565P - A bar code of selected gene copy number alterations is associated with disease-free survival in stage II-III microsatellite stable (MSS) colon cancer

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Colon Cancer
Pathology/Molecular Biology
Translational Research
Presenter Frederic Di Fiore
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors F. Di Fiore1, L. Armengol-Debeir2, F. Blanchard3, C. Chapusot4, B. Tournier4, R. Sesboué5, D. Sefrioui2, P. Basile2, A. Gangloff2, M. Hebbar6, M. Copin7, C. Vasseur5, J. Tuech8, T. Vermeulin9, E. Houivet9, T. Frebourg5, J. Sabourin3, C. Lepage10, P. Michel2
  • 1Digestive Oncology Unit And Department Of Medical Oncology, C.H.U. Charles Nicolle and Centre Henri Becquerel, FR-76000 - Rouen/FR
  • 2Digestive Oncology Unit, C.H.U. Charles Nicolle, FR-76000 - Rouen/FR
  • 3Department Of Pathology, C.H.U. Charles Nicolle, FR-76000 - Rouen/FR
  • 4Department Of Pathology, C.H.U. Dijon, FR-21079 - Dijon/FR
  • 5U1079, Rouen University, FR-76000 - Rouen/FR
  • 6Department Of Medical Oncology, C.H.U. Lille, FR-59000 - Lille/FR
  • 7Department Of Pathology, C.H.U. Lille, FR-59000 - Lille/FR
  • 8Department Of Surgery, C.H.U. Charles Nicolle, FR-76000 - Rouen/FR
  • 9Department Of Biostatistics, C.H.U. Charles Nicolle, FR-76000 - Rouen/FR
  • 10Department Of Gastroenterology, C.H.U. Dijon, FR-21079 - Dijon/FR

Abstract

Aim

Genomic quantitative alteration is a backbone event during the carcinogenesis process in microsatellite stable colon cancer. However, the prognostic value of loss or gain of the main genomic regions is still controversial. We conducted a prospective study to assess the prognostic impact of the main genomic quantitative alterations in stage II-III MSS colon cancer (NCT02110329).

Methods

Patients treated for stage II-III colon cancer from 01/2002 to 01/2009 with available frozen tissue were included. The Quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF) method was used for molecular screening (1). The QMPSF was based on the simultaneous amplification, from normal and tumoral tissues, of 8 selected target genomic sequences according to literature data: DCC (18q21); EGFR (7p12); TP53 (17p13.1); BLK (8p23-p22); MYC (8q24.12); APC (5q22.2); ERBB2 (17q12); STK6 (20q13.31); and two control: PCBD2 (5q31.1); HMBS (11q23.3). The primary end-point was to determine the association between molecular alterations and disease-free survival (DSF). Combinations of alterations were defined according to univariate results (p < 0.15) and were tested for DFS in a multivariate analysis adjusted on stage, age, sex and differentiation.

Results

A total of 401 patients were included with a median follow-up of 48 months. There were 236 stage II and 165 stage III and the recurrence rate was 30.2%. Loss of DCC/18q, TP53/17p, BLK/8p, and APC/5q were detected in respectively 33.2%, 26.7%, 22.7%, 9.7% and gain of EGFR/7p, MYC/8q, ERBB2/17q and STK6/20q were observed in 31.7%, 35.7%, 18.7% and 48.9% of cases, respectively. There was no significant interaction between alterations and disease stage. DFS was significantly associated with loss of DCC/18q (57.5 vs 70.6%, p = 0.02) with a trend for BLK/8p loss (59.8 vs 68.6%, p = 0.08) and ERBB2/17q gain (59.2 vs 68.5%, p = 0.14). In multivariate analysis, the combination of loss DCC/18q and/or loss BLK/8p and/or gain ERBB2/17q was significantly associated with DFS. The DFS significantly decreased from 74.2% to 61.7% (HR = 1.78, 95CI: 1.14-2.77) and to 57.2% (HR =2.06, 95CI: 1.26-3.37) in patients with respectively none, 1 and at least 2 of these 3 alterations.

Conclusions

Combination of DCC/18q, BLK/8p and ERBB2/17q gene copy number alterations is associated with disease-free survival in stage II-III colon cancer.

Disclosure

All authors have declared no conflicts of interest.