Ductal carcinoma in situ with basal-like phenotype:: a possible precursor to invasive basal-like breast cancer
Ductal carcinoma in situ with basal-like phenotype:: a possible precursor to invasive basal-like breast cancer
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DOI：
10.1038/modpathol.3800570
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发表时间：
2006-05-01
期刊：
影响因子：
7.5
通讯作者：
Collins, LC
中科院分区：
文献类型：
--
作者：
Bryan, BB;Schnitt, SJ;Collins, LC
最近在基因表达谱研究中发现基底样癌是浸润性乳腺癌的一种亚型。这些病变为雌激素受体 (ER) 阴性、孕激素受体 (PR) 阴性和 HER2 阴性（三阴性），通常表达基底细胞角蛋白、表皮生长因子受体 (EGFR) 和/或 c-kit。作为分化差的浸润性导管癌，它们可能具有具有相似细胞学和免疫表型特征的导管原位癌（DCIS）前体。然而，之前尚未评估过具有与侵袭性基底样癌类似的免疫表型的 DCIS 病变的频率甚至是否存在。我们使用针对 ER、PR、HER2、三种基底细胞角蛋白、EGFR 和 c-kit 的抗体研究了 66 例高核级 DCIS 病例，以确定三阴性表型的频率，并确定三阴性表型与基底细胞角蛋白和其他侵袭性基底样癌特征性表达的生物标志物的表达之间的关系。 4例（6%）表现出三阴性表型；其余病例显示 ER、PR 和 HER2 表达的其他组合（非三阴性）。所有四个三阴性病变均表达基底细胞角蛋白、EGFR 或两者，但 51 个非三阴性病例中仅 21 个 (42%) 表达 (P = 0.04)。我们的结论是，一小部分高级别导管原位癌表现出 ER 阴性/PR 阴性/HER2 阴性（三阴性）表型，并且这些病变比非三阴性高级别 DCIS 更常见地显示基底细胞角蛋白和/或 EGFR 的表达。鉴于浸润性乳腺癌通常与原位导管癌具有相同的免疫表型特征，我们的研究结果提出了这样一种可能性：我们确定的三阴性、基底细胞角蛋白和/或 EGFR 阳性 DCIS 病变代表了浸润性基底样癌的前驱病变。
Basal-like carcinomas have recently been identified in gene expression profiling studies as a subtype of invasive breast cancer. These lesions are estrogen receptor ( ER)-negative, progesterone receptor ( PR)negative, and HER2-negative (triple negative), and typically express basal cytokeratins, epidermal growth factor receptor ( EGFR), and/or c-kit. As poorly differentiated invasive ductal carcinomas, they presumably have a ductal carcinoma in situ ( DCIS) precursor with similar cytologic and immunophenotypic features. However, the frequency and even the existence of a DCIS lesion with an immunophenotype analogous to that of invasive basal-like carcinomas have not been previously evaluated. We studied 66 cases of high nuclear grade DCIS using antibodies to ER, PR, HER2, three basal cytokeratins, EGFR, and c-kit to determine the frequency of the triple negative phenotype, and to determine the relationship between the triple negative phenotype and expression of basal cytokeratins and other biomarkers characteristically expressed by invasive basal-like carcinomas. Four cases (6%) exhibited the triple negative phenotype; the remaining cases showed other combinations of ER, PR, and HER2 expression (nontriple negative). Basal cytokeratins, EGFR, or both were expressed by all four triple negative lesions, but by only 21 of 51 (42%) nontriple negative cases (P = 0.04). We conclude that a small proportion of high-grade ductal carcinomas in situ exhibit an ER-negative/PR-negative/ HER2-negative ( triple negative) phenotype, and these lesions more commonly show expression of basal cytokeratins and/or EGFR than nontriple negative high-grade DCIS. Given that invasive breast cancers typically share immunophenotypic features with the ductal carcinoma in situ from which they arise, our findings raise the possibility that the triple-negative, basal cytokeratin and/or EGFR- positive DCIS lesions we identified represent a precursor lesion to invasive basal-like carcinomas.