Abstract
Abstract The prevalence of ALK gene alterations for targeted therapy with specific inhibitors is a largely unexplored issue in pulmonary sarcomatoid carcinoma (PSC), a life-threatening tumor subset whose treatment still is disappointing. ALK gene status by fluorescence in situ hybridization (FISH) and protein expression by immunohistochemistry (IHC) were carried out on formalin-fixed, paraffin-embedded material from 34 PSC. Fifty-one consecutive metastatic lung adenocarcinomas (MELAD) were also assessed in parallel for ALK with both FISH and IHC. While no rearrangements of ALK gene were detected in PSC, relevant amplification was identified in 6/34 (18%) tumors, while other genes known to behave as driver mutations according to an oncogene addiction criterion, such as EGFR, KRAS, HER2, BRAF, PIK3CA and CTNNB1, were consistently lacking. The percentage of amplified tumor cells ranged from 11% to 43%, with a mean gene copy gain (GCG) ± standard deviation (SD) of 7.5 ± 1.5. We have also investigated 51 MELAD observing that, while 10 of them showed the expected ALK rearrangement (p=0.012), only 1/51 showed the gene amplification (p=0.015). No cases of ALK-amplified tumors, either PSC or adenocarcinoma, expressed the relevant protein, whereas it was otherwise detectable in all ALK-rearranged adenocarcinomas. Interestingly all ALK-amplified tumors, either PSC or adenocarcinoma, showed also c-MET amplification consisting of variably sized clusters of specific signals, whereas negative tumors, regardless of histology, and ALK-rearranged adenocarcinomas did not show c-MET alteration. ALK and c-MET gene amplification clustered into a significant subset of elderly, smoking, predominantly male PSC patients, revealing significant differences with lung adenocarcinoma These encouraging data, however, need to be reinforced on a wider series of tumors in order to elucidate this issue, which could potentially lead to a truly effective treatment of these so life-threatening tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-437. doi:1538-7445.AM2012-LB-437
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