Objective There are known disparities in endometrial cancer survival with black women who experience a greater risk of death compared with white women. The purpose of this investigation was to ...evaluate the role of comorbid conditions as modifiers of endometrial cancer survival by race. Study Design Two hundred seventy-one black women and 356 white women who had been diagnosed with endometrial cancer from 1990-2005 were identified from a large urban integrated health center. A retrospective chart review was conducted to gather information on comorbid conditions and other known demographic and clinical predictors of survival. Results Black women experienced a higher hazard of death from any cause (hazard ratio HR 1.51; 95% confidence interval CI, 1.22–1.87) and from endometrial cancer (HR, 2.42; 95% CI, 1.63–3.60). After adjustment for known clinical prognostic factors and comorbid conditions, the hazard of death for black women was elevated but no longer statistically significant for overall survival (HR, 1.22; 95% CI, 0.94–1.57), and the hazard of death from endometrial cancer remained significantly increased (HR, 2.27; 95% CI, 1.39–3.68). Both black and white women with a history of hypertension experienced a lower hazard of death from endometrial cancer (HR, 0.47; 95% CI, 0.23–0.98; and HR, 0.35; 95% CI, 0.19–0.67, respectively). Conclusion The higher prevalence of comorbid conditions among black women does not explain fully the racial disparities that are seen in endometrial cancer survival. The association between hypertension and a lower hazard of death from endometrial cancer is intriguing, and further investigation into the underlying mechanism is needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective The objective of the study was to evaluate the prognosis of ovarian cancer arising in endometriosis. Study Design We retrospectively compared 42 cases of endometriosis-associated ovarian ...cancer (EAOC) with 184 cases of ovarian carcinoma without endometriosis (OC). Results The median age in the EAOC group was 52 vs 59 years in OC ( P < .05). In comparison with OC, the EAOC patients were more likely to have low-grade (21% vs 8%; P = .04) and early-stage tumors (International Federation of Gynecology and Obstetrics I and II combined) (49% vs 24%; P = .002). Clear cell (21% vs 2%) and endometrioid (14% vs 3%) tumors were more frequent in EAOC, whereas mucinous tumors were more prevalent in OC ( P = .001). The median survival (199 vs 62 months) and the 5 year survival (62% vs 51%) were better for EAOC when compared with OC ( P = .038). After controlling for age, stage, grade, and treatment, association with endometriosis was not an independent predictor of better survival in ovarian cancer. Conclusion As such, EAOC has a much better survival rate than OC. This could be explained by the higher prevalence of early-stage and low-grade tumors in EAOC when compared with OC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary The polycomb group protein, enhancer of zeste homolog 2, is a transcriptional repressor involved in cell cycle regulation and has been linked to aggressive breast cancer. We examined the ...clinical and biological significance of enhancer of zeste homolog 2 expression in triple-negative breast cancers. Tissue microarrays were constructed with invasive breast cancer cases and stained with the enhancer of zeste homolog 2, cytokeratin 5/6, epidermal growth factor receptor 1, and p53. The expression of these markers was correlated with clinicopathologic variables and patients' outcome. Furthermore, in vivo enhancer of zeste homolog 2 gene silencing was achieved using small interfering RNA incorporated into chitosan nanoparticles. Of 261 cases of invasive breast cancer, high expression of the enhancer of zeste homolog 2 was detected in 87 (33%) cases, and it was strongly associated with a triple-negative breast cancer phenotype ( P < .001) compared with all other non–triple-negative breast cancers. Furthermore, high enhancer of zeste homolog 2 was significantly associated with high histologic grade ( P = .01), estrogen receptor negativity ( P < .001), progesterone receptor negativity ( P < .001), epidermal growth factor receptor positivity ( P = .04), and high p53 expression ( P < .001). Survival analysis demonstrated that patients with high enhancer of zeste homolog 2 had a poorer overall survival compared with those with low enhancer of zeste homolog 2 ( P = .03), and it retained its significance as an independent prognostic factor ( P = .02). In addition, enhancer of zeste homolog 2 gene silencing resulted in a significant reduction in tumor growth ( P < .01) in the orthotopic MB-231 