Correlating peptidylglycine alpha-amidating monooxygenase (PAM) expression with clinicopathologic variables in gastrointestinal (GI) neuroendocrine tumors (NETs).
Bibliographic record
Abstract
e16243 Background: Peptidylglycine alpha-amidating monooxygenase (PAM) is a hypoxia-responsive protein which is responsible for peptide alpha-amidation, important in neuroendocrine hormone maturation. A prior study of well-differentiated neuroendocrine tumors of multiple sites, both GI and non-GI, has shown that PAM expression by immunohistochemistry correlates with important clinical and pathologic parameters. We assessed PAM expression by immunohistochemistry using two separate scoring systems in patients with well-differentiated neuroendocrine tumors (NETs) exclusively of the GI tract and assessed its correlation with clinical and pathologic variables. Methods: A tissue microarray was constructed from 58 patients with NETs of the GI tract. Two separate scoring systems were used, the immunoreactive score (IRS) and one as described by Horton et al (2020). The IRS score was derived by scoring for intensity (range 0-3) and percent of cells staining (range 0-4), multiplying these to give an overall IRS between 0 and 12. These results were dichotomized into 0-1 (negative) and 2-12 (positive). The score as described by Horton et al is a 4-tiered system: 0, no staining; 1, very faint and scarce staining; 2, staining easily visible in > 50% of tissue; 3, moderately dark and intense staining across 50% of tissue; 4, very intense dark staining across > 50% of tissue. These were then divided into negative (0), low (1) and high (2-4) scores. Clinical and pathologic variables were collected from the clinical records and correlated with PAM staining. Results: Patients had NETs involving the stomach (n = 1), duodenum (n = 3), ileum (n = 18), small bowel (n = 12), cecum (n = 2), and pancreas (n = 13). Twenty-one patients (36.2%) had 1 metastatic site, 12 patients (20.7%) had > = 2 metastatic sites and 25 patients (43.1%) lacked metastases. IRS and Horton scores were compared and were correlated (p = 0.007). By IRS, 9 patients (31%) had negative staining, and 20 patients (69%) had positive PAM staining. 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). Conclusions: 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 gastrointestinal NETs.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".