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

Felix AS, Sherman ME, Hewitt SM, Gunja MZ, Yang HP, Cora RL, Boudreau V, Ylaya K, Lissowska J, Brinton LA, Wentzensen N - Front Oncol (2015)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA ; Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA.

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.

No MeSH data available.


Related in: MedlinePlus

Heat map of cell-cycle marker distributions in histologic subtypes of ovarian and endometrioid endometrial cancer patients. Abbreviations: HGS, high-grade serous; LGS, low-grade serous; ME, mixed epithelial; MUC, mucinous; EO, endometrioid ovarian cancer; CC, clear cell; EM EC, endometrioid endometrial cancer.
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Figure 2: Heat map of cell-cycle marker distributions in histologic subtypes of ovarian and endometrioid endometrial cancer patients. Abbreviations: HGS, high-grade serous; LGS, low-grade serous; ME, mixed epithelial; MUC, mucinous; EO, endometrioid ovarian cancer; CC, clear cell; EM EC, endometrioid endometrial cancer.

Mentions: The distribution of cell-cycle and ki67 expression in histologic subtypes of ovarian cancer (low and high-grade serous, mixed epithelial, mucinous, endometrioid, and clear cell) and in endometrioid endometrial cancer patients is shown in Figure 2. Cells of light yellow indicate negative or low expression while dark orange cells indicate positive or high expression of the biomarker. Women with non-serous ovarian histology (mucinous, endometrioid, and clear cell tumors) had similar cell-cycle protein expression patterns: expression of p16, p27, and ki67 were negative while p21 expression was positive among these three subgroups. Serous ovarian cancers had a unique expression pattern dependent on grade: high-grade serous tumors were characterized by negative p21 expression while some low-grade serous tumors showed positive p21 expression. The mixed epithelial tumors had expression patterns intermediate to the serous and other non-serous subtypes, with positive p16 expression and negative expression of the other markers. Cell-cycle expression patterns among the endometrioid endometrial cancers showed intermediate expression of p16 and relatively low expression of the other markers.


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

Felix AS, Sherman ME, Hewitt SM, Gunja MZ, Yang HP, Cora RL, Boudreau V, Ylaya K, Lissowska J, Brinton LA, Wentzensen N - Front Oncol (2015)

Heat map of cell-cycle marker distributions in histologic subtypes of ovarian and endometrioid endometrial cancer patients. Abbreviations: HGS, high-grade serous; LGS, low-grade serous; ME, mixed epithelial; MUC, mucinous; EO, endometrioid ovarian cancer; CC, clear cell; EM EC, endometrioid endometrial cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321403&req=5

Figure 2: Heat map of cell-cycle marker distributions in histologic subtypes of ovarian and endometrioid endometrial cancer patients. Abbreviations: HGS, high-grade serous; LGS, low-grade serous; ME, mixed epithelial; MUC, mucinous; EO, endometrioid ovarian cancer; CC, clear cell; EM EC, endometrioid endometrial cancer.
Mentions: The distribution of cell-cycle and ki67 expression in histologic subtypes of ovarian cancer (low and high-grade serous, mixed epithelial, mucinous, endometrioid, and clear cell) and in endometrioid endometrial cancer patients is shown in Figure 2. Cells of light yellow indicate negative or low expression while dark orange cells indicate positive or high expression of the biomarker. Women with non-serous ovarian histology (mucinous, endometrioid, and clear cell tumors) had similar cell-cycle protein expression patterns: expression of p16, p27, and ki67 were negative while p21 expression was positive among these three subgroups. Serous ovarian cancers had a unique expression pattern dependent on grade: high-grade serous tumors were characterized by negative p21 expression while some low-grade serous tumors showed positive p21 expression. The mixed epithelial tumors had expression patterns intermediate to the serous and other non-serous subtypes, with positive p16 expression and negative expression of the other markers. Cell-cycle expression patterns among the endometrioid endometrial cancers showed intermediate expression of p16 and relatively low expression of the other markers.

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA ; Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA.

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.

No MeSH data available.


Related in: MedlinePlus