180P - Predictive value of LKB1 in patients with resected non small cell lung cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Lung and other Thoracic Tumours
Translational Research
Presenter Elizabeth Fabre
Authors E. Fabre1, N. Pecuchet2, P. Laurent-Puig3, K. Pallier3, F. Le Pimpec-Barthes4, M. Riquet4, A. Cazes5, H. Blons3
  • 1Medical Oncology, Hopital Européen Georges Pompidou, 75015 - Paris/FR
  • 2Dept. Medical Oncology, Hopital Européen Georges Pompidou, 75015 - Paris/FR
  • 3Umr-s775, Université Paris Descartes, Paris/FR
  • 4Thoracic Surgery, Hopital Européen Georges Pompidou, 75015 - Paris/FR
  • 5Pathology, Hopital Européen Georges Pompidou, 75015 - Paris/FR

Abstract

Background

LKB1/STK11 is a serine threonine kinase involved in signal transduction, energy sensing and cell polarity. We tested the predictive value of STK11 inactivating mutations in a series of resected non-small cell lung cancer (NSCLC) patients (pts).

Methods

STK11 mutations were determined in a surgical series prospectively collected, No pts had received prior induction chemotherapy. The entire coding region (exons 1-9) of STK11 including intron/exon boundaries was screened by direct sequencing. These tumors had previously been characterized for EGFR, TP53, KRAS, BRAF, PI3KCA, ERBB2 and AKT1 mutations for CDKN2A homozygous deletions and for CCND1, CCND3, CCNE1 amplifications. Prognostic factors were determined using univariate and multivariate log-rank analysis on disease-free survival (DFS) and cancer-specific survival (C-SS).

Results

Clinical genotyping was performed in 69 pts including 29 females and 41 males, histological diagnosis was adenocarcinoma in 54 cases. Tumor stage was IA (n =16), IB (n =25), IIA (n =6), IIB (n =8), or IIIA (n =14). Somatic mutations were observed: 27 (39%) TP53, 17 (24%) KRAS, 11 (16%) EGFR, 8 (11%) STK11, 1 (1%) PIK3CA, 1 (1%) ERBB2, and 0 (0%) BRAF. Cyclin amplifications were indentified in: 10 (14%) CCND1, 8 (11%) CCNE1, 9 (13%) CCND3. In 9 cases (13%) CDKN2A were homozygously deleted. STK11 and EGFR mutations were mutually exclusive. CCND3 amplifications tended to be more frequent in STK11 mutated (3/8, 38%) relative to STK11 wild type (6/61, 10%) (p = 0.06). KRAS mutations had similar rate in STK11 mutated (3/8, 38%) and STK11 wild type (14/61, 23%) (p = 0.40). STK11 mutations were more frequent in men (n= 5/8), adenocarcinoma (n = 6/8) and smokers (n= 7/8). In univariate analysis, STK11 was the only prognostic factor associated with a lower DFS (HR = 4.78 (95%CI: 0.08-0.65); p = 0.01). C-SS was lower in pts with: STK11 mutation, CCND3 amplification, stage II-III and no radiation therapy. Multivariate analysis identified STK11 mutation to be an independent negative prognostic biomarker of C-SSl [hazard ratio (HR) =4.36 (95%CI 1.18-14.78); p =0.03).

Conclusions

STK11 mutations appear as a useful biomarker that can be regarded as an independent factor for predicting the recurrence of resected NSCLC.

Disclosure

All authors have declared no conflicts of interest.