Overexpression of ODF1 in Gastrointestinal Tract Neuroendocrine Neoplasms: a Novel Potential Immunohistochemical Biomarker for Well-differentiated Neuroendocrine Tumors

Gastrointestinal tract neuroendocrine neoplasms (NENs) are a group of rare heterogeneous tumors with different prognoses. The 2019 WHO classification of digestive system tumors defines the classification of NENs as neuroendocrine tumors (NETs G1-G3) and neuroendocrine carcinomas (NECs). We investigated outer dense fiber of sperm tails 1 (ODF1) expression in 137 gastrointestinal tract NENs including 53 NETs G1, 29 NETs G2, 3 NETs G3, and 52 NECs. Twenty adenocarcinomas and 6 squamous cell carcinomas also were included in the study. The results showed that ODF1 was positive in 83 of 85 (97.6%) primary gastrointestinal tract NETs, including 9 of 10 (90%) gastric, 19 of 19 (100%) small bowel, 10 of 11 (90.9%) colorectal, and 45 of 45 (100%) appendiceal neoplasms. There was a significantly statistical difference in the rates of ODF1 positivity in NETs (83/85, 97.6%) vs NECs (25/52, 48.1%, P < 0.001). ODF1 showed diffuse staining in NETs G1 (53/53, 100%) and NETs G2 (28/29, 96.6%), > 50% staining in NETs G3 (2/3, 66.7%), and focal staining (< 50%) in NECs (23/52, 44.2%) but 2 cases (2/52) showed > 50% staining. ODF1 showed no expression in all 20 adenocarcinomas and 6 squamous cell carcinomas. In conclusion, ODF1 was firstly identified as a novel marker for NENs, especially for NETs in the gastrointestinal tract. The expression mechanism and clinical significance of ODF1 in NENs needed further study.