Phosphatidylinositol 3-kinase could be a promising target in lung cancer therapy

Purpose: To investigate the prevalence of phosphatidylinositol 3-kinase (PIK3CA) gene amplification in lung cancer, and to explore its prognostic value. Methods: A total of 647 lung tumor samples from 290 patients were included in the study. The ratio of PIK3CA signals/centromere 3 signals in cancer cells was estimated by fluorescence in situ hybridization (FISH) analysis. Results: Both gains and amplifications were significantly more frequent in squamous cell (gains: 19.4%; amplifications: 34.1%; p < 0.0001) and large cell carcinoma (gains: 22.4%; amplifications: 20.4%; p < 0.0001) compared with adenocarcinomas (gains 3.0%; amplifications: 4.0%). Conversely, adenocarcinomas displayed significantly more frequent deletions of the PIK3CA locus than the other two histologic types (p < 0.0001). No clear correlation between PIK3CA status and the pT stage, pN stage or the degree of tumor differentiation was found. Ki67 significantly increased with increasing of PIK3CA copy number: 47 tumors with a PIK3CA deletion had a mean Ki67 of 16, while 103 tumors with PIK3CA amplification showed a mean Ki67 of 28 (p=0.004). Significant association between cell proliferation and PIK3CA was found (p < 0.05). However, no significant correlation was seen between patient survival and PIK3CA amplifications, deletions and gains. Conclusion: PIK3CA amplifications in large cell and squamous cell carcinomas were significantly higher compared with adenocarcinomas. The results suggest that PIK3CA could be a promising target for selective lung cancer therapy.