 2024 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-38556815

RESUMO

Objective: To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy. Methods: Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers. Results: All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors. Conclusions: The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.


Assuntos
Adenocarcinoma , Neoplasias da Mama , Carcinoma , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Carcinoma/patologia , Adenocarcinoma/patologia , Biópsia , Diagnóstico Diferencial , Proteínas Repressoras
11.
Iran J Med Sci ; 49(3): 156-166, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38584650

RESUMO

Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProExTMC, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics. Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProExTMC, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method. Results: The expression of VEGF, hTERT, and ProExTMC was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively). Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProExTMC is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC.


Assuntos
Carcinoma , Infecções por Papillomavirus , Neoplasias dos Seios Paranasais , Humanos , Fator A de Crescimento do Endotélio Vascular , Proteína X Associada a bcl-2 , Papillomavirus Humano , Prognóstico , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Papillomaviridae , Recidiva Local de Neoplasia/complicações , Carcinoma/diagnóstico , Carcinoma/patologia , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/patologia , Receptores ErbB , Recidiva , Biomarcadores
13.
Vet Comp Oncol ; 22(2): 295-302, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38659202

RESUMO

Canine urothelial carcinoma (UC) and prostate carcinoma (PC) frequently exhibit the BRAFV595E mutation, akin to the BRAFV600E mutation common in various human cancers. Since the initial discovery of the BRAF mutation in canine cancers in 2015, PCR has been the standard method for its detection in both liquid and tissue biopsies. Considering the similarity between the canine BRAFV595E and human BRAFV600E mutations, we hypothesized that immunohistochemistry (IHC) using a BRAFV600E-specific antibody could effectively identify the canine mutant BRAFV595E protein. We tested 122 canine UC (bladder n = 108, urethra n = 14), 21 PC, and benign tissue using IHC and performed digital droplet PCR (ddPCR) on all 122 UC and on 14 IHC positive PC cases. The results from ddPCR and IHC were concordant in 99% (135/136) of the tumours. Using IHC, BRAFV595E was detected in 72/122 (59%) UC and 14/21 (65%) PC. Staining of all benign bladder and prostate tissues was negative. If present, mutant BRAF staining was homogenous, with rare intratumour heterogeneity in three (4%) cases of UC. Additionally, the BRAFV595E mutation was more prevalent in tumours with urothelial morphology, and less common in glandular PC or UC with divergent differentiation. This study establishes that BRAFV600-specific IHC is a reliable and accurate method for detecting the mutant BRAFV595E protein in canine UC and PC. Moreover, the use of IHC, especially with tissue microarrays, provides a cost-efficient test for large-scale screening of canine cancers for the presence of BRAF mutations. This advancement paves the way for further research to define the prognostic and predictive role of this tumour marker in dogs and use IHC to stratify dogs for the treatment with BRAF inhibitors.


Assuntos
Doenças do Cão , Imuno-Histoquímica , Mutação , Neoplasias da Próstata , Proteínas Proto-Oncogênicas B-raf , Neoplasias da Bexiga Urinária , Cães , Animais , Doenças do Cão/genética , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Masculino , Neoplasias da Próstata/veterinária , Neoplasias da Próstata/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Imuno-Histoquímica/veterinária , Neoplasias da Bexiga Urinária/veterinária , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Feminino , Carcinoma/veterinária , Carcinoma/genética , Carcinoma/patologia , Carcinoma/metabolismo , Carcinoma/diagnóstico , Carcinoma de Células de Transição/veterinária , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia
14.
Eur J Endocrinol ; 190(5): 374-381, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38652802

