895P Correlating peptidylglycine alpha-amidating monooxygenase (PAM) expression with clinicopathologic variables in gastrointestinal (GI) neuroendocrine tumors (NETs)

PAM is a protein responsible for neuroendocrine hormone maturation. Horton et al 2020, showed PAM staining intensity by immunohistochemistry (IHC) correlates with clinical and pathologic parameters in neuroendocrine neoplasms. We investigate PAM expression by IHC in patients with well-differentiated NETs exclusively of the GI tract and its correlation with clinical and pathologic variables. A tissue microarray (TMA) was constructed, with 81 punches from 29 patients with NETs of the GI tract. PAM staining was scored for intensity (range 0-3) and percent of cells staining (range 0-4), multiplying these to give an overall immunoreactive score (IRS) between 0 and 12, averaged over multiple punches from the same patient. These results were then dichotomized into 0-1 (negative) and >1-12 (positive). Patients had NETs involving the stomach (n=1), duodenum (n=1), ileum (n=14), small bowel (n=5), cecum (n=2), and pancreas (n=6). Ten patients (35%) had 1 metastatic site, 7 patients (24%) had >=2 metastatic sites and 12 patients (41%) lacked metastases. Nine patients (31%) had negative PAM staining, and 20 patients (69%) had positive PAM staining. Pancreatic (83%) and small bowel NETs (70%) were more likely to have positive staining, although not statistically significant (p = 0.33). PAM staining did not correlate with functional status of the tumor (p=1), synchronicity of disease (p=1), number of metastatic sites (p=0.69), Octreotide receptor positivity (p=0.72) or blood chromogranin A (p=0.58) and urine 5 HIAA levels (p=0.52). PAM scoring also did not correlate with Ki-67 of primary tumors (p=0.57). In our GI NET cohort, PAM staining did not correlate with any of the assessed clinical variables or with Ki-67 of primary tumors. A previous study of NETs involving more body sites found that PAM staining did inversely correlate with Ki-67 scoring. This difference may be due to our assessment of solely GI NETs, or difference in scoring system; future work will replicate the system used in the previous study to further investigate PAM as a prognostic biomarker.