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; BRCA1; CI; CSC; EGFR; FFPE; FIGO; H&E; HGSC; HR; High-grade serous carcinoma; IRS; International Federation of Gynaecology and Obstetrics; MEC; OCTIPS; OS; Ovarian; Ovarian Cancer Therapy Innovative Models Prolong Survival; Prognosis; TMA; TNBC; aldehyde dehydrogenase 1; breast cancer antigen 1; cancer stem cell; confidence interval; epidermal growth factor receptor; formalin-fixed, paraffin-embedded; hazard ratio; hematoxylin and eosin; high-grade serous carcinoma; immunoreactivity score; mammary epithelial cells; overall survival; tissue microarray; triple-negative breast cancer.