HASH1 is a specific immunohistochemical marker for lung neuroendocrine tumors

Summary Mammalian/human achaete-scute homolog 1 (hASH1) regulates neuroendocrine cell development. No detailed comparative study has been conducted to explore the immunohistochemical utility of hASH1 in distinguishing different types of lung cancers. We investigated the expression of hASH1, synaptophysin, chromogranin, and CD56 in 101 squamous cell carcinomas (SCCs), 183 adenocarcinomas (ADCs), 37 typical carcinoids (TCs), 14 atypical carcinoids (ACs), 11 large cell neuroendocrine carcinomas (LCNECs), and 24 small cell lung carcinomas (SCLCs) of the lung by immunohistochemical staining with a monoclonal antibody against hASH1. Staining intensity was graded from 0 to 3, and percentage of tumor cells in each grade was estimated. All cases of ADC and SCC were discreetly negative for hASH1 in contrast to their low percentage positivity for synaptophysin, chromogranin, and CD56. hASH1 positively stained TC (64.9%), AC (64.3%), LCNEC (72.7%), and SCLC (79.2%) as did chromogranin (TC, 100%; AC, 78.6%; LCNEC, 9.0%; and SCLC, 4.2%), synaptophysin (TC, 100%; AC, 78.6%; LCNEC, 81.8%; and SCLC, 83.3%), and CD56 (TC, 59.5%; AC, 57.1%; LCNEC, 36.4%; and SCLC, 79.2%). TC and AC often showed weaker intensity and lower percentage of tumor cells positive for hASH1 (median score, 5) than LCNEC and SCLC (median score, 40 and 170, respectively). There were statistically significant differences in mean intensity scores between SCLC (148.8 ± 20.1) and other neuroendocrine tumors: TC (37.1 ± 9.2) and AC (28.6 ± 10.8) or LCNEC (51.8 ± 18.0). Our findings indicate that hASH1 is a specific marker to distinguish neuroendocrine tumors from SCC and ADC. Additionally, hASH1 is a useful diagnostic marker for segregating SCLC from other neuroendocrine tumors.