Upregulation of MICA on high-grade invasive operable breast carcinoma.
Upregulation of MICA on high-grade invasive operable breast carcinoma.
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发表时间：
2007
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通讯作者：
Z. Madjd;I. Spendlove;R. Moss;S. Bevin;S. Pinder;N. Watson;I. Ellis;L. Durrant
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作者：
Z. Madjd;I. Spendlove;R. Moss;S. Bevin;S. Pinder;N. Watson;I. Ellis;L. Durrant
MHC I类链相关基因A（云母）经常在肠上皮表面和许多上皮肿瘤中表达。云母是一种应激诱导抗原，经鉴定为通过与NKG2D受体相互作用的自然杀伤细胞激活剂。我们已经提出了一种兔多克隆抗体对合成肽，识别变性云母蛋白质印迹和福尔马林固定石蜡包埋的部分。在本研究中，该抗体用于对530例乳腺癌病例进行确定性研究，平均随访7年，以确定云母表达的预后意义。为了检测云母表达和NK浸润之间的任何关联，还分析了50个肿瘤的整个切片的CD56染色。单因素分析显示云母表达与组织学分级（P = 0.006）、淋巴结分期（P = 0.013）、诺丁汉预后指数（NPI，P = 0.002）、血管侵犯（P = 0.045）和肿瘤类型（P = 0.023）有关。云母的上调更常见于组织学等级3、预后差（NPI >5.4）的肿瘤。未证实云母高表达与NK细胞浸润的相关性，因为在整个乳房切片中存在非常少的NK细胞。我们的研究结果表明，诱导表达的云母可能是乳腺癌预后不良的指标，并表明肿瘤的环境，经历了压力，如凋亡，坏死，或缺氧。
The MHC class I chain-related gene A (MICA) is frequently expressed on the surface of intestinal epithelium and by many epithelial tumours. MICA is a stress-induced antigen which was identified as an activator of natural killer cells via interaction with the NKG2D receptor. We have raised a rabbit polyclonal antibody against a synthetic peptide that recognises denatured MICA on both Western blots and in formalin-fixed paraffin-embedded sections. In the present study this antibody was used to undertake a definitive study of 530 breast cancer cases with mean follow up of 7 years to determine the prognostic significance of MICA expression. To detect any association between MICA expression and NK infiltration, whole sections of 50 tumours were also analysed for CD56 staining. Univariate analysis showed significant relationships between MICA expression and histological grade (P = 0.006), lymph node stage (P = 0.013), Nottingham Prognostic Index (NPI, P = 0.002), the presence of vascular invasion (P = 0.045) and tumour type (P = 0.023). Upregulation of MICA was more often found in histological grade 3, poor prognosis (NPI >5.4) tumours. Association of high MICA expression with NK cell infiltration was not demonstrated, as very few NK cells were present in whole breast sections. Our results suggest that induced expression of MICA may be an indicator of poor prognosis in breast carcinoma and is indicative of a tumour environment that has undergone stresses such as apoptosis, necrosis, or hypoxia.