Lakhani S R, Jacquemier J, Sloane J P, Gusterson B A, Anderson T J, van de Vijver M J, Farid L M, Venter D, Antoniou A, Storfer-Isser A, Smyth E, Steel C M, Haites N, Scott R J, Goldgar D, Neuhausen S, Daly P A, Ormiston W, McManus R, Scherneck S, Ponder B A, Ford D, Peto J, Stoppa-Lyonnet D, Bignon Y J, Struewing J P, Spurr N K, Bishop D T, Klijn J G, Devilee P, Cornelisse C J, Lasset C, Lenoir G, Barkardottir R B, Egilsson V, Hamann U, Chang-Claude J, Sobol H, Weber B, Stratton M R, Easton D F
Department of Histopathology, University College of London Medical School, UK.
J Natl Cancer Inst. 1998 Aug 5;90(15):1138-45. doi: 10.1093/jnci/90.15.1138.
We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examination of cytologic and architectural features of these tumors.
Specimens of tumor tissue (5-microm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis. All statistical tests are two-sided.
Cancers associated with BRCA1 mutations exhibited higher mitotic counts (P = .001), a greater proportion of the tumor with a continuous pushing margin (P<.0001), and more lymphocytic infiltration (P = .002) than sporadic (i.e., control) cancers. Cancers associated with BRCA2 mutations exhibited a higher score for tubule formation (fewer tubules) (P = .0002), a higher proportion of the tumor perimeter with a continuous pushing margin (P<.0001), and a lower mitotic count (P = .003) than control cancers.
Our study has identified key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCA2 genes. This information may improve the classification of breast cancers in individuals with a family history of the disease and may ultimately aid in the clinical management of patients.
我们之前已经证明，与遗传性BRCA1和BRCA2基因突变相关的乳腺癌在组织病理学表现上彼此不同，并且这些类型中的每一种都与未选择家族史的患者中的乳腺癌（即散发性癌症）不同。我们现在对这些肿瘤的细胞学和结构特征进行了更详细的检查。
两名病理学家独立检查肿瘤组织标本（5微米厚切片），他们不知道病例或对照受试者的状态，检查是否存在细胞有丝分裂、淋巴细胞浸润、连续推挤边缘以及癌细胞实性片块；还评估了细胞核、核仁、细胞坏死和细胞边界。所得数据与先前可用的肿瘤类型和肿瘤分级信息相结合，并通过多因素分析进一步评估。所有统计检验均为双侧检验。
与散发性（即对照）癌症相比，与BRCA1突变相关的癌症表现出更高的有丝分裂计数（P = 0.001）、更大比例的肿瘤具有连续推挤边缘（P<0.0001）以及更多的淋巴细胞浸润（P = 0.002）。与BRCA2突变相关的癌症与对照癌症相比，表现出更高的小管形成评分（小管较少）（P = 0.0002）、更高比例的肿瘤周边具有连续推挤边缘（P<0.0001）以及更低的有丝分裂计数（P = 0.003）。
我们的研究确定了携带突变BRCA1和BRCA2基因的乳腺癌组织学表型的关键特征。这些信息可能会改善对有该疾病家族史个体的乳腺癌分类，并最终有助于患者的临床管理。
