Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Am J Surg Pathol. 2012 Aug;36(8):1170-7. doi: 10.1097/PAS.0b013e31825d9b8d.
Specific morphologic features that may predict BRCA1 germline mutation in ovarian cancer have neither been well described nor independently tested. We identified 5 morphologic features associated with BRCA1 mutation status in a series of 20 ovarian cancers from BRCA1 mutation carriers: (1) modified Nottingham grade 3; (2) serous/undifferentiated histology; (3) prominent intraepithelial lymphocytes; (4) marked nuclear atypia with giant/bizarre forms; and (5) abundant mitotic figures. These morphologic features were then tested on 325 ovarian tumors drawn from a population-based Greater Bay Area Cancer Registry and classified into 3 categories independent of the BRCA1 status: "Compatible with BRCA1," "Possibly compatible with BRCA1," and "Not compatible with BRCA1." All "Compatible with BRCA1" tumors were additionally investigated for presence of dominant adnexal mass, fallopian tube mucosal involvement, and uterine cornu involvement. The positive and negative predictive values for "Compatible with BRCA1" were 11/42 (26.2%) and 267/283 (94.3%), respectively, whereas combining the "Compatible with BRCA1" and "Possibly compatible with BRCA1" had positive and negative predictive values of 18/85 (21.2%) and 231/240 (96.3%), respectively. Although dominant adnexal mass and uterine cornu involvement did not add further predictive value, the likelihood of BRCA1 positivity increased to 42.9% when a tumor with "Compatible with BRCA1" histology was also associated with fallopian tube mucosal involvement. The combination of modified Nottingham grade 3 serous or undifferentiated histology, prominent intraepithelial lymphocytes, marked nuclear atypia with giant/bizarre nuclei, and high mitotic index should help to identify women for BRCA1 mutational analysis in the appropriate clinical setting. Ovarian tumors lacking this specific phenotype are unlikely to be associated with BRCA1 and should not undergo mutational analysis in the absence of other indications.
特定的形态学特征可能预测卵巢癌中 BRCA1 种系突变，但尚未得到很好的描述和独立验证。我们在一系列来自 BRCA1 突变携带者的 20 例卵巢癌中确定了与 BRCA1 突变状态相关的 5 种形态学特征：（1）改良的诺丁汉 3 级；（2）浆液性/未分化组织学；（3）上皮内淋巴细胞明显增多；（4）显著的核异型性伴巨/奇异形态；和（5）丰富的有丝分裂象。然后，我们将这些形态学特征应用于从基于人群的大湾区癌症登记处抽取的 325 例卵巢肿瘤中，并根据 BRCA1 状态将其分为 3 类：“与 BRCA1 相容”、“可能与 BRCA1 相容”和“与 BRCA1 不相容”。所有“与 BRCA1 相容”的肿瘤均进一步检查是否存在主要附件肿块、输卵管黏膜受累和子宫角受累。“与 BRCA1 相容”的阳性和阴性预测值分别为 11/42（26.2%）和 267/283（94.3%），而将“与 BRCA1 相容”和“可能与 BRCA1 相容”相结合的阳性和阴性预测值分别为 18/85（21.2%）和 231/240（96.3%）。尽管主要附件肿块和子宫角受累没有增加额外的预测价值，但当具有“与 BRCA1 相容”组织学的肿瘤也伴有输卵管黏膜受累时，BRCA1 阳性的可能性增加到 42.9%。改良的诺丁汉 3 级浆液性或未分化组织学、上皮内淋巴细胞明显增多、具有巨/奇异核的显著核异型性和高有丝分裂指数的组合应有助于在适当的临床环境下识别需要进行 BRCA1 突变分析的女性。缺乏这种特定表型的卵巢肿瘤不太可能与 BRCA1 相关，并且在没有其他指征的情况下不应进行突变分析。
