Leakage-Controlled Classification of Dataset-Derived Ordinal p53-Signature Size Categories in Fallopian-Tube Immunohistochemistry.

Background and

Objectives

p53 signatures are segments of strongly p53-immunoreactive secretory epithelium in the fallopian tube. We tested whether fixed pathology-pretrained image representations could classify three ordered categories reconstructed from the public dataset's reported cell-count intervals.

Methods

The primary cohort comprised 113 canonical p53 20× fields from 67 patients: 59 Small (12-20 cells), 24 Medium (21-80), and 30 Large (>80). A 141-field partial-label cohort retained boundary-spanning intervals for sensitivity analysis. Twenty-six eligible feature/head pipelines were evaluated by three-repeat five-fold nested patient-grouped cross-validation. Within every outer fold, the pipeline was selected using inner validation only; primary performance metrics were computed within each repeat and averaged across the three repeats, while the resulting 339 held-out predictions were pooled only for the confusion-matrix visualization. Uncertainty was estimated using 2000 patient-cluster bootstrap replicates conditional on these recorded predictions.

Results

The fold-wise nested selector achieved quadratic-weighted kappa (QWK) 0.687 (95% CI 0.547-0.785), macro-F1 0.628 (0.568-0.680), balanced accuracy 0.637 (0.581-0.693), macro-AUROC 0.805 (0.750-0.855), and macro-AUPRC 0.681 (0.633-0.754). Small, Medium, and Large sensitivities were 0.870 (0.801-0.928), 0.264 (0.159-0.386), and 0.778 (0.617-0.906); severe Small-Large errors occurred in 6.5% (2.9-10.6%). Equal patient weighting gave QWK 0.700. In a secondary locked UNI2-h/CORAL analysis, ordinal temperature scaling reduced ECE from 0.195 to 0.157 and negative log-likelihood from 1.291 to 0.778.

Conclusions

Fixed representations provided useful internal discrimination of dataset-derived ordinal categories, with substantial fold variability and weak Medium-category sensitivity. The results do not validate lesion measurement, detection, diagnosis, or clinical use; independent pathologist-annotated evaluation is required.