Clinical significances of TTF-1, neuroendocrine (chromogranin, synaptophysin, CD56), and keratin (pancytokeratin, CK7, CK5/6) marker immunostaining in small cell lung cancer

Abstract

Purpose: Immunohistochemistry (IHC) markers have established a role in the pathological diagnosis of small cell lung cancer (SCLC) and especially neuroendocrine markers help to differentiate SCLC from other tumors. The study aimed to evaluate the clinical role of different IHC markers in SCLC patients. Methods: A total of 378 SCLC patients were enrolled in the study and analyzed retrospectively. TTF-1, neuroendocrine markers (chromogranin, synaptophysin, and CD56), and keratin markers (pancytokeratin, CK7 and CK5/6) were assessed. Results: CD56 had the highest expression (92.3%) followed by pancytokeratin (82.8%), TTF-1 (74.8%), synaptophysin (72.7%), chromogranin (55.6%), CK7 (54.8%), and CK5/6 (9%). No differences were observed in the expression of all markers according to the stage of the disease. Extended disease SCLC (ED-SCLC) patients with synaptophysin expression had a higher response to chemotherapy compared to those without staining (p = 0.01);on the other hand, the chemotherapy response of these patients was not significantly different when they expressed CK7 (p = 0.06). Pancytokeratin expression was associated with favorable survival in both limited disease SCLC (LD-SCLC) (p = 0.02) and ED-SCLC (p = 0.005) patients. Similarly, ED-SCLC patients with CD56 staining lived longer than those without expression (p = 0.001). The lack of synaptophysin expression in LD-SCLC patients (p = 0.06) and TTF-1 expression in ED-SCLC patients (p = 0.06) were correlated with better survival rates. Conclusion: We conclude that IHC markers, used frequently in the diagnosis of SCLC, might also be used in clinical decision-making, since they are correlated with predictive and prognostic factors for the disease.