The molecular signature of endometriosis-associated endometrioid ovarian cancer differs significantly from endometriosis-independent endometrioid ovarian cancer

Abstract

Objective To determine whether endometriosis-associated endometrioid cancer (EAOC) is a specific entity compared with endometrioid cancer not associated with endometriosis (OC). Design Case-control study. Setting University hospital research laboratory. Patient(s) Seven patients with endometriosis-associated ovarian cancer EAOC and five patients each with OC, ovarian endometriosis, and benign ovaries. Intervention(s) Ovarian tissue samples were collected from surgical procedures. Main Outcome Measure(s) We hybridized cRNA samples to the Affymetrix HG-U133A microarray chip. Representative genes were validated by real time polymerase chain reaction. Result(s) We identified two main groups of genes: The first group contained the genes SICA2, CCL14, and TDGF1. These genes were equally regulated in endometriosis and EAOC but not in OC and benign ovaries. The second group contained the genes StAR, SPINT1, Keratin 8, FoxM1B, FOLR1, CRABP1, and Claudin 7. They were equally regulated in EAOC and OC but not in ovarian endometriosis and benign ovaries. Conclusion(s) That the first group is composed of the cytokines SICA2 and CCL14 and the growth factor TDGF1 indicates that the regulation of the autoimmune system and of inflammatory cytokines may be very important in the etiology of endometriosis and EAOC. That the second group is composed of genes that play a central role in cell-cell interaction, differentiation, and cell proliferation indicates that they may be important in the development of ovarian cancer in women with endometriosis.

Ovarian Cancer Development and Metastasis

“…25 Also, endometriotic lesions and endometroid ovarian carcinoma share overexpression of a distinct set of genes (eg, SICA2, CCL14, and Cripto-1) that are not deregulated in serous carcinomas. 26 The mutational data gathered in human cancer tissue from patients with endometrioid ovarian carcinomas were confirmed in a genetic mouse model of ovarian carcinoma. Expression of oncogenic KRAS or deletion of phosphatase and tensin homolog (PTEN) gave rise to endometriosis in the mouse ovary.…”

KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: association with concurrent endometriosis

“…For example, in a study comparing ovarian and uterine endometrioid adenocarcinomas, Catasus et al [8] noted that although the ovarian tumors overall had lower frequencies of PTEN mutations and microsatellite instability, these abnormalities were more common in the ovarian tumors associated with endometriosis. Recently, Banz et al [22] reported differences in gene profiling between endometriosis-associated and endometriosis-independent EC. Previously, we showed that although only a minority of low-grade EC expressed the Wilms tumor antigen WT1, none of the positive cases were related to endometriosis [23].…”

Unraveling endometriosis-associated ovarian carcinomas using integrative proteomics

“…For CC, a 113-gene signature that was reported to be able to differentiate between CC and high-grade serous OvCa was used ( Hughes et al , 2016) while for EC, two studies comparing EC against high-grade serous OvCa were used after identifying 15 underexpressed genes and 40 overexpressed genes in EC ( Banz et al , 2010; Uehara et al , 2015). Of the 113 CC-specific genes, 11/34 of the underexpressed genes were downregulated at the proteomic level while 40/79 overexpressed genes were upregulated at the proteomic level ( Figure 4A).…”