Abstract 1194: Multiplexed molecular profiling of Japanese squamous cell lung cancers.
Authors: Kenmotsu Hirotsugu , Serizawa Masakuni , Koh Yasuhiro , Isaka Mitsuhiro , Takahashi Toshiaki , Murakami Haruyasu , Shukuya Takehito , Akamatsu Hiroaki , Wakuda Kazushige , Maniwa Tomohiro , Hayashi Isamu , Endo Masahiro , Nakajima Takashi , Ohde Yasuhisa , Yamamoto Nobuyuki 
Published: August 2014

Background: Little advancement has been achieved in the development of efficacious molecular targeted therapies for squamous cell lung cancer, though great progress has been made in the treatment of lung adenocarcinoma in the past decade. However, results of comprehensive genome-wide characterization of squamous cell lung cancer have recently been reported and candidates for druggable targets were revealed. Thus it is becoming increasingly important to genotype squamous cell lung cancer as in the case of lung adenocarcinoma in which molecular profiles are incorporated into the lung cancer clinic. We conducted the Shizuoka lung cancer mutation study to analyze driver mutations in patients with thoracic malignancies and here we report the results of squamous cell lung cancer.

Methods: Based on the biobanking system in conjunction with the clinic including the pathology lab, we have developed a multiplexed mutational panel designed to assess 23 mutations in 9 genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN and HER2), EGFR, MET, PIK3CA, FGFR1 and FGFR2 amplifications, and EML4-ALK translocations using pyrosequensing plus capillary electrophoresis, qRT-PCR, and RT-PCR, respectively. These results are communicated to clinicians for assigning patients to appropriate therapy and/or clinical trials. A written informed consent was obtained upfront from all patients enrolled into this study.

Results: Between July 2011 and July 2012, sixty-eight squamous cell lung cancer patients were included in this study. Patients’ characteristics were as follows: median age (range) 72 (38-92) years; male 85%; smoker 97%; stage I/II/III/IV 18/35/26/21 %; well/moderate/poor/undetermined differentiated 6/34/40/20 %; surgically resected snap-frozen samples 46% and formalin-fixed paraffin-embedded (FFPE) samples 54%. We detected driver mutations in 47% of all cases. Mutations found: EGFR 2 (3%), KRAS 3 (4%), PIK3CA 9 (13%), NRAS 1 (1%), EGFR amplification 2 (3%), PIK3CA amplification 5 (7%), FGFR1 amplification 3 (4%). The frequency of FGFR1 amplification was much lower in our study than that in previous reports in Caucasian population. Seven patients harbored simultaneous driver mutations (EGFR + other 5 (7%), PIK3CA amplification + other 2 (3%)). Driver mutations were more frequently detected in surgically resected snap-frozen samples than in FFPE samples (65% v.s. 32%). Tumor differentiation was not significantly correlated with the presence or absence of driver mutations.

Conclusions: Driver mutations were detected in 47% of squamous cell lung cancer patients in this study. PIK3CA mutation seemed to be relatively frequent in squamous cell lung cancer as reported in other studies, while FGFR1 amplification seemed less frequent. This multiplexed mutational profiling should be incorporated into lung cancer clinic to facilitate personalized cancer medicine in patients with squamous cell lung cancer.

Citation Format: Hirotsugu Kenmotsu, Masakuni Serizawa, Yasuhiro Koh, Mitsuhiro Isaka, Toshiaki Takahashi, Haruyasu Murakami, Takehito Shukuya, Hiroaki Akamatsu, Kazushige Wakuda, Tomohiro Maniwa, Isamu Hayashi, Masahiro Endo, Takashi Nakajima, Yasuhisa Ohde, Nobuyuki Yamamoto. Multiplexed molecular profiling of Japanese squamous cell lung cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1194. doi:10.1158/1538-7445.AM2013-1194