RESUMO

BACKGROUND: Lymph node metastases in papillary thyroid cancer (PTC) increase the risk for persistent and recurrent disease. Data on the predictive value of histopathological features of lymph node metastases, however, are inconsistent. The aim of this study was to evaluate the prognostic significance of known and new histopathological features of lymph node metastases in a well-defined cohort of PTC patients with clinically evident lymph node metastases. METHODS: A total of 1042 lymph node metastases, derived from 129 PTC patients, were reexamined according to a predefined protocol and evaluated for diameter, extranodal extension, cystic changes, necrosis, calcifications, and the proportion of the lymph node taken up by tumor cells. Predictors for a failure to achieve a complete biochemical and structural response to treatment were determined. RESULTS: The presence of more than 5 lymph node metastases was the only independent predictor for a failure to achieve a complete response to treatment (odds ratio [OR] 3.39 [95% CI, 1.57-7.33], P < .05). Diameter nor any of the other evaluated lymph node features were significantly associated with the response to treatment. CONCLUSIONS: Detailed reexamination of lymph nodes revealed that only the presence of more than 5 lymph node metastases was an independent predictor of failure to achieve a complete response to treatment. No predictive value was found for other histopathological features, including the diameter of the lymph node metastases. These findings have the potential to improve risk stratification in patients with PTC and clinically evident lymph node metastases.


Assuntos
Carcinoma Papilar , Linfonodos , Metástase Linfática , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Metástase Linfática/patologia , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Adulto , Carcinoma Papilar/patologia , Idoso , Linfonodos/patologia , Prognóstico , Resultado do Tratamento , Valor Preditivo dos Testes , Adulto Jovem , Carcinoma/patologia , Carcinoma/secundário , Carcinoma/terapia , Estudos Retrospectivos , Estudos de Coortes
15.
Hum Pathol ; 146: 57-65, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38615998

RESUMO

Mucinous tubular and spindle cell carcinoma (MTSCC) shows significant overlap with papillary renal cell carcinoma (PRCC), and harbor recurrent copy-number alterations (CNA). We evaluated 16 RCC with features suggestive of MTSCC using chromosomal microarrays. The cohort was comprised of 8 females and males, each, with an age range of 33-79 years (median, 59), and a tumor size range of 3.4-15.5 cm (median, 5.0). Half the tumors were high-grade (8/16, 50%) with features such as necrosis, marked cytologic atypia, and sarcomatoid differentiation, and 5/16 (31%) were high stage (≥pT3a). Three (of 16, 19%) cases had a predominant (>95%) spindle cell component, whereas 5/16 (31%) were composed of a predominant (>95%) epithelial component. Most cases (12/16, 75%) exhibited a myxoid background and/or extravasated mucin, at least focally. Twelve (of 16, 75%) cases demonstrated CNA diagnostic of MTSCC (losses of chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22). In addition, 2 high-grade tumors showed loss of CDKN2A/B, and gain of 1q, respectively, both of which are associated with aggressive behavior. Three (of 16, 19%) cases, demonstrated nonspecific CNA, and did not meet diagnostic criteria for established RCC subtypes. One (of 16, 6%) low-grade epithelial predominant tumor (biopsy) demonstrated characteristic gains of 7, 17, and loss of Y, diagnostic of PRCC. MTSCC can be a morphologically heterogenous tumor. Our study validates the detection of characteristic chromosomal CNA for diagnostic use that may be useful in challenging cases with unusual spindle cell or epithelial predominant features, as well as in high-grade tumors.


Assuntos
Adenocarcinoma Mucinoso , Neoplasias Renais , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Adulto , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/diagnóstico , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/diagnóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Variações do Número de Cópias de DNA , Carcinoma/genética , Carcinoma/patologia , Carcinoma/diagnóstico , Análise de Sequência com Séries de Oligonucleotídeos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/diagnóstico , Valor Preditivo dos Testes , Gradação de Tumores , Reprodutibilidade dos Testes , Diagnóstico Diferencial
16.
Sci Rep ; 14(1): 9898, 2024 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688967

RESUMO

The clinical significance of the combination of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily.


