Livasy Chad A, Karaca Gamze, Nanda Rita, Tretiakova Maria S, Olopade Olufunmilayo I, Moore Dominic T, Perou Charles M
Department of Pathology and Lab Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA.
Mod Pathol. 2006 Feb;19(2):264-71. doi: 10.1038/modpathol.3800528.
Microarray profiling of invasive breast carcinomas has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpressing, and basal-like) that are associated with different clinical outcomes. The basal-like subtype is associated with poor clinical outcomes and is the subtype observed in BRCA1-related breast cancers. The aim of this study was to characterize the histologic and immunophenotypic properties of breast basal-like carcinomas that were first positively identified using DNA microarray analysis. Detailed histologic review was performed on 56 tumors with known microarray profiles (23 basal-like, 23 luminal, and 12 HER2+). Immunohistochemistry for estrogen receptor (ER), HER2, EGFR, smooth muscle actin (SMA), p63, CD10, cytokeratin 5/6, cytokeratin 8/18, and vimentin was performed on 18 basal-like, 16 luminal, and 12 HER2+ tumors. The basal-like tumors were grade 3 ductal/NOS (21/23) or metaplastic (2/23) carcinomas that frequently showed geographic necrosis (17/23), a pushing border of invasion (14/23), and a stromal lymphocytic response (13/23). Most basal-like tumors showed immunoreactivity for vimentin (17/18), luminal cytokeratin 8/18 (15/18), EGFR (13/18), and cytokeratin 5/6 (11/18), while positivity for the myoepithelial markers SMA (4/18), p63 (4/18) and CD10 (2/18) was infrequent. All basal-like tumors tested were ER- and HER2-. Morphologic features significantly associated with the basal-like subtype included markedly elevated mitotic count (P<0.0001), geographic tumor necrosis (P=0.0003), pushing margin of invasion (P=0.0001), and stromal lymphocytic response (P=0.01). The most consistent immunophenotype seen in the basal-like tumors was negativity for ER and HER2, and positivity for vimentin, EGFR, cytokeratin 8/18, and cytokeratin 5/6. The infrequent expression of myoepithelial markers in basal-like carcinomas does not support a direct myoepithelial cell derivation of these tumors. These findings should further assist in the identification of basal-like carcinomas in clinical specimens, facilitating treatment and epidemiologic studies of this tumor subtype.
浸润性乳腺癌的基因芯片分析已确定了五种不同的肿瘤亚型(腔面A型、腔面B型、正常乳腺样型、HER2过表达型和基底样型),这些亚型与不同的临床结局相关。基底样亚型与不良临床结局相关,是在BRCA1相关乳腺癌中观察到的亚型。本研究的目的是描述首次通过DNA微阵列分析阳性鉴定的乳腺基底样癌的组织学和免疫表型特征。对56例具有已知基因芯片图谱的肿瘤(23例基底样型、23例腔面型和12例HER2阳性型)进行了详细的组织学检查。对18例基底样型、16例腔面型和12例HER2阳性型肿瘤进行了雌激素受体(ER)、HER2、表皮生长因子受体(EGFR)、平滑肌肌动蛋白(SMA)、p63、CD10、细胞角蛋白5/6、细胞角蛋白8/18和波形蛋白的免疫组织化学检测。基底样肿瘤为3级导管癌/非特殊类型(21/23)或化生癌(2/23),常表现为地图状坏死(17/23)、推挤性浸润边缘(14/23)和间质淋巴细胞反应(13/23)。大多数基底样肿瘤对波形蛋白(17/18)、腔面细胞角蛋白8/18(15/18)、EGFR(13/18)和细胞角蛋白5/6(11/18)呈免疫反应,而肌上皮标志物SMA(4/18)、p63(4/18)和CD10(2/18)的阳性率较低。所有检测的基底样肿瘤均为ER和HER2阴性。与基底样亚型显著相关的形态学特征包括有丝分裂计数明显升高(P<0.0001)、地图状肿瘤坏死(P=0.0003)、推挤性浸润边缘(P=0.0001)和间质淋巴细胞反应(P=0.01)。在基底样肿瘤中最一致的免疫表型是ER和HER2阴性,波形蛋白、EGFR、细胞角蛋白8/18和细胞角蛋白5/6阳性。基底样癌中肌上皮标志物的低表达不支持这些肿瘤直接来源于肌上皮细胞。这些发现应进一步有助于临床标本中基底样癌的识别,促进该肿瘤亚型的治疗和流行病学研究。