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

Abstract

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.

Correlation of Somatostatin Receptor 2 Expression, 68Ga-DOTATATE PET Scan and Octreotide Treatment in Thymic Epithelial Tumors

“…Evidence also suggests that SSTR2 expression may be more common in early than in late tumor stages in neuroendocrine tumors. In the study by Popa et al of gastrointestinal neuroendocrine tumors, SSTR2 expression was 100% in tumors of early stage while only 56% of advanced stage tumors expressed SSTR2 (39). Interestingly, in our study SSTR2 expression was overall more commonly seen in advanced stage tumors (stages IIIA, IVA, IVB) than in stage I tumors although there was no statistically significant difference.…”

“…SSTR2 has been shown to be expressed in a subset of neuroendocrine tumors. A study by Popa et al suggested that SSTR2 expression may be more common in low grade than in high grade neuroendocrine tumors (39). That study showed that 96% of G1, 71% of G2 and only 23% of G3 tumors expressed SSTR2.…”

Mixed neuroendocrine–non‐neuroendocrine neoplasm associated with autoimmune gastritis

“…The other component was composed of small-to-large round cells with hyperchromatic nuclei forming solid nests (Figure 2C, D). As shown in Figure 3, these cells were positive for neuroendocrine markers such as chromogranin A, synaptophysin, and somatostatin receptors 2 (SSTR2) 2,6,7 and the Ki67 proliferation index was 3.8% of the cells (Figure 3C). P53 staining was negative F I G U R E 3 Immunohistochemical staining of the tumor.…”

New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

“…Tubular NETs are rare benign neoplasms with a predominant tubular growth pattern, so it is important not to misdiagnose them as adenocarcinomas[ 61 ]. Of note, goblet cell adenocarcinoma (formerly goblet cell carcinoid) is no longer considered an A-NEN[ 62 ]. Currently, we believe that this is an unusual type of adenocarcinoma with neuroendocrine differentiation.…”