Insulinoma-associated Protein 1 (INSM1) Is a Better Marker for the Diagnosis and Prognosis Estimation of Small Cell Lung Carcinoma Than Neuroendocrine Phenotype Markers Such as Chromogranin A, Synaptophysin, and CD56.

Abstract

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.

• Authors: Rie Sakakibara, Maki Kobayashi, Naoko Takahashi, Kentaro Inamura, Hironori Ninomiya, Ryo Wakejima, Satoru Kitazono, Noriko Yanagitani, Atsushi Horiike, Junji Ichinose, Yosuke Matsuura, Masayuki Nakao, Mingyon Mun, Makoto Nishio, Sakae Okumura, Noriko Motoi, Takaaki Ito, Yasunari Miyazaki, Naohiko Inase, Yuichi Ishikawa
• Journal: The American journal of surgical pathology (Am J Surg Pathol) Vol. 44 Issue 6 Pg. 757-764 (06 2020) ISSN: 1532-0979 [Electronic] United States
• PMID: 32118626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• CD56 Antigen
• Chromogranin A
• NCAM1 protein, human
• Repressor Proteins
• SYP protein, human
• Synaptophysin
• INSM1 protein, human

Topics

• Aged
• Aged, 80 and over
• Biomarkers, Tumor (analysis, metabolism)
• CD56 Antigen (analysis, metabolism)
• Chromogranin A (analysis, metabolism)
• Female
• Humans
• Lung Neoplasms (diagnosis, metabolism)
• Male
• Middle Aged
• Phenotype
• Prognosis
• Repressor Proteins (analysis, metabolism)
• Sensitivity and Specificity
• Small Cell Lung Carcinoma (diagnosis, metabolism)
• Synaptophysin (analysis, metabolism)