Anaplastic carcinoma of the ovary: A single-institution experience and molecular analysis

Abstract

Objective

We describe a tertiary referral center's experience with anaplastic ovarian carcinoma and characterize the genetic landscape of these rare tumors.

Methods

Anaplastic ovarian carcinomas were retrospectively identified from institutional databases from 2013 to 2023. Clinical data and survival outcomes were abstracted from the electronic medical record. Molecular data were obtained from clinical tumor-normal panel sequencing.

Results

Thirteen tumors were identified; 12 (92 %) were associated with or arose from a mucinous carcinoma, and 6 (46 %) were found in a mural nodule. Median age at diagnosis was 39 years (range, 19–77); 6 patients had stage I disease (3 stage IA), 1 had stage II, 5 had stage III, and 1 had stage IV. All patients underwent surgery. First-line postoperative therapy included carboplatin-paclitaxel doublet (n = 8), a 5-fluorouracil-oxaliplatin-based regimen (FOLFOX, n = 1; XELOX, n = 2), and ifosfamide/paclitaxel (n = 1). Two patients did not receive adjuvant chemotherapy for early-stage disease. Six patients had progression or recurrence; 5 had platinum-refractory disease and 1 had an initial progression-free interval of 6.8 months. For the 7 patients without recurrence, median follow-up was 79.7 months. Median overall survival for all patients was 28.1 months (range, 7.8–139.2). Five patients died of their disease. Ten patients had clinical panel sequencing, revealing recurrent somatic KRAS G12D/V hotspot mutations (8 of 10, 80 %) and genetic alterations affecting cell cycle-related genes, including TP53 (6 of 10, 60 %) and CDKN2A (6 of 10, 60 %).

Conclusions

Anaplastic ovarian carcinoma is characterized by KRAS, TP53, and CDKN2A alterations. Novel treatment approaches are needed due to the high rate of platinum-refractory disease.