PAX5 expression and its diagnostic utility in gastroenteropancreatic neuroendocrine neoplasm

Abstract Background: Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) are common tumors of the digestive system. Although their histological diagnosis is usually straight forward, their differential diagnosis between neuroendocrine tumors G3(NETs G3) and neuroendocrine carcinomas (NECs) may be challenging at times. Because they have the similar immunophenotypes and morphology in a small cases. The previously reported revealed PAX5 expression in poorly differentiated neuroendocrine carcinoma of the gastrointestinal and pancreatobiliary tract, small cell carcinoma of lung and merkel cell carcinoma. However, above study only focused on poorly differentiated neuroendocrine carcinoma, cases of NET G1, G2 and G3 were not included. Aims and Methods: The objective of this study is to assess the expressed and diagnostic value of PAX5 in the GEP-NENs. Immunohistochemical(IHC) analysis for PAX5 was carried out in a large cohort of GEP-NENs comprising 39 GEP-NECs and 62 GEP-NETs. Results: Using a semi-quantitative scoring method, PAX5 was expressed in 30 out of 39 GEP-NECs (77%), with 27 out of 39 cases (69%) showing positivity in ≥10% of cells. Especially in GEP-NECs with a high proliferative index, there were more PAX5-positive cells. None of cases of GEP-NET G1 and G2 expressed PAX5. Only 2/12 cases GEP-NET G3(17%) was positive for PAX5, with showing PAX5 positivity in 1-10%% of cells and 10-50%, respectively. The difference in PAX5 expression between GEP-NETs and GEP-NECs was obviously statistically significant(3% vs. 76%, P<0.001). Conclusions: PAX5 can be used as a complementary diagnostic immunohistochemical marker for GEP-NECs. Additionally, PAX5 can be considered in cases when it is difficult to distinguish between GEP-NECs and GEP-NET G3.