Somatostatin receptors in resected hepatocellular carcinoma: status and correlation with markers of poor prognosis

Histopathology. 2017 Feb;70(3):492-498. doi: 10.1111/his.13034. Epub 2016 Nov 10.

Abstract

Aims: To investigate the status of somatostatin receptors (SSTRs) in resected hepatocellular carcinoma (HCC).

Methods and results: Transcript and protein levels of SSTR2, SSTR3 and SSTR5 were investigated, with real-time polymerase chain reaction (PCR) and manual and automated immunohistochemistry (IHC), in 53 resected HCCs and paired non-tumour tissues. SSTR1, SSTR4, SSTR5TMD4 and SSTR5TMD5 were analysed with real-time PCR. SSTR3 and SSTR5 transcripts were expressed in ~25% of HCCs, but not in adjacent non-tumour tissues. SSTR1 and SSTR2 transcripts were overexpressed in 42% and 32% of HCCs, respectively. SSTR4, SSTR5TMD4 and SSTR5TMD5 were not detected. Membrane staining for SSTR2 was detected in 38% of HCCs, whereas SSTR5 protein was detectable in only 11% of HCCs. SSTR3 protein was detected in the majority of HCCs and adjacent non-tumour liver tissues, but membrane staining was <20% of that in HCCs. The results obtained with the two IHC methods were highly correlated (P < 0.0001). Statistical analyses also showed a positive correlation between SSTR2 membrane staining and cytokeratin 19 expression (P = 0.04), serum α-fetoprotein level (P = 0.002), and poor differentiation (P = 0.05).

Conclusions: Membrane SSTR2 is detected reliably in HCCs by IHC, and is a potential therapeutic target, as it is coexpressed with markers of poor prognosis.

Keywords: SSTR2; hepatocellular carcinoma; immunohistochemistry; liver resection; prognosis; somatostatin receptors.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Receptors, Somatostatin / analysis
  • Receptors, Somatostatin / biosynthesis*

Substances

  • Biomarkers, Tumor
  • Receptors, Somatostatin
  • SSTR2 protein, human