Abstract 4838: Inhibitor of differentiation-1 (Id1) expression correlates with epithelial-mesenchymal transition (EMT)-related proteins in epithelial ovarian cancer (EOC) and constitutes a novel prognostic factor
Authors: Heredia Victoria , Redondo Andres , Barriuso Jorge , Berjón Alberto , Perna Cristian , Cruz Patricia , Hernández Alicia , de Santiago Javier , Díaz Esther , Miguel María , Castelo Beatriz , Yébenes Laura , Feliú Jaime , Hardisson David , Mendiola Marta 
Published: August 2015

Aim

The first aim of this work was to investigate the expression of inhibitors of differentiation (ID) proteins in advanced Epithelial Ovarian Cancer (EOC) and its relation with Epithelial to Mesenchymal (EMT)-related markers. Secondly, we also studied their relation with patient clinical and pathological characteristics in order to establish their role as prognostic factors.

Methods

ID proteins expression was analyzed in 59 samples from EOC patients. We performed inmunohistochemistry (IHC) on tissue microarray sections with specific antibodies for ID1, ID2, ID3 and ID4. Immunoreactivity was H-scored for intensity (range 0 to 3) multiplied by percentage of positive cells. It has been previously described that ID genes are involved in EMT, so we correlated IDs with EMT- regulators, including ECAD, ZEB1, ZEB2, SNAIL, SLUG, LOX and LOXL2. We also explored their relation with clinical variables in our cohort.

Results

ID2 and ID3 proteins are uniformly expressed in our EOC series. ID1 and ID2 are also overexpressed in different proportions (41% and 88% of cases respectively). No correlation between increased ID proteins expression and histological subtype, tumor grading, debulking surgery status or treatment response was detected. We have found that ID1 overexpression correlates with prognosis, for Overall Survival (OS), HR: 1.05 (95% CI: 1.02 - 1.07) in the univariate analysis and for Time to Treatment Failure (TTF) in both, uni- and multivariate analysis adjusted to clinical factors (HR: 1.06; 95%CI: 1.02 - 1.1). This finding was confirmed when specifically analyzing the worst prognosis group of patients with high grade serous malignancies. ID1 is known to be associated with more invasive features of cancer and with the EMT. In our cohort, its expression is correlated with some EMT-regulators, as ECAD and SLUG (p &lt; 0,005).

Conclusions

ID proteins expression is frequently deregulated in EOC patients and it seems to influence clinical prognosis, mainly, ID1. Their usefulness as prognostic biomarkers should be further investigated in larger series.

Citation Format: Victoria Heredia, Andres Redondo, Jorge Barriuso, Alberto Berjón, Cristian Perna, Patricia Cruz, Alicia Hernández, Javier de Santiago, Esther Díaz, María Miguel, Beatriz Castelo, Laura Yébenes, Jaime Feliú, David Hardisson, Marta Mendiola. Inhibitor of differentiation-1 (Id1) expression correlates with epithelial-mesenchymal transition (EMT)-related proteins in epithelial ovarian cancer (EOC) and constitutes a novel prognostic factor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4838. doi:10.1158/1538-7445.AM2015-4838