P16INK4a Expression in Undifferentiated Carcinoma of the Uterus Does Not Exclude Its Endometrial Origin
Bibliographic record
Abstract
Undifferentiated carcinoma of the endometrium is a rare neoplasm, which, when involving the cervix, raises a question about its origin. Diffuse p16 positivity of uterine cancers is usually interpreted as a surrogate marker for high-risk human papilloma virus and favors cervical origin. In this study, we investigated the expression of cytokeratin 7 (CK7), monoclonal carcinoembryonic antigen (mCEA), estrogen receptor (ER), vimentin, and p16 in 28 cases of undifferentiated endometrial carcinoma, 20 high-grade endometrioid adenocarcinomas, and 50 cervical adenocarcinomas. Staining was considered positive when it was cytoplasmic for CK7, mCEA, and vimentin, nuclear for ER, and both nuclear and cytoplasmic for p16. Percentages of cells staining were recorded as follows: negative (0%-5%), 1+ (6%-25%), 2+ (26%-50%), 3+ (51%-75%), and 4+ (>75%). P16 was considered positive if it stained more than 75% of the tumor cells. Diffuse/strongly positive staining for p16 was seen in 40/50 (80%) cases of cervical adenocarcinoma and 14/28 (50%) cases of undifferentiated endometrial carcinoma. In high-grade endometrioid adenocarcinoma, staining was mainly patchy. CK7, mCEA, ER, progesterone receptor, and vimentin staining in undifferentiated endometrial carcinoma was as follows: 10/28 (36%), 4/28 (14%), 21/28 (75%), 23/28 (82%), and 26/28 (93%), respectively; for high-grade endometrioid carcinoma: 20/20 (100%), 1/20 (5%), 17/20 (85%), 18/20 (90%), and 19/20 (95%); for endocervical adenocarcinoma: 50/50 (100%), 45/50 (90%), 9/50 (18%), 8/50 (16%), and 6/50 (12%), respectively. Our data indicate that p16 may play a role in the tumorigenesis of a subset of undifferentiated endometrial carcinoma. In the setting of p16 positivity, undifferentiated endometrial carcinomas are more likely to be ER, progesterone receptor, and vimentin positive and mCEA negative when compared with endocervical adenocarcinomas. Distinction between undifferentiated endometrial carcinoma and endocervical adenocarcinoma, both of which can share diffuse p16 expression, should rely on detection of human papilloma virus in the latter.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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 teacher head, 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".