Clinical relevance of neuroendocrine differentiation in non-small cell lung cancer assessed by immunohistochemistry: a retrospective study on 405 surgically resected cases

Neuroendocrine differentiation in non-small cell lung cancer is a common feature, which has caused contradictory conclusions concerning survival estimates and responsiveness to therapy. Aiming to clarify this conflict, we analyzed neuroendocrine differentiation by immunohistochemistry in 405 surgically resected non-small cell lung carcinomas using standardized tissue microarray platform and the currently recommended antibody panel consisting of chromogranin-A, synaptophysin, and neural-cell adhesion molecule. Diagnostic criteria provided by the World Health Organization were applied. Histological subtypes were primarily reclassified according to current guidelines, assisted by auxiliary immunohistochemistry. Extensive clinical data was acquired, enabling detailed clinicopathological correlation. Importantly, neuroendocrine differentiation assessed by immunohistochemistry showed no significant relation to overall survival estimates, which remained unaffected by histological subtype, neuroendocrine marker type, adjuvant therapy, and recurring disease. The only exception was a small group consisting of three large cell carcinomas, each expressing all three neuroendocrine markers and demonstrating decreased survival. In conclusion, additional immunohistochemical detection of neuroendocrine differentiation in non-small cell lung cancer is presently not of prognostic importance and does not justify a distinct consideration.