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

• Published in: Biomarkers Vol. 16; no. 4; pp. 311 - 320
• Main Authors: Petrovi, Marina, Baski, Dejan, Bankovi, Dragi, Ili, Nevenka
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.06.2011; Taylor & Francis
• Subjects: Adult; Aged; Biomarkers, Tumor - analysis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cell Differentiation; chemotherapy; Chromogranin A - analysis; Cisplatin - therapeutic use; Drug Resistance, Neoplasm; Female; Humans; lung cancer; Male; Middle Aged; Neuroendocrine Cells - chemistry; Neuroendocrine Cells - pathology; neuroendocrine markers; Neuroendocrine Tumors - drug therapy; Neuroendocrine Tumors - pathology; Nonmicrocellular; Paclitaxel - therapeutic use; Phosphopyruvate Hydratase - analysis; Prognosis; survival; Synaptophysin - analysis; therapeutic response; Treatment Outcome
• ISSN: 1354-750X; 1366-5804
• DOI: 10.3109/1354750X.2011.560281

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