[Solid, endometrial-like and transitional growth patterns of ovarian high-grade serous carcinoma: a clinicopathological analysis of 25 cases].

Objective: To investigate the clinicopathological characteristics of solid, endometrial-like and transitional (SET) cell growth subtype in high-grade serous ovarian carcinoma (HGSC). Methods: Clinical data of 25 cases of HGSC-SET were collected from January 2020 to March 2024 at the Affiliated Suzhou Hospital of Nanjing Medical University, and their histological features were analyzed. Immunohistochemical stains were used to analyze the expression of ER, PR, PAX8, WT-1, p16, p53 and Ki-67. Next generation sequencing method was used to detect breast cancer susceptibility (BRCA1/2) gene mutation, homologous recombination deficiency (HRD) status, and other homologous recombination repair (HRR) genes. The difference of HRD status between HGSC-SET and typical HGSC patients was further compared. Results: The age of HGSC-SET patients ranged from 41 to 81 years, with an average age of 59 years and a median age of 57 years. Four cases were premenopausal and 21 were postmenopausal. There were 12 cases of bilateral ovarian masses and 13 cases of unilateral ovarian masses. Serum CA125 was elevated in 21 patients and CA19-9 in 2 patients. Lymph node involvement was found in 9 cases, and distant dissemination or metastasis was found in 15 cases. Tumor cells were found in ascites of 10 cases. All the cases were of mixed type, with both typical components (papillae, micropapillae, and glands) and SET components. The total proportion of SET components was>25%. There were 15 cases with comedo/map-like necrosis. Most of the SET form showed pushing pattern of invasion, while the classic form showed infiltrative pattern of invasion. All 25 cases of HGSC-SET showed mutant type staining of p53, of which 20 cases indicated missense mutation and 5 cases indicated nonsense mutation. The positive rates of PAX8, WT-1 and p16 were 100% (25/25), 84% (21/25) and 92% (23/25), respectively. The positive rate of ER was 80% (20/25) in the SET morphological region and 68% (17/25) in the classic morphological region. The positive rate of PR was 16% (4/25) in the SET morphological region and 32% (8/25) in the classic morphological region. The proliferative index of Ki-67 was 60%-95% in the SET region and 20%-90% in the classic region. BRCA1/2 gene mutation was detected in 36% (9/25) of HGSC-SET patients. Among them, 2 cases had BRCA1 gene mutation, 6 cases had BRCA2 gene mutation, and 1 case had gene mutation both in BRCA1 and BRCA2. HRD was positive in 84% (21/25) of patients and negative in 16% (4/25) of patients. The positive rate of HRD in BRCA1/2 wild-type cases was 12/16. A total of 21 patients had HRR-related gene alterations other than BRCA1/2. The mutation rate of BRCA1/2 gene in HGSC-classic patients was 4/20, and the positive rate of HRD was 11/20. Conclusions: Histologically, HGSC-SET presents as a mixed pattern, with comedo/map-like necrosis in most cases. The mutation rate of BRCA1/2 and the positive rate of HRD are higher in HGSC-SET than in HGSC-classic type. BRCA1/2 wild-type HGSC-SET also has a higher HRD positive rate. Besides BRCA1/2, other HRR related gene mutations should not be ignored to avoid missing patients who may benefit from PARP inhibitor treatment.