Class III β-tubulin expression in advanced-stage serous ovarian carcinoma effusions is associated with poor survival and primary chemoresistance.
ABSTRACT The objective of this study was to analyze the clinical role of nestin, a stem cell marker, and class III β-tubulin in advanced-stage serous ovarian carcinoma. Nestin and class III β-tubulin protein expression were investigated in 217 effusions using immunohistochemistry. Results were analyzed for association with clinicopathologic parameters including chemotherapy response and survival. Class III β-tubulin and nestin were expressed in tumor cells in 98.6% and 95.6% of specimens, respectively. Staining extent was comparable in prechemotherapy and postchemotherapy effusions. No association was found with patient age, histologic grade, International Federation of Gynecology and Obstetrics stage, primary surgery versus secondary debulking, or residual disease volume. High class III β-tubulin expression in prechemotherapy effusions was significantly associated with primary chemoresistance (progression-free survival <6 months; P = .036) and with a trend for less favorable response to first-line treatment (P = .054). In univariate survival analysis, high class III β-tubulin expression in prechemotherapy effusions was significantly associated with poor overall survival (P = .021), with a trend for poor progression-free survival (P = .067). These associations did not have independent prognostic value in Cox multivariate analysis. Nestin expression was unrelated to chemoresistance or survival. Both class III β-tubulin and nestin are frequently expressed in serous ovarian carcinoma cells in effusions. Nestin does not provide predictive or prognostic data in this patient group, whereas class III β-tubulin expression in prechemotherapy effusions is associated with poor chemoresponse and shorter survival, suggesting that it may be a therapeutic target in ovarian cancer.
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ABSTRACT: The objective of this study was to investigate the expression and clinical role of the spindle checkpoint kinase budding uninhibited by benzimidazole 1 (Bub1) in primary and metastatic advanced-stage ovarian serous carcinoma. BUB1 mRNA expression was analyzed in 178 tumors (88 effusions, 38 primary carcinomas, and 52 solid metastases) from 144 patients with advanced-stage disease using quantitative real-time polymerase chain reaction (PCR). Bub1 protein expression by Western blotting was studied in 63 carcinomas (30 effusions and 33 solid lesions). BUB1 mRNA expression at different anatomic sites was studied for association with clinicopathologic parameters, including chemotherapy resistance and survival. BUB1 mRNA was universally expressed in serous carcinomas, irrespective of anatomic site. BUB1 mRNA levels were uniformly low in six ovarian surface epithelium specimens analyzed for comparative purposes. Bub1 protein was expressed in 22/30 effusions and 28/33 solid lesions. BUB1 mRNA expression was significantly higher in chemo-naïve primary carcinomas and solid metastases compared to specimens obtained following neoadjuvant chemotherapy (p < 0.001) and was unrelated to chemotherapy exposure in effusions nor to chemoresponse or survival at any anatomic site. BUB1 mRNA levels in both effusions and solid lesions were strongly related to the mRNA levels of AURKA and AURKB previously studied in this cohort (p < 0.001 for both). Bub1 is widely expressed in primary and metastatic OC, suggesting a biological role in this cancer. BUB1 mRNA levels are lower following chemotherapy exposure in solid lesions, though its presence is unrelated to clinical behavior including response to chemotherapy and survival. BUB1 is co-expressed with AURKA and AURKB suggesting biological relationship between these spindle cell components.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 04/2014; · 2.56 Impact Factor
- Expert Review of Obstetrics & Gynecology 01/2014; 6(4).
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ABSTRACT: This article reviews the main prognostic and predictive biomarkers of endometrial (EC) and ovarian carcinoma (OC). In EC, prognosis still relies on conventional pathological features such as histological type and grade, as well as myometrial or lymphovascular space invasion. Estrogen receptor, p53, Ki-67, and ploidy analysis are the most promising biomarkers among a long list of molecules that have been proposed. Also, a number of putative predictive biomarkers have been proposed in molecular targeted therapy. In OC, prognosis is predominantly dependent on disease stage at diagnosis and the extent of residual disease at primary operation. Diagnostic markers which aid in establishing histological type in OC are available. However, not a single universally accepted predictive or prognostic marker exists to date. Targeted therapy has been growingly focused at in recent years, in view of the frequent development of chemoresistance at recurrent disease. The present review emphasizes the crucial role of correct pathological classification and stringent selection criteria of the material studied as basis for any evaluation of biological markers. It further emphasizes the promise of targeted therapy in EC and OC, while simultaneously highlighting the difficulties remaining before this can become standard of care.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 02/2014; · 2.56 Impact Factor