Clinicopathologic features, molecular landscape, and prognostic implications of ovarian low-grade serous tumors with histologic transformation Journal Article
| Authors: | Chui, M. H.; Kang, E. Y.; Kahn, R. M.; Chiang, S.; Zhou, Q.; Iasonos, A.; Manning-Geist, B.; Selenica, P.; Da Cruz Paula, A.; Long Roche, K.; Weigelt, B.; Grisham, R. N. |
| Article Title: | Clinicopathologic features, molecular landscape, and prognostic implications of ovarian low-grade serous tumors with histologic transformation |
| Abstract: | Purpose: The purpose of this study was to characterize the clinicopathologic features, molecular genetic landscape, and clinical behavior of ovarian low-grade serous tumors with histologic transformation (LGS-HT) to indeterminate/high-grade carcinoma. Experimental Design: LGS-HT were retrospectively identified from an institutional cohort of patients with ovarian cancer and underwent central pathology re-review. Data on clinicopathologic characteristics, including age, stage, surgical outcomes, systemic treatments, and overall survival (OS), were collected. IHC profiling and next-generation sequencing were performed. OS comparisons were performed with our institutional cohorts of ovarian low-grade serous carcinoma (n = 109) and high-grade serous carcinoma (n = 1,672). Results: From 4,371 ovarian serous cancers, 40 (0.9%) LGS-HT were identified: 30 with synchronous low-grade and higher-grade tumor components at initial diagnosis and 10 with an ovarian low-grade serous neoplasm that recurred as a higher-grade carcinoma. The most common somatic driver mutations included TP53 (38.5%), KRAS (21.8%), NF1 (15.6%), BRAF (15.6%), and NRAS (12.5%), with coexisting TP53 and RAS/RAF mutations in 18.8% of cases. Alterations in DNA damage response genes (BRCA2, PALB2, CHEK2, ATM, NBN, and RECQL4) were identified in LGS-HT lacking TP53 genetic alterations. Synchronous low-grade and higher-grade tumor components at initial diagnosis were associated with poorer OS (median, 59.7 months) compared with low-grade serous carcinoma (median, 105.4 months; P = 0.026) and were similar to high-grade serous carcinoma (median, 48.8 months; P = 0.61). Severe nuclear atypia and the absence of RAS/RAF-driver mutations were significant adverse prognostic factors. Conclusions: LGS-HT exhibit both low-grade and high-grade morphologic and molecular features, representing an exception to the dualistic classification of ovarian serous neoplasms. The presence of a definitive high-grade carcinoma component in a low-grade serous tumor portends aggressive clinical behavior. © 2025 American Association for Cancer Research. |
| Keywords: | adult; aged; aged, 80 and over; middle aged; retrospective studies; genetics; mutation; mortality; cancer staging; neoplasm staging; cancer grading; ovarian neoplasms; pathology; retrospective study; tumor marker; cell transformation, neoplastic; ovary tumor; cystadenocarcinoma, serous; cystadenocarcinoma; high throughput sequencing; neoplasm grading; high-throughput nucleotide sequencing; very elderly; humans; prognosis; human; female; biomarkers, tumor; neoplastic cell transformation |
| Journal Title: | Clinical Cancer Research |
| Volume: | 31 |
| Issue: | 14 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-07-15 |
| Start Page: | 3084 |
| End Page: | 3095 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-3168 |
| PUBMED: | 40327333 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is M. Herman Chui -- Source: Scopus |
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