mouse model of breast carcinoma. Our results show that high enhancer of zeste homolog 2 expression is significantly associated with triple-negative breast cancer and decreased survival. Enhancer of zeste homolog 2 may represent a potential therapeutic target for this aggressive disease, which warrants further investigation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Prognosis of endometrial adenocarcinoma is favorable; however, the risk of recurrence ranges from 7% to 13%. Recurrence has been related to age, tumor type, International Federation of ...Gynecology and Obstetrics grade, depth of invasion, and lymphovascular invasion (LVI); however, morphologic features that would predict the site of recurrence have not been established. In this multi-institutional study, we reviewed 589 patients with International Federation of Gynecology and Obstetrics grades 1 or 2 endometrial adenocarcinoma, endometrioid type. Cox proportional hazard analysis was used to identify univariate and multivariate risk factors for recurrence and survival. Univariate analysis revealed features of tumors that recurred only in the vagina: low nuclear grade; superficial myoinvasion; minimal to no LVI; and minimal myoinvasion with microcystic, elongated, and fragmented (MELF) pattern; low nuclear grade and superficial myoinvasion persisted on multivariate analysis. Features of tumors that recurred at other sites included large size, deep myoinvasion, tumor necrosis, 1 or more LVI foci, LVI foci distant/deeper than invasive tumor front, MELF myoinvasion pattern, lower uterine segment and cervical stromal involvement, pelvic and/or paraaortic lymph node metastases at presentation, and higher grade of tumor in the metastatic foci, whereas increased percentage of solid component and lower percentage of mucinous features were marginally associated. Tumors with recurrences only in vagina had different features than tumors that recurred at other sites. The presence of tumor necrosis, MELF foci at the invasive tumor front, and the percentage of solid component and mucinous features could be helpful in grading endometrioid adenocarcinomas, if a 2-tier rather than a 3-tier grading system is accepted in the future.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Clear cell carcinoma originating in the abdominal wall is rare and usually develops within endometriotic implants in the scar. We describe 2 patients: a 42 year old with a 15 cm mass on the abdominal ...wall treated with neoadjuvant chemotherapy and excision and a 51 year old with a 6 cm abdominal mass treated with excision and adjuvant radiotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Fibroepithelial lesions (FEL) of the breast are notoriously difficult to classify on core needle biopsies. The goal of this study was to evaluate interobserver variability and accuracy of ...subclassifying difficult FELs into fibroadenoma (FA) and phyllodes tumors (PTs). We identified 50 breast core needle biopsies, initially diagnosed generically as FEL, with subsequent excision and final diagnosis of either FA or benign PT. Five surgical pathologists from one institution independently reviewed these in 3 rounds. The pathologists were blinded to the final excisional diagnosis. Two diagnostic categories were allowed: FA and PT. A set of histologic criteria was provided including the presence of subepithelial condensation, stromal heterogeneity, overgrowth, pleomorphism, fragmentation, cellularity, adipose tissue entrapment, and mitotic count and asked to review the slides for the second round. A third round of interpretations was conducted after each criterion was defined. Interobserver agreement for the diagnosis and each criterion was evaluated using the κ level of agreement. Accuracy of ratings to final diagnosis was calculated using Wilcoxon signed-rank test. κ Values for interobserver agreement were fair for the first and second rounds varying from 0.20 to 0.22, respectively. This increased to 0.27 in round 3. When considering each category, the κ value varied from 0.26 to 0.29 for FA and 0.28 to 0.14 for PT. Overall, there was fair agreement between the pathologists in all categories. The rate of correctly diagnosed cases ranged from 40% in the first round, to 48% in the second round, to 67% in round 3. Overall the pathologists performed better in identifying FA than PT. The accuracy of interpretations was significantly different between the first (40%), second (48%), and third rounds (67%).