Rakha Emad A, Boyce Richard W G, Abd El-Rehim Dalia, Kurien Thomas, Green Andrew R, Paish Emma C, Robertson John F R, Ellis Ian O
Department of Histopathology, The Breast Unit, Nottingham City Hospital, University of Nottingham, Nottingham, UK.
Mod Pathol. 2005 Oct;18(10):1295-304. doi: 10.1038/modpathol.3800445.
Mucins are a large family of glycoproteins expressed by many epithelial cells and their malignant counterparts. Much interest has been focused on expression of its members in breast cancer because of their potential role as prognostic indicators and their involvement in cancer therapy. We have examined 1447 cases of invasive breast carcinoma with a long-term follow-up, using tissue microarray (TMA) technology and immunohistochemistry to evaluate the expression profiles of several mucins (MUC1, MUC2, MUC3, MUC4, MUC5AC and MUC6) and to assess their prognostic value. We detected MUC1 expression in 91% of tumours. MUC1 overexpression was associated with a lower grade, smaller tumour size, a higher oestrogen receptor (ER)-positive phenotype and absence of both regional recurrence and distance metastasis. The subcellular localization but not the level of expression had a prognostic value in predicting outcome. The aberrant cytoplasmic and membranous localization of MUC1 was associated with poor outcome compared with apical localization, which is the normal physiological site of expression. MUC2 expression was noticed in only 8.3% of all cases and was restricted to the cytoplasm of the tumour cells. An inverse trend was identified between MUC2 expression and lymph node stage and vascular invasion status. On excluding cases of mucinous carcinoma from the analysis, the inverse association with vascular invasion was still defined and in addition an inverse association with ER status emerged. MUC3 expression was detected in 91% of cases and its expression was associated with increased local recurrence, and lymph node stage. The membranous expression of MUC3 was found to be a potentially poor prognostic feature, with higher grade and poorer Nottingham Prognostic Index (NPI), and negative ER expression. MUC4, MUC5AC and MUC6 were expressed in 95, 37 and 20% of cases, respectively. Apart from an association between MUC4 expression and tumour grade and between MUC6 and ER-negative tumours, no other associations with any clinicopathological variables were found. Apart from the higher expression of MUC2 and MUC6 in mucinous carcinomas, no association was found between the expression of different mucins and tumour type. No association between the level of expression of any of the studied mucins and patient outcomes has been identified. In conclusion, most breast carcinomas express MUC1, MUC3 and MUC4. Among the various mucins expressed in breast cancer, MUC1 and MUC3 are potential prognostic indicators, MUC1 having the strongest relationship with patient outcome.
黏蛋白是由许多上皮细胞及其恶性对应细胞表达的一大类糖蛋白。由于其作为预后指标的潜在作用以及在癌症治疗中的参与,其成员在乳腺癌中的表达备受关注。我们使用组织微阵列(TMA)技术和免疫组织化学对1447例浸润性乳腺癌进行了长期随访,以评估几种黏蛋白(MUC1、MUC2、MUC3、MUC4、MUC5AC和MUC6)的表达谱并评估其预后价值。我们在91%的肿瘤中检测到MUC1表达。MUC1过表达与较低分级、较小肿瘤大小、较高雌激素受体(ER)阳性表型以及无区域复发和远处转移相关。MUC1的亚细胞定位而非表达水平在预测预后方面具有预后价值。与正常生理表达部位顶端定位相比,MUC1异常的细胞质和膜定位与不良预后相关。仅在所有病例的8.3%中发现MUC2表达,且仅限于肿瘤细胞的细胞质。在MUC2表达与淋巴结分期和血管侵犯状态之间发现了相反的趋势。在分析中排除黏液癌病例后,与血管侵犯的负相关仍然存在,此外还出现了与ER状态的负相关。在91%的病例中检测到MUC3表达,其表达与局部复发增加和淋巴结分期相关。发现MUC3的膜表达是一个潜在的不良预后特征,具有更高分级和更差的诺丁汉预后指数(NPI)以及ER阴性表达。MUC4、MUC5AC和MUC6分别在95%、37%和20%的病例中表达。除了MUC4表达与肿瘤分级之间以及MUC6与ER阴性肿瘤之间的关联外,未发现与任何临床病理变量的其他关联。除了黏液癌中MUC2和MUC6的较高表达外,未发现不同黏蛋白的表达与肿瘤类型之间的关联。未发现任何研究的黏蛋白表达水平与患者预后之间的关联。总之,大多数乳腺癌表达MUC1、MUC3和MUC4。在乳腺癌中表达的各种黏蛋白中,MUC1和MUC3是潜在的预后指标,MUC1与患者预后的关系最为密切。