USCAP 2018 Abstracts: Gynecologic and Obstetric Pathology (1127–1316)
Bibliographic record
Abstract
Background: While uterine serous carcinomas (USCs) are morphologically and immunophenotypically indistinguishable from their ovarian counterparts, questions remain on whether these tumors share similar molecular profile and therefore could benefit from similar therapies.Somatic and germline defects in genes of the homologous recombinant(HR) pathway(BRCA1, BRCA2 and others) have been implicated in ovarian cancer predisposition and are associated with high sensitivity to platinum-based and targeted therapies(PARP inhibitors).HR deficiency impairs normal DNA repair resulting in loss or duplication of chromosomal regions, termed genomic loss of heterozygosity(LOH).Whether this phenomenon applies to USCs is yet to be determined.In this study, we analyzed genome-wide LOH in USCs and correlated its extent with clinicopathological parameters and survival outcomes.Design: 69 platinum treated USC patients diagnosed between 1998-2015 were included.DNA was isolated from FFPE and LOH analysis was performed querying over 220,000 SNPS using the Affymetrix OncoScan.Selecting the top quartile of LOH distribution as a cut point to separate patients into LOH "high" and LOH "low" groups, data was analyzed using KM survival analyses.Results: Patients' ages ranged from 45 -89(median 68) yrs.Stage distribution included: 11.5% I, 1.5% II, 62% III and 25% IV.Lymphadenectomy was performed in 74% and omentectomy in 62% of patients.80% of patients received adjuvant radiotherapy.Median LOH was 1.4% (range 0-30.1%) and the top quartile threshold was 9.9%.52 tumors showed LOH lower than the top quartile.In the top quartile of LOH, tumors were more common in African Americans(83% vs 56%), advanced stage(100% vs 82%) and more commonly associated with outer half MI(76.5% vs 47%) and LVI(88% vs 65%) when compared to tumors with LOH lower than the top quartile.In general, LOH did not significantly correlate with age(p=0.41),race(p=0.43),tumor size(p=0.72),stage(p=0.36),MI(p=0.52),LVI(p=0.40),LN metastases(p=0.43),or recurrence(p=0.34).KM analysis showed no survival benefit nor prolonged DFI for platinum treated patients with LOH in the top quartile compared to LOH lower than that. Conclusions:In our cohort of USCs, median LOH was 1.4%, with 25% of tumors showing genomic LOH higher than 9.9%.In contrast to their ovarian counterparts, a high degree of genomic LOH does not correlate with survival benefit for platinum treated USC patients, suggesting that these tumors may have distinct biology and genomic profile.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.004 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.478 | 0.246 |
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".