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免疫组织化学分析在鼻腔鼻窦腺癌中的黏蛋白表达谱。

Immunohistochemical profiling of mucins in sinonasal adenocarcinomas.

机构信息

Department of Health Sciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.

Otolaryngology, Head and Neck Surgery, Azienda Ospedaliera Universitaria "Careggi", Largo Brambilla 3, 50134, Florence, Italy.

出版信息

Pathol Res Pract. 2019 Jul;215(7):152439. doi: 10.1016/j.prp.2019.152439. Epub 2019 May 4.

Abstract

In this study we investigated the expression of mucins (MUC1, MUC2, MUC4, MUC5AC and MUC6) in a series of 66 sinonasal adenocarcinomas, in order to establish their distribution and the possible correlation with clinicopathological and prognostic parameters. The series included 51 intestinal type adenocarcinomas, 4 non-intestinal type adenocarcinomas, and 11 salivary gland type carcinomas. The immunohistochemical analysis was conducted on a tissue microarray obtained from formalin fixed-paraffin embedded tumor tissue samples. Thirty-nine adenocarcinomas (59.1%) resulted positive for MUC1, 21 (41.2%) for MUC2, 47 (71.2%) for MUC4, and 16 (24.2%) for MUC5AC, while MUC6 was negative in all cases tested. MUC1 was significantly more expressed in ITACs than in non-ITACs (70% vs 20%, p = 0.0007) while MUC2 was expressed only in ITACs (p = 0.0015) with a clear prevalence in the mucinous subtype (p < 0.0001). Conversely, MUC4 and MUC5AC were similarly expressed in the sinonasal adenocarcinoma subtypes tested. High expression of MUC 1 was related to a significantly shorter overall survival, both in the whole series (p = 0.04), while adenocarcinomas positive for MUC 2 tended to have a worse overall survival (p = 0.07). In addition, MUC2 expression was higher in ITACs with distant metastasis, being expressed in 4 out of 5 cases (p = 0.015). We conclude that sinonasal adenocarcinomas have a characteristic expression of different mucin types, with significant clinicopathologic correlations. In view of the extensive involvement of mucins in different aspects of tumor growth and their emerging role as possible therapeutic targets, our study suggests that these factors could be considered clinically relevant biomarkers and attractive targets for new treatments in sinonasal adenocarcinomas.

摘要

在这项研究中,我们研究了黏蛋白(MUC1、MUC2、MUC4、MUC5AC 和 MUC6)在 66 例鼻窦腺癌中的表达情况,以确定其分布以及与临床病理和预后参数的可能相关性。该系列包括 51 例肠型腺癌、4 例非肠型腺癌和 11 例唾液腺型癌。免疫组织化学分析是在从福尔马林固定石蜡包埋的肿瘤组织样本获得的组织微阵列上进行的。39 例腺癌(59.1%)MUC1 阳性,21 例(41.2%)MUC2 阳性,47 例(71.2%)MUC4 阳性,16 例(24.2%)MUC5AC 阳性,而所有测试的病例均为 MUC6 阴性。MUC1 在 ITACs 中的表达明显高于非-ITACs(70%对 20%,p=0.0007),而 MUC2 仅在 ITACs 中表达(p=0.0015),且在黏液亚型中具有明显优势(p<0.0001)。相反,MUC4 和 MUC5AC 在检测到的鼻窦腺癌亚型中表达相似。MUC1 的高表达与总生存率显著相关,无论是在整个系列中(p=0.04),还是在 MUC2 阳性的腺癌中(p=0.07),总生存率均较差。此外,在远处转移的 ITAC 中,MUC2 的表达更高,5 例中有 4 例(p=0.015)。我们得出结论,鼻窦腺癌具有不同黏蛋白类型的特征性表达,与显著的临床病理相关性。鉴于黏蛋白在肿瘤生长的各个方面的广泛参与,以及它们作为可能的治疗靶点的新兴作用,我们的研究表明,这些因素可能被认为是临床相关的生物标志物,并为鼻窦腺癌的新治疗方法提供有吸引力的靶点。

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