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Purpose Poorer survival from head and neck squamous cell carcinoma (HNSCC) in African Americans (AA) may be due to disparity in the prevalence of Human Papillomavirus (HPV) but earlier ...studies often failed to control other etiological factors. We aimed to elucidate whether racial disparities in HPV prevalence and overall survival were due to confounding from smoking or alcohol use. Materials and methods 385 patients with SCC of the mouth, pharynx, nose, or larynx who had surgical resection at Wayne State University affiliated hospitals were identified through a population-based cancer registry. Formalin fixed paraffin embedded tissue blocks were used to determine the presence of HPV DNA and its genotype using a sensitive broad-spectrum PCR technique. Patients’ demographics, tumor characteristics and vital status were obtained through record linkage with the registry data and smoking and alcohol information was abstracted from medical record. Cox’s proportional hazard model and unconditional logistic regression models were employed to analyze the overall survival and tumor HPV-positivity, respectively. Results HPV positivity in oropharyngeal cancer was substantially lower in AA than in other racial groups (odds ratio 0.14, 95% confidence interval (CI) 0.05–0.37) and adjustment for smoking or alcohol did not change this association. However, a significantly increased hazard ratio of death in AA oropharyngeal cancer patients (univariable hazard ratio (HR) 2.55, 95% CI 1.42–4.59) decreased to almost unity (HR 1.49, 95% CI 0.75–2.93) after adjustment for HPV and smoking. Conclusions Lower HPV prevalence in AA largely accounts for their poorer survival from oropharyngeal cancer, but not other HNSSC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose To investigate the possibility of inhibiting the progression of pancreatic ductal adenocarcinoma (PDAC) by facilitating the expression of E-cadherin through the enforced expression of ...microRNA-101 (miR-101). Methods In situ hybridization was conducted with archival tissue using a double digoxigenin-labeled probe. Chromatin immunoprecipitation (ChIP) assay was conducted with EZ-Magna ChIPTM A. Gene profile analysis, Western blot, and immunoprecipitation assays were performed using standard protocols. Results We found that decreased miR-101 expression observed in archival patient tissues was significantly associated with poor prognosis indicated by low-intensity staining in high-grade tumors. ChIP assays using anti-enhancer of zeste homolog 2 (EZH2) antibodies indicated not only the interaction of EZH2 to the CDH1 (E-cadherin) promoter, but also that this interaction was significantly diminished in cells transfected with pre–miR-101. We observed a global downregulation of trimethylated lysine 27 of H3 histone (H3K27me3) along with upregulation of the enzymes histone deacetylase -1 and -2 with the re-expression of miR-101. Further, we observed lesser levels of transcriptional factors that inhibit the CDH1 promoter with pre–miR-101 treatment. Western blot analysis confirmed the enhanced E-cadherin expression. PANC-1 cells transduced with pre–miR-101 displayed markedly attenuated growth in SCID mice. Conclusion These results suggest the potential therapeutic use of miR-101–enforced expression for inhibition of PDAC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective The purpose of this study was to determine whether cervical shortening of a ripe cervix at term is associated with changes in the cervical transcriptome. Study Design Sonographically ...measured cervical lengths and biopsy specimens were obtained from 19 women at term who were not in labor with a ripe cervix. Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix Inc, Santa Clara, CA) were used. Gene expression was analyzed as a function of cervical length. Gene Ontology, pathway analyses, quantitative real-time reverse transcription–polymerase chain reaction, and immunohistochemistry were performed. Results Cervical length shortening was associated with differential expression of 687 genes. Fifty-four biologic processes, 22 molecular functions, and 9 pathways were enriched. Quantitative real-time reverse transcription–polymerase chain reaction analysis confirmed differential expression of 13 genes. Bone morphogenetic protein-7, claudin-1, integrin beta-6, and endometrial progesterone–induced protein messenger RNA, and protein expressions were down-regulated with cervical shortening. Conclusion Sonographic cervical shortening in patients at term who are not in labor with a ripe cervix is associated with changes in the uterine cervix transcriptome. The epithelial-mesenchymal transition may participate in the mechanism of cervical shortening at term.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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