SESSION TYPE: Lung Cancer II
PRESENTED ON: Monday, October 22, 2012 at 04:00 PM - 05:30 PM
PURPOSE: To determine the mutation status of driver mutations in lung squamous cell carcinomas (LSCCs) and to re-clarify the mutation screening strategy in Chinese LSCC patients.
METHODS: Three hundred and ten surgically resected frozen LSCC specimens and corresponding FFPE tumor blocks were collected at Fudan University Shanghai Cancer Center. A combination scheme with morphological features and IHC staining was conducted to exclude misdiagnosed adenocarcinomas and adenosquamous carcinomas. All known driver mutations, like EGFR, KRAS, BRAF, HER2, PIK3CA, AKT1, DDR2, as well as EML4-ALK and KIF5B-RET rearrangements were screened using cDNA-based sequencing. For detected EGFR/KRAS mutations, a further confirmation was performed in FFPE sections using microdissection to ascertain the real mutation component. Meanwhile, detected driver mutations and rearrangement were linked to clinical and pathological features.
RESULTS: Two hundred and eighty-seven specimens, consisting of pure LSCCs and LSCCs with partial glandular component, were enrolled in mutational analysis, among which,10 EGFR mutations, 6 KRAS mutations, 1 BRAF mutation, 1 HER2 mutation, 1 AKT1 mutation, 1 DDR2 mutation, 11 PIK3CA mutations and 1 EML4-ALK fusion were identified,including1EGFR/PIK3CA and 1 KRAS/PIK3CA co-mutation. Microdissection sequencing revealed that 2 of 4 LSCC with partial glandular component specimens manifested an inconsistent mutation status between the two components. Although diagnosed as pure LSCCs by P63/TTF-1 staining, 5 of 9 specimens were failed to re-find the detected mutations, including 1 EGFR mutation and 4 KRAS mutations, which indicated that incomplete sampling or scattered glandular cells were responsible for accidently detected EGFR/KRAS mutations in pure LSCCs. Further clinical and pathological analysis showed that female, never-smoking status and peripheral location, which were usually linked with glandular component, were associated with a high mutation rate.
CONCLUSIONS: EGFR/KRAS mutations should be considered as exclusive biomarkers of adenocarcinomas. Apart from exact pathological diagnosis, female, never-smoking status and peripheral location should be considered as predictors of mutations in Chinese LSCC patients.
CLINICAL IMPLICATIONS: Our data has an important implication in mutation screening strategy for target therapy in Chinese LSCC patients.
DISCLOSURE: The following authors have nothing to disclose: Yunjian Pan, Rui Wang, Chenguang Li, Yihua Sun, Haiquan Chen
No Product/Research Disclosure InformationFudan University Shanghai Cancer Center, Shanghai, China