Most basal-like breast carcinomas demonstrate the same Rb-/p16+ immunophenotype as the HPV-related poorly differentiated squamous cell carcinomas which they resemble morphologically.
Most basal-like breast carcinomas demonstrate the same Rb-/p16+ immunophenotype as the HPV-related poorly differentiated squamous cell carcinomas which they resemble morphologically.
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DOI：
10.1097/pas.0b013e31817f9790
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Argani P
中科院分区：
文献类型：
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作者：
Subhawong AP;Subhawong T;Nassar H;Kouprina N;Begum S;Vang R;Westra WH;Argani P
乳腺基底细胞样癌（BLC）与低分化高危型人乳头状瘤病毒（HPV）相关的口咽部、阴茎和外阴鳞状细胞癌有共同的形态学特征。由于HPV E7蛋白使视网膜母细胞瘤（Rb）蛋白失活，因此弥漫性p16表达是这些高危HPV相关癌的替代标志物。HPV E6蛋白也使p53失活，进一步损害G1-S细胞周期检查点。乳腺BLC的Rb/p16/p53免疫组化谱尚未得到很好的表征。包含71个乳腺浸润性导管癌（IDC）的组织微阵列进行p16，Rb，p53和Ki-67的免疫标记。这些病例包括4组不同的IDC，其替代免疫组织化学谱对应于基因表达谱定义的类别（17例管腔A，7例管腔B，14例HER-2+和21例BLC），沿着12例不可分类的三阴性癌（UTNC）。71例IDC中有25例为Rb阴性/p16弥漫阳性（Rb −/p16+）。其中BLC 15/21例，UTNC 9/12例，HER-2阳性1/14例，管腔A型17例，管腔B型7例，两者比较差异有显著性（P < 0.01）。6例Rb − /p16+ IDC也有明显的导管原位癌成分。这6例中有4例导管原位癌表现出与相关IDC相同的Rb − /p16+表型。BLC和UTNC的Ki-67指数在5组中最高，即使在分级匹配时也是如此。Rb − /p16+表型和Rb − /p16+/p53过表达表型与BLC组内增殖增加相关。总之，BLC和UTNC，而不是HER-2，管腔A或管腔B癌，经常表现出Rb − /p16+表型，类似于HPV相关的鳞状细胞癌，BLC形态学相似。该子集可以表示比当前定义的BLC更同质的组。
Basal-like carcinomas (BLCs) of the breast share discriminatory morphologic features with poorly differentiated high-risk human papilloma virus (HPV)-related squamous cell carcinomas of the oropharynx, penis, and vulva. Because HPV E7 protein inactivates the retinoblastoma (Rb) protein, diffuse p16 expression is a surrogate marker for these high-risk HPV-related carcinomas. HPV E6 protein also inactivates p53, further compromising the G1-S cell cycle checkpoint. The Rb/p16/p53 immunohistochemical profile of BLC of the breast has not been well characterized. Tissue microarrays containing 71 invasive ductal carcinomas (IDCs) of the breast were immunolabeled for p16, Rb, p53, and Ki-67. The cases included 4 distinct groups of IDCs having surrogate immunohistochemical profiles corresponding to categories defined by gene expression profiling (17 luminal A, 7 luminal B, 14 HER-2+, and 21 BLC), along with 12 unclassifiable triple negative carcinomas (UTNCs). Twenty-five of the 71 IDC were Rb negative/p16 diffuse positive (Rb −/p16+). These included 15 of 21 BLC and 9 of 12 UTNC, but only 1 of 14 HER-2 positive cases and none of the 17 luminal A or 7 luminal B cases (P < 0.01, BLC or UTNC vs. others). Six of the Rb − /p16+ IDC also had a significant ductal carcinoma in situ component. The ductal carcinoma in situ in 4 of these 6 cases showed the same Rb − /p16+ phenotype as the associated IDC. BLC and UTNC had the highest Ki-67 indices of the 5 groups, even when matched for grade. The Rb − /p16+ phenotype and the Rb − /p16+/p53 overexpressing phenotype correlated with increased proliferation within the BLC group. In conclusion, BLC and UTNC, but not HER-2, luminal A, or luminal B carcinomas, frequently demonstrate an Rb − /p16+ phenotype, similar to the HPV-related squamous cell carcinomas that BLC resemble morphologically. This subset may represent a more homogenous group than BLC as defined currently.