A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix: Analysis of 37 cases

Gynecol Oncol. 2017 Feb;144(2):384-390. doi: 10.1016/j.ygyno.2016.11.020. Epub 2016 Nov 28.


Objective: High-grade neuroendocrine carcinoma of uterine cervix (HGNCUC) has been recognized as a highly malignant tumor. Therapeutic strategy specific to neuroendocrine (NE) tumors needs to be considered, but some cases wouldn't allow simple final diagnoses. Insulinoma-associated protein 1 (INSM1), which is a zinc-finger transcription factor related to NE differentiation, is frequently expressed in NE tumors. We investigated the association between INSM1 and HGNCUC, and the possibility of INSM1 as a useful NE marker.

Methods: Thirty-seven cases of formalin-fixed and paraffin-embedded HGNCUCs were evaluated immunohistochemically for conventional NE markers and INSM1. We also surveyed polymerase chain reactions and examined the frequency and the genotype of human papillomavirus (HPV) infections.

Results: In HGNCUC, chromogranin A, synaptophysin and neural cell adhesion molecule (NCAM) were expressed in 86%, 86% and 68%, respectively. In addition, INSM1 was detected in 95%. Positivity for INSM1 was clearly evaluated histologically, because the intensity of nuclear staining on positive cells was high and nonspecific reactions were minimal. In uni- and multivariate analyses of prognostic factors on stage I and II surgical cases, the association between INSM1 expression and prognosis was insignificant. We confirmed 72% of 29 examined cases had high risk HPV infections (type 16, 14%; type 18, 86%).

Conclusions: This study has clarified that INSM1 is closely related to the development of HGNCUC, and a useful new NE marker in conducting its correct and rapid diagnosis.

Keywords: Cervical cancer; Human papillomavirus; INSM1; Insulinoma associated protein 1; Neuroendocrine carcinoma; Small cell carcinoma.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Carcinoma, Neuroendocrine / chemistry
  • Carcinoma, Neuroendocrine / diagnosis*
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunohistochemistry
  • Papillomaviridae / genetics
  • Repressor Proteins / analysis*
  • Uterine Cervical Neoplasms / chemistry
  • Uterine Cervical Neoplasms / diagnosis*


  • Biomarkers, Tumor
  • Repressor Proteins
  • INSM1 protein, human