Division of Pathology, School of Molecular Medical Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK.
Breast Cancer Res Treat. 2010 May;121(1):41-51. doi: 10.1007/s10549-009-0450-x. Epub 2009 Jul 10.
The basal-like or basal phenotype (BP) class of breast cancers have recently attracted attention as a poor prognostic form of breast cancer. However, BP appears to encompass biologically and clinically heterogeneous tumours, resulting in a lack of consensus definition of BP. We analysed 48,000 gene transcripts in 132 invasive breast carcinomas to identify two novel genes (OATP2 and FABP7) significantly associated with BP [defined by cytokeratin (CK)5/6 and/or CK14 positivity]. Using a series of invasive breast carcinoma cases (n = 899), prepared as tissue microarrays, we assessed OATP2 and FABP7 protein expression using immunohistochemistry to investigate associations with clinicopathological variables, patients' outcome and ability to refine BP classification. A total of 7.9 and 15.6% cases were OATP2 and FABP7 positive, respectively. OATP2 was associated with tumours of high histological grade (p < 0.01), ER and PgR negativity (p < 0.01) and shorter breast cancer-specific survival (p = 0.04). FABP7 expression was associated with lower lymph node stage (p < 0.01), ER and PgR negativity (p < 0.01). BP tumours which were FABP7 positive had a significantly longer BCSS (p = 0.05) and disease-free survival (p = 0.01) compared with FABP7 negative basal tumours (p < 0.01). OATP2 positive tumours were associated with adverse survival and increased risk of early recurrence. This study confirms the biological and clinical heterogeneity of the BP in breast cancer. We have identified a novel subgroup of basal tumours showing FABP7 expression that have significantly better clinical outcome. Further studies analysing the role of FABP7 are therefore warranted.
基底样或基底表型（BP）类乳腺癌最近引起了人们的关注，因为它是一种预后不良的乳腺癌形式。然而，BP 似乎包含了生物学和临床上异质的肿瘤，导致 BP 缺乏共识定义。我们分析了 132 例浸润性乳腺癌的 48000 个基因转录本，以鉴定两个与 BP 显著相关的新基因（OATP2 和 FABP7）[由细胞角蛋白（CK）5/6 和/或 CK14 阳性定义]。使用一系列作为组织微阵列制备的浸润性乳腺癌病例（n = 899），我们使用免疫组织化学评估 OATP2 和 FABP7 蛋白表达，以研究与临床病理变量、患者结局和改善 BP 分类的能力的关联。OATP2 和 FABP7 阳性病例分别占 7.9%和 15.6%。OATP2 与高组织学分级的肿瘤相关（p < 0.01）、ER 和 PgR 阴性（p < 0.01）以及乳腺癌特异性生存率较短（p = 0.04）。FABP7 表达与较低的淋巴结分期相关（p < 0.01）、ER 和 PgR 阴性（p < 0.01）。与 FABP7 阴性的基底肿瘤相比，FABP7 阳性的 BP 肿瘤的乳腺癌特异性生存率（p = 0.05）和无病生存率（p = 0.01）显著更长。OATP2 阳性肿瘤与不良生存和早期复发风险增加相关。这项研究证实了乳腺癌中 BP 的生物学和临床异质性。我们已经确定了一个新的基底肿瘤亚组，显示出 FABP7 表达，具有显著更好的临床结局。因此，进一步研究分析 FABP7 的作用是有必要的。
