How should molecular findings be integrated in the classification for lung cancer?

The use of molecular diagnostics in the diagnosis and management of patients with advanced lung cancer has become widespread. Although molecular classification has increasingly been incorporated in the pathologic classification of certain types of human tumors (particularly within the hematologic, glial, and bone/soft tissue malignancies), genetic findings have not been formally incorporated into the pathologic classification of lung cancer, which presently relies solely on the assessment of histologic and immunophenotypic characteristics. Whether molecular classification should be adopted in lung cancer would depend on the diagnostic, prognostic, and predictive impacts of such classification—and whether these impacts confer significant values additive to those derived from the routine histologic and immunophenotypic assessment. We provide a brief overview on the genetics of lung cancer, including adenocarcinoma, squamous cell carcinoma, and neuroendocrine tumors (small cell carcinoma, large cell neuroendocrine carcinoma, and carcinoid tumors). We consider the values of molecular information with some examples, in terms of the current diagnostic, prognostic, and predictive impacts. Finally, we discuss the conceptual and technical challenges of adopting a molecular classification for lung cancer in clinical management for patients. While there are conceptual and technical hurdles to tackle in implementing molecular classification in the pathologic classification of lung cancer, such integrated histologic-molecular diagnosis may allow one to personalize and optimize therapy for patients with advanced lung cancer.