乳腺导管内癌分子分型应用研究

Molecular subtyping of ductal carcinoma in situ of breast

目的采用免疫组织化学检测方法对乳腺导管内癌进行分子分型。方法收集50例乳腺导管内癌存档蜡块,用单克隆抗体CK5/6、CK8、CK18、34βE12、p63、S-100、SMA、CD10、CD117、EGFR、ER、PR和HER2进行免疫组织化学EnVision法染色,按照免疫表型分为5种类型:腺腔A型(ER+/PR+/HER2-)、腺腔B型(ER+/PR+/HER2+)、正常乳腺样型(ER-/PR-/HER2-且不表达基底/肌上皮标记及EGFR)、HER2过表达型(ER-/PR-/HER2+)和基底细胞样型(ER-/PR-/HER2-,且至少表达一种基底型角蛋白和(或)肌上皮标记物或EGFR)。结果腺腔A型16例(32%),腺腔B型19例(38%),HER2过表达型13例(26%),基底细胞样型2例(4%),无正常乳腺型。2例基底细胞样型,均表达CK5/6、CD117,例1同时表达SMA,例2表达CK8、CK18、34βE12、S-100,均为高级别导管内癌。结论乳腺导管内癌可按免疫表型进行分子分型,部分导管内癌具有与基底细胞样癌相同的免疫表型,可能是基底细胞样癌的前驱病变,其诊断依赖于免疫组化检测。

Purpose To study the molecular subtypes of ductal carcinoma in situ （DCIS）of breast by immunohistochemistry. Methods Immunohistochemistry was performed in 50 cases of DCIS, with CK5/6, CKS, CK18, 34βE12, p63, S-100, SMA, CD10, CD117, EGFR, ER, PR,and HER2 monoclonal antibodies. Five subtypes were classified according to immunophenotypes： luminal A subtype （ ER^＋/PR^＋HER2^ - ）, luminal B subtype （ ER ^＋/PR^＋/HER2 ^＋ ）, normal breast-like subtype （ ER ^-/PR ^-/HER2 ^- without expression of basal-like cytokeratins, markers of myoepithilium and EGFR）, HER2-overexpressing subtype （ER^-/PR^-/HER2^＋ ） and basal-like subtype （ER^-/PR^-/HER2^- and expression at least one basal-like cytokeratins or markers of myoepithelium or EGFR）. Results The number of luminal A case was 16 （32%）, luminal B 19 （38%） , HER2-overexpresion 13 （26%）, basal-like subtype 2 （4%）, and none of normal breast-like subtype was found. CK5/6 and CD117 were expressed in 2 cases of the basal-like subtype, in which co-expression of SMA was found in one case, and CK8, CK18, 34βE12, S-100 in the other; both of the basaMike cases were high-grade DCIS. Conclusions DCIS of breast can be classified according to immunophenotypes, and the lesions with basal-like immunophenotypes may be a precursor lesion of invasive basal-like carcinoma, which could be identified by immunohistochemistry.