Dataset Information

Cell-cycle protein expression in a population-based study of ovarian and endometrial cancers.

ABSTRACT: Aberrant expression of cyclin-dependent kinase (CDK) inhibitors is implicated in the carcinogenesis of many cancers, including ovarian and endometrial cancers. We examined associations between CDK inhibitor expression, cancer risk factors, tumor characteristics, and survival outcomes among ovarian and endometrial cancer patients enrolled in a population-based case-control study. Expression (negative vs. positive) of three CDK inhibitors (p16, p21, and p27) and ki67 was examined with immunohistochemical staining of tissue microarrays. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between biomarkers, risk factors, and tumor characteristics. Survival outcomes were only available for ovarian cancer patients and examined using Kaplan-Meier plots and Cox proportional hazards regression. Among ovarian cancer patients (n?=?175), positive p21 expression was associated with endometrioid tumors (OR?=?12.22, 95% CI?=?1.45-102.78) and higher overall survival (log-rank p?=?0.002). In Cox models adjusted for stage, grade, and histology, the association between p21 expression and overall survival was borderline significant (hazard ratio?=?0.65, 95% CI?=?0.42-1.05). Among endometrial cancer patients (n?=?289), positive p21 expression was inversely associated with age (OR???65?years of age?=?0.25, 95% CI?=?0.07-0.84) and current smoking status (OR: 0.33, 95% CI 0.15, 0.72) compared to negative expression. Our study showed heterogeneity in expression of cell-cycle proteins associated with risk factors and tumor characteristics of gynecologic cancers. Future studies to assess these markers of etiological classification and behavior may be warranted.

SUBMITTER: Felix AS

PROVIDER: S-EPMC4321403 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Cell-cycle protein expression in a population-based study of ovarian and endometrial cancers.

Felix Ashley S AS Sherman Mark E ME Hewitt Stephen M SM Gunja Munira Z MZ Yang Hannah P HP Cora Renata L RL Boudreau Vicky V Ylaya Kris K Lissowska Jolanta J Brinton Louise A LA Wentzensen Nicolas N

Frontiers in oncology 20150209

Aberrant expression of cyclin-dependent kinase (CDK) inhibitors is implicated in the carcinogenesis of many cancers, including ovarian and endometrial cancers. We examined associations between CDK inhibitor expression, cancer risk factors, tumor characteristics, and survival outcomes among ovarian and endometrial cancer patients enrolled in a population-based case-control study. Expression (negative vs. positive) of three CDK inhibitors (p16, p21, and p27) and ki67 was examined with immunohistoc ...[more]

PMID: 25709969

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Project description:ObjectiveBoth adenomyosis and endometriosis are characterized by the presence of ectopic endometrial glands and stroma and have been suggested to share some characteristics with malignant tumors. Although accumulating evidence indicates that endometriosis is associated with some cancer types, the cancer risks in patients with adenomyosis have been rarely examined. In this study, we investigated the relationship between adenomyosis and risks of common cancers.MethodsThis study included a cohort of 12,447 women with adenomyosis but not endometriosis, born in 1951-1984, and a cohort of 124,470 adenomyosis-free women matched by birth year. Their medical records (collected between 1996 and 2011) were obtained from the National Health Insurance Research Database of Taiwan. We first compared the distribution of cancer-free survival (CFS) between cohorts with and without adenomyosis. Subsequently, within the adenomyosis cohort, we examined whether time-to-onset of the identified cancer type was correlated with time-to-onset of adenomyosis. The Cox proportional hazards model was used to compare the distribution of CFS between the adenomyosis and adenomyosis-free cohorts and between the early- and late-diagnosed adenomyosis groups. For comparison, we further evaluated the cancer risks for a cohort of 10,962 women with endometriosis but not adenomyosis and a birth-year matched cohort of 109,620 endometriosis-free women.ResultsCompared with adenomyosis-free women, patients with adenomyosis had higher risks of endometrial and thyroid cancers, with estimated hazard ratios (HRs) (95% confidence interval) of 2.19 (1.51-3.16) and 1.70 (1.29-2.24), respectively. For both cancers, distributions of CFS were not significantly different between the early- and late-diagnosed adenomyosis groups. Furthermore, compared with endometriosis-free women, patients with endometriosis had higher risks of endometrial and ovarian cancers, with HRs of 1.89 (1.07-3.35) and 2.01 (1.27-3.16), respectively.ConclusionsWomen with adenomyosis are at higher risks of endometrial and thyroid cancers, while women with endometriosis are at higher risks of endometrial and ovarian cancers.

Project description:Despite improved outcomes in the past 30 years, less than half of all women diagnosed with epithelial ovarian cancer live five years beyond their diagnosis. Although typically treated as a single disease, epithelial ovarian cancer includes several distinct histological subtypes, such as papillary serous and endometrioid carcinomas. To address whether the morphological differences seen in these carcinomas represent distinct characteristics at the molecular level we analyzed DNA methylation patterns in 11 papillary serous tumors, 9 endometrioid ovarian tumors, 4 normal fallopian tube samples and 6 normal endometrial tissues, plus 8 normal fallopian tube and 4 serous samples from TCGA. For comparison within the endometrioid subtype we added 6 primary uterine endometrioid tumors and 5 endometrioid metastases from uterus to ovary. Data was obtained from 27,578 CpG dinucleotides occurring in or near promoter regions of 14,495 genes. We identified 36 locations with significant increases or decreases in methylation in comparisons of serous tumors and normal fallopian tube samples. Moreover, unsupervised clustering techniques applied to all samples showed three major profiles comprising mostly normal samples, serous tumors, and endometrioid tumors including ovarian, uterine and metastatic origins. The clustering analysis identified 60 differentially methylated sites between the serous group and the normal group. An unrelated set of 25 serous tumors validated the reproducibility of the methylation patterns. In contrast, >1,000 genes were differentially methylated between endometrioid tumors and normal samples. This finding is consistent with a generalized regulatory disruption caused by a methylator phenotype. Through DNA methylation analyses we have identified genes with known roles in ovarian carcinoma etiology, whereas pathway analyses provided biological insight to the role of novel genes. Our finding of differences between serous and endometrioid ovarian tumors indicates that intervention strategies could be developed to specifically address subtypes of epithelial ovarian cancer.

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Cell-cycle protein expression in a population-based study of ovarian and endometrial cancers.

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Cell-cycle protein expression in a population-based study of ovarian and endometrial cancers.

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