Neuroendocrine differentiation as an indicator of chemosensitivity and prognosis in nonsmall cell lung cancer

Abstract

Context: Nonsmall cell lung cancers with neuroendocrine differentiation (NSCLC-ND) may demonstrate biologic behavior intermediate between NSCLC and small cell lung cancer (SCLC) with impact on prognosis.

Methods: We analyzed 116 consecutive patients with Stage III and IV NSCLC who were diagnosed and treated between 2001 and 2006. Using immuno-histochemical staining for neuron-specific enolase (NSE), chromogranin A (ChrA), and synaptophysin (Syn), 29 (25%) NSCLC-ND were identified.

Results: Expression of NSE was present in 22.4%, ChrA in 15.5% and Syn in 14.8% of patients with NSCLC. Therapeutic response was significantly better in the NSCLC-ND group and specimens with > 30% neuroendocrine (NE)-differentiated tumor cells showed favourable therapeutic response (P < 0.05). Multivariate binary logistic regression showed that percentage of NE positive tumor cells was a significant independent prognostic factor associated with a favourable outcome. Receiver operating characteristic (ROC) curves and areas under ROC curves confirmed that percentage of NE-differentiated tumor cells could be useful prediction factor of therapeutic response. Moreover, according to percentage of NE-differentiated tumor cells, optimal cutoffs and related sensitivities and specificities were determined for each markers.

Conclusion: Advanced-stage NSCLC with NE tumor cells are clinically less aggressive tumors. Percentage of NE-differentiated tumor cells identifies patients with favourable therapy response to paclitaxel-cisplatin

Keywords::

• Nonmicrocellular
• lung cancer
• neuroendocrine markers
• chemotherapy
• therapeutic response
• survival