1630P - Genomic characterization of early stages of ovarian cancer with emphasis in low-grade endometroid and low-grade serous histologies. A study by Span...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Ovarian Cancer
Pathology/Molecular Biology
Presenter Ignacio Romero
Citation Annals of Oncology (2014) 25 (suppl_4): iv564-iv573. 10.1093/annonc/mdu359
Authors I. Romero1, J.A. Lopez Guerrero2, J. Palacios3, B. Ojeda4, C. Illueca5, A. Gutierrez Pecharromán3, S. Blanch1, E. Cristóbal3, M.Z. Garcia Casado2, B. Vieites6, I. Ruiz Díaz7, F.J. Vera Sempere8, F. Pastor9, E. Andrada10, M. Culubret11, D. Hardisson12, E. Calvo13, C. Churruca14, A. Santaballa15, A.M. Poveda1
  • 1Area Clinica De Oncologia Ginecologica, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 2Laboratory Of Molecular Biology, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 3Pathology And Molecular Biology Department, Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 4Medical Oncology, Hspital Sant Pau, 08023 - Barcelona/ES
  • 5Department Of Pathology, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 6Department Of Pathology, Hospital Virgen del Rocío, Sevilla/ES
  • 7Department Of Pathology, Hospital de Donostia, San Sebastián/ES
  • 8Department Of Pathology, Hospita Universitario La Fe, Valencia/ES
  • 9Department Of Pathology, Hospital Morales Meseguer, Murcia/ES
  • 10Department Of Pathology, Hospital General de Elche, Eleche/ES
  • 11Department Of Pathology, Consorci Sanitari de Terrasa, Terrasa/ES
  • 12Department Of Pathology, Hospital Universitario La Paz, Madrid/ES
  • 13Departmet Of Medical Oncology, Hospital Universitario Virgen del Rocio, Sevilla/ES
  • 14Department Of Medical Oncology, Hospital de Donostia, San Sebastián/ES
  • 15Department Of Medical Oncology, Hospital Universitari i Politècnic La Fe, 46026 - Valencia/ES

Abstract

Aim

Early-stage (FIGO stage I/IIB) ovarian carcinoma (ESOC) represents 15% of all ovarian cancers and the molecular characterization of their different histologies has not been clearly defined. The aim of this study is to measure genomic abnormalities on a series of ESOCs to identify molecular alterations that influence pathophysiology, prognosis and constitute therapeutic targets.

Methods

A centralized pathological review of 573 primary ESOC was performed from samples belonging to the GEICO ESOC Registry. A series of 31 formalin-fixed and paraffin-embedded (FFPE) low-grade endometrioid (LGE) and 15 two-tier low-grade serous (LGS) ESOC were selected for analyses. Recurrence was reported in 6 of the 46 analyzed cases. Transcriptome analyses was performed in 36 cases (12 LGS and 24 LGE) using the GeneChip® Human Transcriptome Array 2.0 (Affymetrix). Whole genome copy number variations (CNV) was analyzed in the 46 cases with the OncoScanTM FFPE Assay Kit (Affymetrix).

Results

Expression analyses showed 227 genes differentially expressed (fold change >2.0 and p<0.05) between LGS and LGE ESOC and 24 genes between non-recurrent and recurrent primary tumors. Among these genes, members of the secretoglobin family (SCGB1D4, SCGB2A1 and SCGB1D2) are consistently overexpressed in LGE, SCGB2A1 being overexpressed in recurrent tumors (p<0.001), suggesting a potential role as prognostic biomarker. Specific CNV alterations were found (aggregate % cut-off 35; p-value cut off <0.05) in LGE including gains: 1q21.1, 1q22-23, 1q44, 3q26.1, 7p22.3-q31, 8p23.2, 8q11.1, 8q21.2-q23.2, 12p12.2; and losses: 22q11.23. In LGS only significant losses where observed in 22q12.2. Comparing recurrent and non-recurrent ESOC (differential threshold 25%; p-value threshold <0.001) gains at 9p24.1, 9p21.3, 9p13.3 and a loss at 22q13.2 were observed in 83% of recurrent tumors vs. 5-10% of non-recurrent.

Conclusions

Our study demonstrates the genomic heterogeneity of LGE and LGS ESOC and provides clues for the identification of potential new biomarkers that could be used as prognostic or therepeutic targets in specific biotypes of ESOC.

Disclosure

All authors have declared no conflicts of interest.