Assuntos
Plaquetas , Linfócitos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Neutrófilos , Humanos , Masculino , Feminino , Neutrófilos/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/sangue , Linfócitos/patologia , Plaquetas/patologia , Adulto , Idoso , Curva ROC , Contagem de Plaquetas , Contagem de Linfócitos , Carcinoma/sangue , Carcinoma/mortalidade , Carcinoma/patologia , Adulto Jovem
17.
J Cutan Pathol ; 51(6): 424-429, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38481096

RESUMO

Nuclear protein in testis (NUT) carcinoma, molecularly defined by the NUTM1 gene rearrangement, is most commonly reported in young adults in the sinonasal tract, nasopharynx, or thorax. At these sites, NUT carcinoma is an extremely aggressive malignancy with dismal prognosis. Recently, five cases of primary cutaneous NUT adnexal carcinoma have been reported with BRD3 and NSD3 fusion partners. Although NUT adnexal carcinomas are shown to have metastatic potential, they may behave less aggressively than extracutaneous NUT carcinomas. We report a case of a 59-year-old man who underwent a biopsy of a 3-cm plantar mass, which showed BRD4::NUTM1 fusion. The tumor was a poorly differentiated dermal neoplasm showing cytologic atypia, large vesicular nuclei with prominent nucleoli, conspicuous mitotic activity, and foci of necrosis. Immunohistochemically, the tumor showed positivity for keratins, EMA, SOX10, and NUT, with patchy smooth muscle actin. Molecular testing revealed BRD4::NUTM1 rearrangement. With no alternative primary identified by imaging, a diagnosis of primary cutaneous NUT carcinoma was favored. We hope to contribute to the limited body of knowledge on this entity, with emphasis on recognition as well as studying and defining its prognostic differences from extracutaneous NUT carcinomas.


Assuntos
Proteínas Nucleares , Proteínas de Fusão Oncogênica , Neoplasias Cutâneas , Fatores de Transcrição , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Carcinoma/genética , Carcinoma/patologia , Carcinoma/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas que Contêm Bromodomínio
18.
Biomark Med ; 18(5): 169-179, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38440866

RESUMO

Objective: This study aimed to assess the value of PLK4 as a biomarker in papillary thyroid carcinoma (PTC). Methods: This study reviewed 230 PTC patients receiving surgical resections. PLK4 was detected in tumor tissues and samples of normal thyroid gland tissues by immunohistochemistry. Results: PLK4 was elevated in tumor tissues versus normal thyroid gland tissues (p < 0.001). Tumor PLK4 was linked with extrathyroidal invasion (p = 0.036), higher pathological tumor stage (p = 0.030), node stage (p = 0.045) and tumor/node/metastasis stage (p = 0.022) in PTC patients. Tumor PLK4 immunohistochemistry score >3 was linked with shortened disease-free survival (p = 0.026) and overall survival (p = 0.028) and independently predicted poorer disease-free survival (hazard ratio: 2.797; p = 0.040). Conclusion: Tumor PLK4 reflects extrathyroidal invasion, higher tumor stage and shortened survival in PTC.


Assuntos
Carcinoma Papilar , Carcinoma , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/cirurgia , Prognóstico , Proteínas Serina-Treonina Quinases/genética
19.
Radiother Oncol ; 194: 110189, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38432309

RESUMO

BACKGROUND AND PURPOSE: Whether concurrent chemoradiotherapy would provide survival benefits in patients with stage II and T3N0 NPC with adverse factors remains unclear in IMRT era. We aimed to assess the value of concurrent chemotherapy compared to IMRT alone in stage II and T3N0 NPC with adverse features. MATERIALS AND METHODS: 287 patients with stage II and T3N0 NPC with adverse factors were retrospectively analyzed, including 98 patients who received IMRT alone (IMRT alone group) and 189 patients who received cisplatin-based concurrent chemotherapy (CCRT group). The possible prognostic factors were balanced using propensity score matching (PSM). Kaplan-Meier analysis was used to evaluate the survival rates, and log-rank tests were employed to compare differences between groups. RESULTS: The median follow-up duration was 90.8 months (interquartile range = 75.6-114.7 months). The IMRT alone and the CCRT group were well matched; however, for all survival-related endpoints, there were no significant differences between them (5-year failure-free survival: 84.3% vs. 82.7%, P value = 0.68; 5-year overall survival: 87.3% vs. 90.6%, P value = 0.11; 5-year distant metastasis-free survival: 92.8% vs. 92.5%, P value = 0.97; 5-year locoregional relapse-free survival: 93.4% vs. 89.9%, P value = 0.30). The incidence of acute toxicities in the IMRT alone group was significantly lower than that in the CCRT group. CONCLUSION: For patients with stage II and T3N0 NPC with adverse features treated using IMRT, no improvement in survival was gained by adding concurrent chemotherapy; however, the occurrence of acute toxicities increased significantly. For those combined with non-single adverse factors, the comprehensive treatment strategy needs further exploration.


