Jornal de Biomarcadores Moleculares e Diagnóstico

The Role of NFκB, HIF-1α and Neuropeptide (ET-1) - Peptidase (CD10, NEP) Axis in Ovarian Cancer: An Immunochemistry Approach

Abstract

Perdikouri E, Liaskos C, Papacharalampous K, Nasi D, Kostopoulou E, Koukoulis G and Papandreou C

Introduction: Ovarian cancer is considered to be the leading cause of death due to gynecological malignancies. Because of lack of effective screening methods, most patients are diagnosed at an advanced stage. Therefore, there is a mandatory need to develop new markers for early detection and prognostication as well as for response to treatment and detection of disease recurrence after definitive therapy.

Aim: Our study was designed to analyse immunohistochemically the expression of transcription factors NFκB and HIF-1α, in addition to biomarkers of endothelin axis (CD-10, ETAR and ETBR) in patients with ovarian cancer and relate their expression with overall survival and response to therapy.

Methods: Ninety four samples from paraffin-embedded tissues from patients with ovarian cancer were included. The final analysis of the samples compared two cohort groups that were dichotomized to positive and negative according to histoscore (either nucleoscore or cytoscore) of each patient.

Results: Patients expressing high NFκB nuclear score, high HIF-1 α nuclear score, low CD-10 score and high ETAR and ETBR scores had worse overall survival. Moreover, platinum sensitive patients expressed lower nuclear NFκB, higher cytoplasmic HIF-1α, higher CD-10 and lower ETAR expression. NFκB cytoplasmic score and ETAR score were correlated with disease of early stage, while CD-10 histoscore was associated with advanced stages. More importantly, a combination of specific biomarkers was correlated with OS of patients.

Conclusion: Our study confirms the prognostic value of CD10 in ovarian carcinoma through its association with endothelin axis, while the last one (ET axis), mediated mainly through ETAR, may also have clinical and therapeutical impact. Finally, the nuclear expression of known transcriptional factors such as HIF-1α and NFκB could be prognostic biomarkers to assess clinical outcome and possibly predict resistance to platinum-based chemotherapy.