Bohn Olga L, Fuertes-Camilo Mariana, Navarro Leticia, Saldivar Jesus, Sanchez-Sosa Sergio
Department of Pathology, MetroHealth Medical Center-Case Western Reserve University, Cleveland, OH 44109, USA.
Int J Clin Exp Pathol. 2010 Jun 30;3(6):600-7.
BLBC represents a distinctive group of invasive breast carcinomas with specific genotype and immunoprofile. BLBC is usually defined by gene expression profiling and is currently associated with poor outcome. BLBCs are estrogen receptor (ER) negative, progesterone receptor (PgR) negative, HER2 negative, and usually show a variable expression of basal cytokeratins (CKs), EGFR and CD117. p16(INK4a) is a tumor suppressor protein, encoded by the CDKN2A gene, which regulates cell cycle. The reported association of abnormalities in the p16/Rb pathway with increased risk of malignancy prompted us to determine the expression of p16(INK4a) in a group of BLBC; the results were compared with a group of high-grade invasive carcinoma (HG-IC) of breast. Tissue microarrays (TMA) were constructed in triplicate including 18 BLBC and 18 HG-IC. All BLBC cases were ER-/PgR-/HER2-. Seventeen (94%) BLBC were CK 5/6+/CK 14+; 14 (78%) BLCB showed EGFR expression and 13 (72%) were CD117 positive. BLBCs showed a strong positive reaction with p16(INK4a) antibody in 16 of 18 (89%) cases. Although the significance of p16(INK4a) expression in breast cancer is not fully understood, we have shown that p16(INK4a) is strongly expressed in breast cancers with basal-like phenotype. Since it is known that p16(INK4a) is associated with aggressive behavior in human carcinomas, these data suggest that p16(INK4a) play a role in the poor prognosis of BLBC.
基底样乳腺癌(BLBC)是一组具有独特基因型和免疫表型的浸润性乳腺癌。BLBC通常通过基因表达谱来定义,目前与预后不良相关。BLBC雌激素受体(ER)阴性、孕激素受体(PgR)阴性、HER2阴性,通常显示基底细胞角蛋白(CKs)、表皮生长因子受体(EGFR)和CD117表达各异。p16(INK4a)是一种肿瘤抑制蛋白,由CDKN2A基因编码,调控细胞周期。p16/Rb通路异常与恶性肿瘤风险增加之间的报道关联促使我们测定一组BLBC中p16(INK4a)的表达;结果与一组乳腺高级别浸润性癌(HG-IC)进行比较。构建了包含18例BLBC和18例HG-IC的组织芯片(TMA),一式三份。所有BLBC病例均为ER-/PgR-/HER2-。17例(94%)BLBC为CK 5/6+/CK 14+;14例(78%)BLCB显示EGFR表达,13例(72%)CD117阳性。18例BLBC中有16例(89%)与p16(INK4a)抗体呈强阳性反应。虽然p16(INK4a)在乳腺癌中表达的意义尚未完全明确,但我们已表明p16(INK4a)在具有基底样表型的乳腺癌中强烈表达。由于已知p16(INK4a)与人癌中的侵袭性行为相关,这些数据提示p16(INK4a)在BLBC的不良预后中起作用。