Assuntos
Quimiorradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Estadiamento de Neoplasias , Pontuação de Propensão , Radioterapia de Intensidade Modulada , Humanos , Masculino , Feminino , Quimiorradioterapia/efeitos adversos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Estudos Retrospectivos , Adulto , Radioterapia de Intensidade Modulada/efeitos adversos , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Estudos de Coortes , Taxa de Sobrevida , Carcinoma/terapia , Carcinoma/patologia , Carcinoma/mortalidade , Idoso
20.
PeerJ ; 12: e17077, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500523

RESUMO

Background: Metastatic disease resulting from mammary gland tumors (MGTs) is a known cause of death among dogs and cats. Keys to successful prevention and management strategies involve the accurate recording of diagnostic data. Methods: This retrospective study reviewed the epidemiology and classification of canine mammary gland tumors (CMTs) and feline mammary gland tumors (FMTs), as well as the factors including sex, age, and breed related to the occurrence of these tumors. Accordingly, 1,736 tumor biopsy cases were reported from 2012 to 2019 at Chiang Mai University Small Animal Hospital, Thailand, with 1,639 canine tumor biopsy cases and 97 feline tumor biopsy cases. Results: The proportion of CMTs was reported at 24.5% (401/1,639) for all canine tumor biopsy cases. Benign and malignant tumors were reported at 14.5% (58/401) and 85.5% (343/401) for all CMT cases, respectively. The mean age of dogs affected by benign CMTs was 9.0 ± 3.0 years, which was significantly lower than for malignant CMTs at 9.9 ± 2.8 years (P = 0.0239). According to histopathological classification, benign mixed tumors and simple carcinoma types were highest among benign and malignant CMT cases, respectively. Moreover, female dogs were at significantly higher risk of developing mammary gland tumors (OR = 45.8, 95% CI [3.9-86.0], P < 0.0001) than male dogs, as well as older dogs (>8 years) (OR = 1.7, 95% CI [1.2-2.2], P = 0.0001) compared to young ones (≤8 years). The proportion of FMTs was 37.1% (36/97) for all feline tumor biopsy cases. Benign and malignant tumors for all FMTs were reported at 16.7% (6/36) and 83.3% (30/36), respectively. According to histopathological classifications, adenoma and simple carcinoma were present in the highest proportion among benign and malignant FMTs, respectively. Female cats were at a significantly higher risk of developing mammary gland tumors than male cats (OR = 25.7, 95% CI [3.9-272.8], P < 0.0001). Conclusions and clinical importance: There was a high proportion of MGT cases compared with other tumor cases reported in a secondary care hospital in Chiang Mai, Thailand from 2012 to 2019, and malignant tumor biopsies have been more frequently observed than benign tumor biopsies in both CMT and FMT cases. The resulting data originating from this study can be an aid for veterinary oncologists in better educating clients and planning treatment and prevention strategies and it can be used as a basis for further experimental studies in the oncology section.


Assuntos
Carcinoma , Doenças do Gato , Doenças do Cão , Glândulas Mamárias Humanas , Neoplasias Mamárias Animais , Neoplasias das Glândulas Sudoríparas , Humanos , Gatos , Cães , Animais , Masculino , Feminino , Criança , Doenças do Gato/epidemiologia , Tailândia/epidemiologia , Estudos Retrospectivos , Glândulas Mamárias Humanas/patologia , Atenção Secundária à Saúde , Doenças do Cão/diagnóstico , Carcinoma/patologia , Biópsia/veterinária , Neoplasias Mamárias Animais/epidemiologia , Hospitais
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