@article{d628ab9f6b90465486566627003da1b7,
title = "Aldehyde dehydrogenase 1/epidermal growth factor receptor coexpression is characteristic of a highly aggressive, poor-prognosis subgroup of high-grade serous ovarian carcinoma",
abstract = "In models of triple-negative breast cancer (TNBC), it has recently been shown that the epidermal growth factor receptor (EGFR) pathway is up-regulated in the aldehyde dehydrogenase 1 (ALDH1)-positive cancer stem cell fraction. Because high-grade serous ovarian carcinoma (HGSC) reveals strong molecular similarities to TNBC, we aimed to investigate the potential link between ALDH1 and EGFR in this entity. Expression of ALDH1 was investigated in 131 primary HGSCs using immunohistochemistry. Expression data were correlated with EGFR expression as well as with clinicopathologic parameters and survival. Forty-two carcinomas (32.1%) were positive for ALDH1 protein expression. Data on EGFR expression were available for 112 tumors. In these cases ALDH1 was significantly linked to EGFR expression (P <.0001). ALDH1 positivity was a significant negative prognostic factor for overall survival both in univariate (P =.010) and in multivariate survival analyses (P =.041). Tumors that were positive for both ALDH1 and EGFR had an exceptionally bad prognosis as compared with carcinomas with 1 or both markers negative in univariate analysis (P <.0001) and in the multivariate setting (P =.004). Our study suggests that similar to TNBC, there is a link between ALDH1 and EGFR expression in HGSC. Double positivity for both markers identifies a subgroup of highly aggressive, poor-prognosis cancers for which alternative treatment options - potentially EGFR-targeting drugs - should be evaluated.",
keywords = "ALDH1, EGFR, High-grade serous carcinoma, Ovarian, Prognosis",
author = "Liebscher, {Catarina Alisa} and Judith Prinzler and Sinn, {Bruno Valentin} and Jan Budczies and Carsten Denkert and Aurelia Noske and Jalid Sehouli and Braicu, {Elena Ioana} and Manfred Dietel and Silvia Darb-Esfahani",
note = "Funding Information: Limitations of our study are the retrospective character of our investigation and the rather small sample size. Therefore, a validation of our results in an independent study cohort should take place. The translational research project Ovarian Cancer Therapy–Innovative Models Prolong Survival, which is funded by the European Commission seventh framework program (project no. 279113) and in which our group is strongly involved, aims at identifying molecular characteristics of recurrent high-grade serous ovarian cancer and developing new therapeutic strategies in innovative model systems. The study is based on the hypothesis that the primary tumor includes a small population of resistant cells that are ultimately responsible for relapse and that by targeting this population front line we may prolong disease-free survival or even achieve cure ( http://www.octips.eu/ ). Because, on the basis of our present data, we think that ALDH1/EGFR expression analysis might help to identify this population of resistant cells (which could potentially constitute CSCs), we plan to validate our results in the Ovarian Cancer Therapy–Innovative Models Prolong Survival cohort, for which among other data on BRCA1/2 mutational status will be available. ",
year = "2013",
month = aug,
doi = "10.1016/j.humpath.2012.12.016",
language = "English",
volume = "44",
pages = "1465--1471",
journal = "Human Pathology",
issn = "0046-8177",
publisher = "W.B. Saunders",
number = "8",
}
