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.
目的： 探讨卵巢高级别浆液性癌（high-grade serous carcinoma，HGSC）中具有实性、内膜样和移行细胞样生长方式（solid，endometrial-like，transitional，SET）亚型的临床病理学特征。 方法： 收集南京医科大学附属苏州医院2020年1月至2024年3月诊治的25例HGSC-SET的临床资料，分析其组织学形态特征。采用免疫组织化学EnVision法染色分析雌激素受体（ER）、孕激素受体（PR）、PAX8、WT-1、p16、p53和Ki-67的表达。运用二代测序法检测乳腺癌易感基因1/2（breast cancer susceptibility gene，BRCA1/2）基因突变、同源重组修复缺陷（homologous recombination deficiency，HRD）状态，及其他非BRCA同源重组修复（homologous recombination repair，HRR）基因的改变情况。并进一步比较HGSC-SET与对照组20例经典型HGSC患者的HRD状态差异。 结果： 25例HGSC-SET患者年龄41~81岁，平均年龄59岁，中位年龄57岁。4例为绝经前，21例为绝经后。12例为双侧卵巢肿物，13例为一侧卵巢单发。21例术前血清CA125升高，2例术前血清CA19-9升高。9例伴淋巴结受累，15例伴远处播散或转移，10例腹腔积液中可查见肿瘤细胞。所有病例组织形态均为混合型，既有经典型成分（乳头或微乳头、裂隙样），又有SET成分。SET成分的比例总计均>25%。15例伴粉刺样/地图状坏死。SET形态肿瘤成分对周围组织的浸润形似推挤性浸润，经典型肿瘤成分为侵袭性浸润。免疫表型，25例HGSC-SET中p53全部呈突变型表达，其中20例提示错义突变，5例提示无义突变。PAX8阳性率100%（25/25）；WT-1阳性率84%（21/25）；p16阳性率92%（23/25）。ER在SET形态区域阳性率80%（20/25），在经典形态区域阳性率68%（17/25）。PR在SET形态区域阳性率16%（4/25），在经典形态区域阳性率32%（8/25）。Ki-67在SET形态区域阳性指数60%~95%，在经典形态区域阳性指数20%~90%。分子病理学特征，36%（9/25）的HGSC-SET患者检测到BRCA1/2基因突变。其中2例为BRCA1基因突变，6例为BRCA2基因突变，1例为BRCA1及BRCA2均检测到基因突变。84%（21/25）的患者HRD为阳性；16%（4/25）的患者HRD为阴性。BRCA1/2野生型病例HRD阳性比例为12/16。共有21例患者检出了除BRCA1/2以外的HRR相关基因改变。经典型HGSC患者BRCA1/2基因突变比例为4/20，HRD阳性比例为11/20。 结论： HGSC-SET组织学形态上均为混合型，多数具有地图样/粉刺样坏死。其BRCA1/2突变率和HRD阳性率均高于经典型HGSC。BRCA1/2野生型HGSC-SET也存在较高的HRD阳性率，除BRCA1/2以外的其他HRR相关基因突变不容忽视，以免遗漏可能从PARP抑制剂治疗方案中获益的患者。.