Journal
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
Volume 44, Issue 6, Pages 757-764Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/PAS.0000000000001444
Keywords
insulinoma-associated protein 1 (INSM1); achaete-scute complex homolog-like 1 (ASCL1); neuroendocrine tumor; small cell lung carcinoma (SCLC); large cell neuroendocrine carcinoma (LCNEC); carcinoid
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan [JP16K08679, JP26430149]
- Japan Society for the Promotion of Science [JP15H04714, 19H03446]
- Ministry of Health, Labour and Welfare, Japan
- Ministry of the Environment, Japan
- Japan Agency for Medical Research and Development
- Daiichi Sankyo Co. Ltd
- Roche Diagnostics
- Konica Minolta Inc.
- Grants-in-Aid for Scientific Research [19H03446] Funding Source: KAKEN
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To diagnose small cell lung carcinoma (SCLC), neuroendocrine (NE) phenotype markers such as chromogranin A, synaptophysin, and CD56 are helpful. However, because they are dispensable, SCLCs occur without apparent NE phenotypes. Insulinoma-associated protein 1 (INSM1) is a transcription factor for NE differentiation and has emerged as a single practical marker for SCLC. Using the surgical samples of 141 pulmonary NE tumors (78 SCLCs, 44 large cell NE carcinomas, and 19 carcinoids), and 246 non-NE carcinomas, we examined the immunohistochemical expression and prognostic relevance of INSM1 in association with NE phenotype markers. We evaluated its sensitivity and specificity for SCLC diagnosis, as well as its usefulness to diagnose SCLC without NE marker expression and to estimate the prognosis. INSM1 was expressed in SCLCs (92%, 72/78), large cell NE carcinomas (68%, 30/44), and carcinoids (95%, 18/19). In addition, among SCLCs with no expression of NE phenotype markers (n=12), 9 (75%) were positive for INSM1. These data suggest the superiority of INSM1 to the phenotype markers. Only 7% of adenocarcinomas (9/134) and 4% of squamous cell carcinomas (4/112) were positive for INSM1. SCLC with low-INSM1 expression (n=28) had a significantly better prognosis (P=0.040) than the high-INSM1 group (n=50). Our study revealed that INSM1 is highly sensitive and specific to detect SCLC and can estimate prognosis. INSM1 will be a promising marker for SCLC.
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