Insulinoma-Associated Protein 1 (INSM1): Diagnostic, Prognostic, and Therapeutic Use in Small Cell Lung Cancer

Small cell lung carcinoma (SCLC) is an aggressive and difficult to treat cancer. Although immunohistochemistry is not mandatory for a SCLC diagnosis, it might be required, especially in small samples. Insulinoma-associated protein 1 (INSM1) is expressed in endocrine and nervous tissues during embryogenesis, generally absent in adults and re-expressed in SCLC and other neuroendocrine neoplasms. Its high specificity propelled its use as diagnostic biomarker and an attractive therapeutic target. Herein, we aim to provide a systematic and critical review on the use of INSM1 for diagnosis, prognostication and the treatment of SCLC. An extensive bibliographic search was conducted in PubMed (R) focusing on articles published since 2015. According to the literature, INSM1 is a highly sensitive (75-100%) and specific (82-100%) neuroendocrine immunohistochemical marker for SCLC diagnosis. It can be used in histological and cytological samples. Although advantageous, its standalone use is currently not recommended. Studies correlating INSM1 expression and prognosis have disclosed contrasting results, although the expression seemed to entail a worse survival. Targeting INSM1 effectively suppressed SCLC growth either as a suicide gene therapy regulator or as an indirect target of molecular-targeted therapy. INSM1 represents a valuable biomarker for a SCLC diagnosis that additionally offers vast opportunities for the development of new prognostic and therapeutic strategies.