Molecular and Immune Microenvironmental Changes Across Endometrial Lesions: A Comprehensive Immunohistochemical and Clinical Analysis of Progression From Benignity to Carcinoma
Bibliographic record
Abstract
Background: Adenomyosis and endometriosis are estrogen-driven disorders with a recognized potential for malignant transformation, particularly through atypical endometriosis. The molecular and immune mechanisms underlying this progression remain incompletely understood. However, clinical factors such as age, comorbidities, and hormonal therapy can also influence lesion behavior. The objectives were to comprehensively evaluate hormonal, proliferative-apoptotic, cell-cycle, and immune-microenvironmental alterations across the spectrum of endometrial lesions and to assess the impact of prior endometrial hyperplasia and associated clinical parameters. Methods: Seventy-seven formalin-fixed paraffin-embedded cases were stratified into five groups: eutopic endometrium (n = 17), adenomyosis (n = 27), typical endometriosis (n = 16), atypical endometriosis (n = 10), and endometriosis-associated carcinoma (n = 24). Immunohistochemical analysis included estrogen receptor, progesterone receptor, Ki67, BCL2, P53, cyclin D1, CDK4, P16, FOXP3, CD68, and CD163. Clinical variables including age, comorbidities, and medication history were integrated into statistical analysis. Marker expression was quantified semi-quantitatively, and clinical associations with prior endometrial hyperplasia were evaluated using Kruskal-Wallis and Mann-Whitney U tests. Results: M2 macrophages accumulated in atypical endometriosis and carcinoma, indicating an immunosuppressive microenvironment. Patients with prior atypical endometrial hyperplasia demonstrated significantly higher expression of proliferative (cyclin D1, CDK4, and P16) and immune-suppressive markers (FOXP3 and CD163) and a 66% progression to carcinoma. Clinical background factors were statistically adjusted and did not alter the overall progression trend. Conclusion: The stepwise evolution from benign endometrial lesions to carcinoma is driven by coordinated proliferative and immune microenvironmental shifts, potentiated by a history of atypical endometrial hyperplasia. Integrating immunohistochemical and clinical risk factors may enhance early identification and surveillance of patients at high risk for endometriosis-associated carcinoma.
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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 | 0.002 | 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".