Toward personalized medicine of lung cancer: response to nontargeted therapy in invasive pulmonary adenocarcinoma as a function of tumor cell differentiation.

We evaluated clinical parameters, histomorphology, and thyroid transcription factor 1 (TTF-1) immunoreactivity in 40 epidermal growth factor receptor (EGFR) mutation- and anaplastic lymphoma kinase (ALK) rearrangement-negative invasive pulmonary adenocarcinomas. Tumors were histomorphologically quantitated by a pulmonary pathologist and TTF-1 immunohistochemistry applied. EGFR mutation and ALK rearrangement status was determined with polymerase chain reaction/DNA sequencing and fluorescence in situ hybridization, respectively. Treatment response was related to type of treatment (P < .005) and clinical stage (P = .001). EGFR mutation- and ALK rearrangement-negative pulmonary adenocarcinomas containing papillary/micropapillary histology showed greater morphologic heterogeneity (P < .001), greater TTF-1 immunoreactivity (P = .004), and were more common in treatment responders (P < .05). These findings support that patients with pulmonary adenocarcinomas that are subject to nontargeted therapies may respond to treatment as a function of tumor cell differentiation with TTF-1 as a potential biomarker of this response.