In liver metastases from small intestinal neuroendocrine tumors, SSTR2A expression is heterogeneous

Virchows Arch. 2017 May;470(5):545-552. doi: 10.1007/s00428-017-2093-3. Epub 2017 Feb 17.

Abstract

We examined somatostatin receptor type 2A (SSTR2A) expression in primary and metastatic small intestinal neuroendocrine tumors (SI-NETs). We retrieved 156 liver metastases from 26 patients (10 males, 16 females) who had two or more liver lesions resected. A representative formalin-fixed paraffin-embedded section of tumor tissue from each liver metastasis and from the primary tumor, when available, were immunohistochemically stained for SSTR2A. SSTR2A expression was evaluated by the Her2/neu-scoring system and the scoring system proposed by Volante et al. Based on the Her2/neu-scoring system, moderate to strong SSTR2A expression was observed in 121 of 156 (78%) liver metastases. In 15 (58%) subjects, all liver metastases showed moderate to strong SSTR2A expression, whereas in 11 (42%) one or more liver tumors had weak or no expression. Of the 16 stained primaries, 11 (69%) showed heterogeneous SSTR2A expression. The corresponding liver metastases showed only weak to no expression in one, moderate to strong in five, and both weak to no and moderate to strong expression in five of the 11 cases. Using the Volante scoring system, no tumor was scored 0 (0%), two were scored 1 (1%), 38 were scored 2 (24%), and 116 were scored 3 (74%). No statistically significant association was observed between SSTR2A expression and Ki67 index (p = 0.56). Fifteen of 18 (83%) metastatic tumors with a Ki67 index >20% showed moderate to strong SSTR2A. Most liver tumors with weak SSTR2A expression or an IHC score of 2 were detected by OctreoScan. SSTR2A expression in liver metastases of SI-NETs can be variable, even between lesions in the same patient. Expression in metastatic lesions is not always similar to that in the primary tumor. SSTR2A expression is not associated with the Ki67 index.

Keywords: Heterogeneity; Liver metastasis; Neuroendocrine tumor; SSTR2A; Small intestine.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Female
  • Humans
  • Immunohistochemistry
  • Intestinal Neoplasms / secondary*
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Neuroendocrine Tumors / pathology*
  • Receptors, Somatostatin / analysis
  • Receptors, Somatostatin / biosynthesis*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Receptors, Somatostatin
  • somatostatin receptor 2