Hetland TE, Hellesylt E, Flørenes VA, Tropé C, Davidson B, Kærn JClass III β-tubulin expression in advanced-stage serous ovarian carcinoma effusions is associated with poor survival and primary chemoresistance. Hum Pathol 42(7): 1019-1026
Department of Gynecologic Oncology, Oslo University Hospital, Norwegian Radium Hospital, N-0424 Oslo, Norway. Human pathology
(Impact Factor: 2.77).
02/2011; 42(7):1019-26. DOI: 10.1016/j.humpath.2010.10.025
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.
Available from: Nathaniel Melling
- "Class III β-tubulin (TUBB3) is a microtubule protein, normally expressed in cells of neuronal origin and involved in crucial cellular roles including maintenance of cell shape, intracellular transport, meiosis and mitosis (reviewed in ). Expression of TUBB3 has also been described in several extraneuronal cells such as melanocytes, spermatozoa, follicular lymphoid cells and neuroendocrine cells of the fetal respiratory epithelium (reviewed in ) and was found overexpressed in several solid tumors, including non-small-cell lung cancer , ovarian cancer  , urothelial carcinoma of the bladder , prostate cancer  and head and neck squamous cell carcinoma . High levels of βIII-tubulin expression were also described to be associated with poor clinical outcome in various cancers including non-small-cell lung cancer, ovarian cancer, urothelial carcinoma of the bladder    and prostate cancer   . "
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ABSTRACT: Introduction/Background: βIII-tubulin expression correlates with poor outcome in various malignancies. Materials and methods: βIII-tubulin expression was analyzed by immunohistochemistry on a tissue microarray containing 1800 colorectal cancers. Results were compared to clinic-pathological and molecular parameters. Results: βIII-tubulin expression was detectable in 79.2% of 1619 interpretable colorectal cancers. Whole tumor slide analysis showed that βIII-tubulin is homogenously expressed in CRC. High βIII-tubulin expression was associated with left-sided tumor localization (p=0.0303) and nuclear β-catenin expression (p=0.003). High βIII-tubulin expression was not linked to the gender of the patient (p=0.5842).When all tumors were analyzed the prognostic role of βIII-tubulin expression was not independent of pT stage, pN stage, tumor grade or tumor localization (p=0.0517). Conclusion: βIII-tubulin expression is not an independent prognostic parameter in colorectal cancer. The significant association with left-sided tumor localization and a key genomic alteration of colorectal cancer such as β-catenin suggest interaction with important pathways involved in colorectal cancer.
Available from: europepmc.org
- "Mutations in p53 are a common event in tumourigenesis, being particularly common in serous ovarian carcinomas (∼96% Hetland et al, 2011), but are remarkably uncommon in OCCC (9–10% Tan and Kaye, 2007). This implies that other antiapoptotic mechanisms are likely to be involved in the development of OCCC. "
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ABSTRACT: Ovarian clear cell carcinomas (OCCCs) account for about 5-13% of all epithelial ovarian carcinomas in Western populations. It is characterised by resistance to conventional platinum-based chemotherapy, and new therapeutic strategies are urgently required. This article will focus on how recent discoveries have enhanced our understanding of the molecular pathogenesis of OCCCs, leading to new therapeutic opportunities. These include mutations in ARID1A, which provides a link to endometriosis, upregulation of the phosphatidylinositol 3-kinase/AKT pathway, particularly through mutations of PIK3CA and inactivation of PTEN, and increased activity of pathways involved in angiogenesis. Targeting HER2, apoptotic escape mechanisms and mismatch repair defects offer additional opportunities for treating this enigmatic tumour subtype.British Journal of Cancer advance online publication, 4 April 2013; doi:10.1038/bjc.2013.126 www.bjcancer.com.
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ABSTRACT: Microtubules are highly dynamic structures that comprise a- and b-tubulin heterodimers which are essential in mitosis. These features make microtubules an important target for many natural and synthetic anticancer drugs. Mutations in b-tubulin that affect microtubule polymer levels or drug binding are associated with resistance to tubulin-binding agents such as paclitaxel. Moreover, aberrant expression of specific b-tubulin isotypes, namely bIII-tubulin as well as microtubule-binding proteins are now recognized as clinically important determinants in tumor aggressiveness and resistance to chemotherapy. More recently, it has been suggested that b-tubulins may also be linked to the tumorigenic phenotype of certain cancers such as non-small-cell lung cancer. Understanding the mechanisms whereby b-tubulins exert their effect on drug resistance and tumorigenesis are critical to the identification of novel drug targets and improvements in current therapies to increase the long-term survival of cancer patients. © 2012 Springer Science+Business Media, LLC. All rights reserved.
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