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研究唾液腺黏液表皮样癌和腺样囊性癌中 FHIT 和 WWOX 的表达。

Study of FHIT and WWOX expression in mucoepidermoid carcinoma and adenoid cystic carcinoma of salivary gland.

机构信息

Hacettepe University, Faculty of Medicine, Department of Pathology, Ankara, Turkey.

出版信息

Oral Oncol. 2010 Mar;46(3):195-9. doi: 10.1016/j.oraloncology.2009.12.003. Epub 2010 Jan 8.

Abstract

Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are salivary gland neoplasms with divergent morphological features and clinical behavior. ACC is a basaloid tumor whereas MEC is a glandular epithelial neoplasm. FHIT and WWOX are tumor suppressor genes that encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3, respectively. In previous studies, we have shown concordant loss of Fhit and Wwox expression in breast cancer, with significantly more frequent loss in cancers of basal-like phenotype. To determine if there is a similar association in salivary gland neoplasms, we designed a study of MEC and ACC of salivary gland on tissue microarrays (TMA). TMAs were constructed from 25 MEC and 19 ACC of salivary gland. Fhit and Wwox protein expression was assessed by immunohistochemical staining of cores on TMAs. Correlations among immunohistochemical markers and histological type were determined by statistical analyses. Significantly reduced Fhit and Wwox expression was observed in ACC (p=0.002 and p<0.001, respectively). The results suggest that, as for breast cancer, loss of Fhit and Wwox expression might have a role in the pathogenesis of basaloid differentiation in salivary gland neoplasms; alternatively, differences in chromatin structure at chromosome fragile regions might make fragile genes more accessible to DNA damage and rearrangement early during preneoplastic stages of basaloid cancers. Studies of basaloid tumors of other organ systems may show similar results and these findings may have implications for treatment modalities designed for basal-like tumors.

摘要

黏液表皮样癌(MEC)和腺样囊性癌(ACC)是具有不同形态特征和临床行为的唾液腺肿瘤。ACC 是基底样肿瘤,而 MEC 是腺上皮肿瘤。FHIT 和 WWOX 是肿瘤抑制基因,分别包含染色体 3p14.2 和 16q23.3 上的 FRA3B 和 FRA16D 脆性位点。在之前的研究中,我们已经证明了 FHIT 和 WWOX 在乳腺癌中的表达缺失具有一致性,并且在基底样表型的癌症中更为频繁。为了确定在唾液腺肿瘤中是否存在类似的关联,我们设计了一项关于唾液腺 MEC 和 ACC 的组织微阵列(TMA)研究。从 25 例唾液腺 MEC 和 19 例 ACC 中构建 TMA。通过 TMA 上的核心免疫组织化学染色评估 Fhit 和 Wwox 蛋白表达。通过统计分析确定免疫组织化学标志物与组织学类型之间的相关性。在 ACC 中观察到明显减少的 Fhit 和 Wwox 表达(p=0.002 和 p<0.001)。结果表明,与乳腺癌一样,Fhit 和 Wwox 表达的缺失可能在唾液腺肿瘤中基底样分化的发病机制中起作用;或者,染色体脆性区域的染色质结构的差异可能使脆性基因在基底样癌的肿瘤前阶段更容易受到 DNA 损伤和重排的影响。其他器官系统的基底样肿瘤的研究可能会显示出类似的结果,这些发现可能对为基底样肿瘤设计的治疗方式具有重要意义。

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