Impact of Non-Small-Cell Lung Cancer-Not Otherwise Specified Immunophenotyping on Treatment Outcome

Introduction: The vast majority of non-small-cell lung cancers (NSCLCs) presents as advanced disease, and histological diagnosis is widely based on small samples. The differential activity and toxicity profile of new cytotoxic and molecular-targeted therapies according to histotypes requires a precise subtyping of NSCLC. Immunohistochemistry (IHC) contributes to define the most probable histotype; however, the real impact of IHC characterization of NSCLC-not otherwise specified (NOS) in terms of outcome is not well established. Methods: A large series of 224 advanced nonsquamous NSCLC diagnosed on small biopsy or cytological samples and homogeneously treated was retrospectively selected, all having adequate follow-up data available. Reviewed diagnoses resulted into two groups: adenocarcinoma (ADC) and NSCLC-NOS. The latter was further characterized by IHC (TTF-1, Napsin-A, p40, and Desmocollin-3) -identify a possible, most probable differentiation lineage. Results: Sixty-seven percentage of cases were classified as ADC based on morphological examination only (morphological ADC) and 33% as NSCLC-NOS. IHC profiling of NSCLC-NOS identified 43.2% of cases with an ADC immunophenotype (NSCLC favor ADC), 10.8% with a phenotype favoring squamous lineage, and 46% lacking differentiation features. Survival curves confirmed no difference in terms of outcome between the morphological ADC and the NSCLC favor ADC groups, while a significantly poorer outcome was found in the null group in terms of best response, progression-free survival or overall survival (OS). Conclusion: Tumors with an IHC profile ADC-like had an OS comparable with that of morphological ADCs. These findings support the use of IHC to optimize lung cancer histological typing and therapy.