Clear Cell Carcinoma of Uterine Cervix: A Clinicopathologic Review and Molecular Characterization
Bibliographic record
Abstract
Abstract Clear cell carcinoma of uterine cervix (CCCUC) is an uncommon variant of cervical adenocarcinoma unrelated to Human Papilloma Virus (HPV). With widespread Pap test screening and HPV vaccination resulting decline in incidence of cervical HPV-related cancers, it is important to develop better understanding of the less common HPV-independent variants of cervical adenocarcinoma, including CCCUC. In this study, 10 cases of CCCUCs diagnosed over a 15 year period were retrospectively reviewed for clinicopathological and immunohistochemistry characteristics and HPV DNA PCR; and next generation sequencing (NGS) was performed in cases with available pathology material. Mean age of patients was 39.6 (range of 18–82) and all presented with vaginal bleeding. Most cases (6/10) were diagnosed at FIGO stage IIB. Eight patients had surgery, with lymph nodes dissection in 7. Adjuvant therapy followed in 5 cases. Median follow up period was 38 months. HPV DNA PCR proved negative HPV status in all cases. For immunohistochemistry, all cases showed wild-type p53 expression, positive PAX8 and HNF1β, and negative ER and PR. MMR protein expression was intact in 4 cases. Two cases had lost/equivocal MSH2/MSH6 expression, one of which proved negative for microsatellite instability in NGS. Based on combined positive score (CPS), more than half of cases with available PD-L1 (4/7) were positive. 70 genetic variants were identified in testing of tumor tissue DNA from 6 cases with an NGS panel assessing 562 cancer-associated genes for single-nucleotide and copy-number variations for selected genes, and insertions/deletions. Variants occurred most frequently in genes ATM, CDH23, CSMD3, KDM5C, LRP1B, NIN, PKHD1, and RNF213. Pathways that were enriched for genes in this data set include apoptosis regulation, cell cycle and DNA repair, PI3K-AKT signaling, and NGF signaling. Multiple genes were associated with receptor tyrosine kinase activity, chromatin remodeling, and transcriptional regulation. This is the first study to explore the genomic landscape of CCCUC using Next Generation Sequencing. Some potentially actionable molecular alterations are present in these tumors. However, genetic findings are heterogeneous and further studies with larger sample size is required to better characterize this rare malignancy and to allow development of novel diagnostic and therapeutic techniques.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| 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".