形态学和免疫浸润能否预测新诊断的高级别浆液性卵巢癌中的同源重组缺陷状态？：来自GINECO研究PAOLA-1/ENGOT-ov25试验的经验教训。
Can Morphology and Immune Infiltration Predict the Homologous Recombination Deficiency Status in Newly Diagnosed High-Grade Serous Ovarian Carcinoma?: Lessons From the PAOLA-1/ENGOT-ov25 Trial, a GINECO Study.
作者信息
Kime Amel, Bataillon Guillaume, Treilleux Isabelle, Callens Céline, Selle Frédéric, Heitz Florian, Cinieri Saverio, González-Martin Antonio, Schauer Christian, Lindahl Gabriel, Parma Gabriella, Vergote Ignace, Matsumoto Takashi, Blonz Cyriac, Canzler Ulrich, Mosconi Anna Maria, Guerra Alía Eva María, Pujade-Lauraine Eric, Genestie Catherine, Ray-Coquard Isabelle, Just Pierre-Alexandre
机构信息
From the Department of Pathology, Université Paris Cité, Faculté de Médecine Paris Cité, APHP, Centre, Hôpital Cochin, Paris, France (Kime, Just).
the Centre Hospitalier Universitaire Amiens-Picardie Site Nord, Amiens, France (Kime).
出版信息
Arch Pathol Lab Med. 2025 Aug 1;149(8):741-750. doi: 10.5858/arpa.2024-0081-OA.
CONTEXT.—: A correlation between the morphology of ovarian high-grade serous carcinomas (HGSOCs) and BRCA mutations has been previously reported.
OBJECTIVE.—: To investigate, beyond BRCA, the association between the morphology of HGSOC and the presence of homologous recombination deficiency (HRD).
DESIGN.—: We reviewed 522 of 806 cases of HGSOC from the PAOLA-1 clinical trial, including 163 cases with tumor BRCA mutation, 345 cases without tumor BRCA mutation, and 14 cases with inconclusive BRCA tests. Regarding HRD status (myChoice HRD Plus assay), 269 cases (52%) were positive (HRD+), 198 (38%) negative (HRD-), and 55 (10%) inconclusive. Morphologic analysis included tumor architecture (with more than 25% of solid, pseudoendometrioid, and transitional patterns defining a SET architecture), tumor-infiltrating intraepithelial lymphocytes (ieTILs), and tumor stromal lymphocytes (sTILs).
RESULTS.—: SET architecture (51% versus 40%, P = .02), high number of ieTILs (16% versus 8%, P = .007), and more than 10% of sTILs (27% versus 18%, P = .02) were associated with tumor BRCA mutation, mostly for tumors with a BRCA1 mutation. These criteria were also associated with HRD status: 54% versus 33% (P < .001) for SET architecture, 14% versus 6% (P = .008) for high number of ieTILs, and 27% versus 15% (P = .003) for more than 10% of sTILs. SET architecture was also significantly associated with HRD+ tumors without tumor BRCA mutation (P < .001) when compared with HRD- tumors. The combination of these 3 criteria showed high specificity (0.99; 95% CI, 0.97-0.99) but low sensitivity (0.07; 95% CI, 0.04-0.10).
CONCLUSIONS.—: The morphology of HGSOC correlates with HRD status and BRCA status but cannot substitute for molecular analysis in daily practice.
背景
先前已有报道卵巢高级别浆液性癌（HGSOC）的形态与BRCA突变之间存在相关性。
目的
除BRCA外，研究HGSOC的形态与同源重组缺陷（HRD）的存在之间的关联。
设计
我们回顾了PAOLA-1临床试验中806例HGSOC病例中的522例，包括163例肿瘤BRCA突变病例、345例无肿瘤BRCA突变病例和14例BRCA检测结果不确定的病例。关于HRD状态（myChoice HRD Plus检测），269例（52%）为阳性（HRD+），198例（38%）为阴性（HRD-），55例（10%）结果不确定。形态学分析包括肿瘤结构（超过25%的实性、假子宫内膜样和移行模式定义为SET结构）、肿瘤浸润上皮内淋巴细胞（ieTILs）和肿瘤基质淋巴细胞（sTILs）。
结果
SET结构（51%对40%，P = 0.02）、ieTILs数量多（16%对8%，P = 0.007）和sTILs超过10%（27%对18%，P = 0.02）与肿瘤BRCA突变相关，主要是BRCA1突变的肿瘤。这些标准也与HRD状态相关：SET结构为54%对33%（P < 0.001），ieTILs数量多为14%对6%（P = 0.008），sTILs超过10%为27%对15%（P = 0.003）。与HRD-肿瘤相比，SET结构也与无肿瘤BRCA突变的HRD+肿瘤显著相关（P < 0.001）。这3个标准的组合显示出高特异性（0.99；95% CI，0.97 - 0.99）但低敏感性（0.07；95% CI，0.04 - 0.10）。
结论
HGSOC的形态与HRD状态和BRCA状态相关，但在日常实践中不能替代分子分析。
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