The Vascular Density/Angiogenesis Marker CD31/PECAM1 does not Correlate with Overall Survival in Neuroendocrine...

Neuroendocrine neoplasms (NENs) are rare cancers. CD31/PECAM1 is an adhesion molecule that modulates endothelial cell-to-cell contact. Increased CD31 expression is a marker for tumor growth, and cancer aggressiveness. The purpose of this study was to better understand the prognostic value of CD31 expression in primary and metastatic NEN tumors in terms of correlations with overall survival and pathological metrics, tumor grade, and tumor primary/metastatic location. As NENs are highly vascular tumors, the hypothesis is that CD31 staining is an important prognostic biomarker and target. This is based on prior correlations between CD31 staining and 3-year recurrence-free survival in pancreas NENs.

NEN tumors, surgically removed within our dedicated multi state southern regional neuroendocrine program, are routinely stained for CD31. Quantification of CD31 staining was performed by staff pathologists and documented in the pathology report within the patient medical record and stored in the rare cancer program RedCap database. The database covers surgical activity between 2004 and 2024. The database was queried for NET patients with quantified CD31 levels (number of positive vessels per high power field (HPF)) in primary or metastatic NEN tumors. CD31 levels were cross referenced against demographics, tumor grade, primary and metastatic tumor location, and overall survival.

Nine hundred and thirteen NET patients were identified. Primary tumor: Small Bowel (74%), Pancreas (15%), Lung (2%), Stomach (5%), & Rectum (4%).

Female 59±8.6%, Non-Hispanic 93.4±2%, White/Caucasian 70.4±14.3%, & Black/African American 21.6±16%. Grade: G1 45±8%, G2 44±3.6, G3 11±5.8%. There were no statistical differences in CD31 staining levels (cells/HPF) between (1) NEN tumors from small bowel (33 ± 17), pancreas (39.7 ± 34), lung (44 ± 27), stomach (39 ± 27), and rectum (32 ± 19) (p > 0.05), (2) tumor grade (G1. 31 ± 16; G2. 30 ± 16; and G3. 25 ± 12) (p > 0.05), (3) between matched primary and metastatic tumors (lymph node metastasis. 29 ± 16 vs. primary tumor 30 ± 14 (p = 0.46); liver metastasis 30 ± 18 vs. primary tumor 32 ± 17 (p = 0.17), & (4) no correlation between CD31 staining and overall survival (r = 0.01).

NEN tumors are highly vascularized and consistently positive for CD31. Despite reports that CD31/PACAM1 is important to cell adhesion and tumor phenotype, there was no identifiable measurable impact of high CD31 levels on NEN. Nor was there a prognostic clinical value for CD31 staining quantification.