Expression Patterns of Cytokeratins (CK7, CK20, CK19, CK AE1/AE3) in Atypical Endometrial Hyperplasia Coexisting with Endometrial Cancer
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ABSTRACT:
SUBMITTER: Vasilevska D
PROVIDER: S-EPMC11354644 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
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Project description:The incidence of oropharyngeal squamous cell carcinoma (OPSCC) mediated by human papilloma virus (HPV) has been steadily increasing worldwide. The specific pathogenesis of HPV-mediated head and neck squamous cell carcinoma (HNSCC) usually induces carcinogenesis in the oropharynx and the roles of CK7, CK19 and p16 in the carcinogenesis mechanism of HPV-mediated OPSCC still remain uncertain. We collected case data and paraffin samples of 69 cases of OPSCC and 40 cases of OSCC from July 2009 to December 2021. Immunohistochemistry was performed on serial paraffin sections from all cases to analyze the expression patterns of CK7, CK19, and p16. HPV-mediated (p16+) and non-HPV-mediated OPSCC were differentiated based on p16 expression. Three to six fields were selected from each case for observation of the expression intensity, localization, and interrelationship of the three proteins. In both cancerous nests and pericancerous normal epithelium of OPSCC, various expression combinations of CK7, CK19 and p16 were observed, including CK7+CK19+p16+, CK7-CK19+p16+, and CK7+CK19+p16-, while no expression of CK7+CK19-p16+ was found. The expression of CK7 with CK19, CK7 with p16, and CK19 with p16 all showed consistency in OPSCC (P < 0.05) while only the expression of CK7 and CK19 demonstrated consistency in OSCC (P < 0.05). The positive rates and H-scores for CK7/CK19 in HPV-mediated (p16+) OPSCC were significantly higher than those in non-HPV-mediated OPSCC and OSCC (P < 0.05). These results suggest that CK7, CK19 and p16 may relate to HPV-mediated OPSCC. The interaction of CK7, CK19 and p16 may affect the development of HPV-mediated OPSCC.
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Project description:Colorectal cancer remains one of the major cancer- related deaths despite progress in the treatment during past decades. Detection of disease at earlier stages reduces its mortality. The aim of current study was to investigate expression of Cytokeratin 19 (CK19), Cytokeratin 20 (CK20) and Guanylyl Cyclase C (GCC) mRNA in peripheral blood of non- metastatic colorectal cancer patients which may result into introducing of an early detection test. 25 patients with colorectal cancer and 25 healthy controls were recruited. Blood was obtained from all individuals. Expression of CK19 and CK20 and GCC mRNA and 18SrRNA (as reference gene) were determined based on real- time RT-PCR on total RNA from blood. CK19, CK20 and GCC expression had been detected in 68%, 76% & 52% of patient group, respectively, which was higher than healthy group, with 8%, 32% and 0% expression, respectively (p<0.05). CK20 was over-expressed 8- fold more in patients compared to controls. Similar result was found for CK19 with 4- fold over- expression. Sensitivity and specificity of combination of markers were 88% and 68%, respectively. Current data suggest that the detection of CK20 & CK19 as relative sensitive markers may become a valuable tool for primary diagnosis of colorectal cancer in early stages. GCC could be considered as a specific tumor marker for detection of colorectal cancer. Higher expression of these markers in patients may be considered as a relative good tool for the diagnosis of disease in non- metastatic stages.
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Project description:Using mouse models of endometrial tumorigenesis based on two of the most common molecular alterations found in primary human UEC we sought to characterize the transition from CAH to carcinoma to identify clinically useful biomarkers. In order to identify novel candidate genes associated with invasion, global gene expression profiles were compared from uteri with extensive CAH and carcinoma. Keywords: Gene expression profiling RNA was extracted from uterine segments with either CAH or invasive carcinoma from Pten+/-;Mlh1-/- , Pten+/-;Mlh1+/+ and Wild type female mice. The RNA was hybridized to Affymetrix mouse 430A chip in order to determine changes in global gene expression patterns
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Project description:Using mouse models of endometrial tumorigenesis based on two of the most common molecular alterations found in primary human UEC we sought to characterize the transition from CAH to carcinoma to identify clinically useful biomarkers. In order to identify novel candidate genes associated with invasion, global gene expression profiles were compared from uteri with extensive CAH and carcinoma. Keywords: Gene expression profiling
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Project description:ObjectiveAlthough a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia.MethodsA case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model.ResultsThe most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors.ConclusionsOlder age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients.
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