Human pathology · 2026
Expanding the clinicopathological spectrum of BAP1 mutated ccRCC: a study of 84 cases in multi-center cohort.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wen Neng-Qiao, Peng Xing-Si, Huang Chan, Chen Feng, Wang Ding-Kang, Zheng Dan-Dan, Cao Yun
Аннотация
AIMS: Somatic BAP1 mutations drive a distinct and aggressive subtype of clear cell renal cell carcinoma (ccRCC), but its full histomorphological spectrum remains unclear due to small sample sizes in previous studies. This study aimed to comprehensively characterize BAP1-mutated ccRCC, define its morphological subtypes in a multi-center cohort.
METHODS AND RESULTS: A retrospective multi-center study was performed including 84 BAP1-mutated ccRCC cases from three cohorts, 16 from Sun Yat-sen University Cancer Center (SYSUCC), 38 from TCGA-KIRC, and 30 from CPTAC-ccRCC. Truncating mutations were the predominant BAP1 mutation type across all cohorts, accounting for 68.8% in SYSUCC, 60.5% in TCGA-KIRC, and 60.0% in CPTAC-ccRCC. Six distinct morphological subtypes were identified (Classic ccRCC, Macroacinar, Papillary, Sarcomatoid/Rhabdoid, Trabecular, and Mixed), with Macroacinar and Mixed subtypes being the most prevalent. 50% of Mixed subtype cases were a combination of Papillary and Macroacinar subtypes. All SYSUCC cases showed complete nuclear BAP1 loss in tumor cells by IHC, accompanied by predominantly diffuse-strong AMACR (P504S) immunostaining. Over 65% of cases in each cohort had high nuclear grade (G3/G4), with progression rates of 37.5% in the SYSUCC cohort, 39.5% in the TCGA-KIRC cohort, and 23.8% in the CPTAC-ccRCC cohort, respectively. For the entire cohort, the median overall survival (OS) was 73.8 months and median disease-free survival (DFS) was 63.8 months.
CONCLUSIONS: This study clarifies the clinicopathological and morphological features of BAP1-mutated ccRCC and defines six distinct morphological subtypes. These findings expand the clinicopathological spectrum of this aggressive ccRCC subset, provide a standardized morphological classification for clinical diagnosis.
METHODS AND RESULTS: A retrospective multi-center study was performed including 84 BAP1-mutated ccRCC cases from three cohorts, 16 from Sun Yat-sen University Cancer Center (SYSUCC), 38 from TCGA-KIRC, and 30 from CPTAC-ccRCC. Truncating mutations were the predominant BAP1 mutation type across all cohorts, accounting for 68.8% in SYSUCC, 60.5% in TCGA-KIRC, and 60.0% in CPTAC-ccRCC. Six distinct morphological subtypes were identified (Classic ccRCC, Macroacinar, Papillary, Sarcomatoid/Rhabdoid, Trabecular, and Mixed), with Macroacinar and Mixed subtypes being the most prevalent. 50% of Mixed subtype cases were a combination of Papillary and Macroacinar subtypes. All SYSUCC cases showed complete nuclear BAP1 loss in tumor cells by IHC, accompanied by predominantly diffuse-strong AMACR (P504S) immunostaining. Over 65% of cases in each cohort had high nuclear grade (G3/G4), with progression rates of 37.5% in the SYSUCC cohort, 39.5% in the TCGA-KIRC cohort, and 23.8% in the CPTAC-ccRCC cohort, respectively. For the entire cohort, the median overall survival (OS) was 73.8 months and median disease-free survival (DFS) was 63.8 months.
CONCLUSIONS: This study clarifies the clinicopathological and morphological features of BAP1-mutated ccRCC and defines six distinct morphological subtypes. These findings expand the clinicopathological spectrum of this aggressive ccRCC subset, provide a standardized morphological classification for clinical diagnosis.