Expression of CXCR4 in gastric NENs.

Abstract

e16312 Background: Gastric neuroendocrine neoplasms (gNENs) are a rare and heterogeneous group of tumors that include well-differentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs). Treatment selection and prognosis largely depend on tumor type, which is primarily determined by morphological assessment. Among currently investigated diagnostic and prognostic biomarkers, CXCR4 have attracted increasing interest; however, data regarding their expression in gNENs are scarce. Methods: Immunohistochemical evaluation of CXCR4 expression was performed on tumor specimens from 60 patients with histologically confirmed gNENs who underwent surgical treatment at the N.N. Blokhin National Medical Research Center of Oncology. The cohort included 21 patients with type 1 gastric NETs, 13 with type 3 gastric NETs, 14 with large-cell NECs, 8 with small-cell NECs, and 4 with MiNENs. According to tumor grade based on Ki-67 index, cases were classified as Grade 1 (n = 11), Grade 2 (n = 25), and Grade 3 (n = 24). CXCR4 expression levels were semi-quantitatively assessed (0/1+ vs 2+/3+). Results: In type 1 gastric NETs, the majority of cases (62%) demonstrated absent or low CXCR4 expression (0/1+). In type 3 gastric NETs, the proportion of cases with low or absent CXCR4 expression decreased to 46%, while 54% showed moderate to high expression (2+/3+). A further increase in CXCR4 expression was observed in more aggressive gNENs, with NECs exhibiting the highest frequency of 2+/3+ expression (82%). In Grade 3 NETs and MiNENs, high CXCR4 expression was not predominant, accounting for 50% and 25% of cases, respectively. Conclusions: High expression of CXCR4 appears to be a useful diagnostic tool for distinguishing well-differentiated gastric NETs from high-grade gNENs. In addition, these marker may help identify a subgroup of patients with an unfavorable prognosis in terms of survival. Further studies are warranted to clarify their prognostic significance and potential clinical utility.