The new WHO classification of gastrointestinal neuroendocrine tumors and immunohistochemical expression of somatostatin receptor 2 and 5

Exp Ther Med. 2021 Oct;22(4):1179. doi: 10.3892/etm.2021.10613. Epub 2021 Aug 13.


The 2019 World Health Organization (WHO) classification of gastrointestinal tumors defines well-differentiated grade 3 neuroendocrine tumors, the mixed neuroendocrine-non-neuroendocrine tumors (MiNENs) and classifies goblet cell carcinoid as goblet cell adenocarcinoma. The expression of somatostatin receptors (SSTRs) is the foundation for somatostatin analogue therapy. At present, there are only a few studies that have analyzed the immunohistochemical reactivity of SSTRs in gastrointestinal neuroendocrine neoplasms (NENs). The aim of the present study was to evaluate the immunohistochemical expression of SSTR2 and SSTR5 in gastrointestinal NENs and goblet cell adenocarcinomas and the correlation of these markers with clinical and morphological factors. The study included 67 patients with NENs and 4 patients with adenocarcinoma ex-goblet cell carcinoid diagnosed between January 2008 and December 2018. Tumors were reclassified according to the 2019 WHO classification. Immunohistochemical staining for chromogranin A, synaptophysin, Ki-67, p53, SSTR2, and SSTR5 were performed in all the cases. The results showed that, G1 and G2 neuroendocrine tumors were more common SSTR2-positive in comparison with G3 carcinomas (P<0.0001). In addition, 33.3% of neuroendocrine carcinomas and 2 cases of low-grade adenocarcinoma ex-goblet cell carcinoid were SSTR2-positive. Neuroendocrine carcinomas had significantly lower SSTR2 and SSTR5 expression compared with well-differentiated neuroendocrine tumors (P=0.0130; P=0.0437, respectively). The SSTR2 expression in the early tumor stages was 100%, more often than in advanced stages (55.6%; P=0.0011). The results demonstrated the decrease in SSTR2 expression with increasing malignancy and tumor stage. The SSTR2-positive expression in neuroendocrine carcinomas and adenocarcinoma ex-goblet cell carcinoid provides evidence for the benefits of somatostatin analog treatment associated with surgery and chemotherapy.

Keywords: adenocarcinoma ex-goblet cell carcinoid; chromogranin A; mixed neuroendocrine non-neuroendocrine tumor; neuroendocrine; somatostatin receptors; synaptophysin.

Grants and funding

Funding: No funding is received.