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Aldehyde dehydrogenase 1/epidermal growth factor receptor coexpression is characteristic of a highly aggressive, poor-prognosis subgroup of high-grade serous ovarian carcinoma


Liebscher, Catarina Alisa; Prinzler, Judith; Sinn, Bruno Valentin; Budczies, Jan; Denkert, Carsten; Noske, Aurelia; Sehouli, Jalid; Braicu, Elena Ioana; Dietel, Manfred; Darb-Esfahani, Silvia (2013). Aldehyde dehydrogenase 1/epidermal growth factor receptor coexpression is characteristic of a highly aggressive, poor-prognosis subgroup of high-grade serous ovarian carcinoma. Human Pathology, 44(8):1465-1471.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2013
Deposited On:11 Sep 2013 07:29
Last Modified:05 Apr 2016 16:58
Publisher:Elsevier
ISSN:0046-8177
Publisher DOI:https://doi.org/10.1016/j.humpath.2012.12.016
PubMed ID:23465277

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