Saetta Angelica A, Aroni Kiriaki, Stamatelli Angeliki, Lazaris Andreas C, Patsouris Efstratios
Department of Pathology, Medical School, The National and Kapodistrian University of Athens, 75 Mikras Asias Str., Goudi, 115 27 Athens, Greece.
Arch Dermatol Res. 2005 Sep;297(3):99-107. doi: 10.1007/s00403-005-0580-x. Epub 2005 Sep 29.
Microsatellite instability (MSI) constitutes an alternative-to the chromosomal instability-pathway of carcinogenesis for certain tumour types with prognostic and therapeutic significance for the respective patients. MSI is caused by mutations in mismatch repair (MMR) genes, mainly hMLH1, hMSH2, leading to a defective MMR system. The role of MSI in basal cell carcinoma (BCC) has not been clearly delineated yet. p53 gene as a target for ultraviolet radiation-induced mutations may enhance genomic instability in BCC, with loss of its function. Our aim was to investigate the involvement of MSI and expression of hMLH1 and hMSH2 in parallel with P53 protein accumulation in the pathogenesis of BCC and its possible correlation to the clinicopathological features of the patients. The presence of MSI was investigated in 76 BCCs using mononucleotide microsatellite markers, BAT-25, BAT-26 and TGF-beta receptor type II (TGF-beta-RII). Additionally, 3 dinucleotide markers were analysed in 20 cases in which matched normal tissue was available. The expression of hMLH1, hMSH2 and P53 proteins was evaluated by immunohistochemical analysis. Alterations of the BAT-26 marker were observed in one fibroepithelioma of Pincus, one nodular and one multifocal superficial BCC. A keratotic BCC showed an altered BAT-25 locus. Two samples, a multifocal superficial and a nodular BCC, displayed MSI at two markers (BAT-25 and BAT-26; and BAT-25 and TGF-beta-RII, respectively). Three more cases, a metatypical, a multifocal superficial and a signet ring BCC exhibited frameshift mutations in the TGF-beta-RII. No sample showed length alterations at the dinucleotide markers examined. hMLH1 and hMSH2 protein immunohistochemical expression was scored positive in 46 and 49 out of 52 cases respectively. P53 accumulation was observed in 27 out of 56 samples. Correlation of the molecular and immunohistochemical findings with the clinicopathological parameters produced no statistically significant results. No correlation between MSI and hMLH1, hMSH2 or P53 protein expression was determined. MSI appears to play a minor role in the pathogenesis of BCCs being present only in a small subset of such tumours.
微卫星不稳定性（MSI）是某些肿瘤类型致癌的一种替代染色体不稳定性的途径，对相应患者具有预后和治疗意义。MSI由错配修复（MMR）基因的突变引起，主要是hMLH1、hMSH2，导致MMR系统缺陷。MSI在基底细胞癌（BCC）中的作用尚未明确界定。p53基因作为紫外线辐射诱导突变的靶点，可能会增强BCC中的基因组不稳定性，并导致其功能丧失。我们的目的是研究MSI以及hMLH1和hMSH2的表达与P53蛋白积累在BCC发病机制中的参与情况，及其与患者临床病理特征的可能相关性。使用单核苷酸微卫星标记BAT-25、BAT-26和II型转化生长因子-β受体（TGF-β-RII）在76例BCC中检测MSI的存在。此外，在20例有匹配正常组织的病例中分析了3个二核苷酸标记。通过免疫组织化学分析评估hMLH1、hMSH2和P53蛋白的表达。在1例平卡斯纤维上皮瘤、1例结节性和1例多灶性浅表BCC中观察到BAT-26标记的改变。1例角化性BCC显示BAT-25位点改变。2个样本，1例多灶性浅表BCC和1例结节性BCC，分别在两个标记（BAT-25和BAT-26；BAT-25和TGF-β-RII）处显示MSI。另外3例，1例异型、1例多灶性浅表和1例印戒样BCC在TGF-β-RII中表现出移码突变。在所检测的二核苷酸标记处，没有样本显示长度改变。在52例病例中，分别有46例和49例hMLH1和hMSH2蛋白免疫组织化学表达呈阳性。在56个样本中有27个观察到P53积累。分子和免疫组织化学结果与临床病理参数的相关性未产生统计学上的显著结果。未确定MSI与hMLH1、hMSH2或P53蛋白表达之间的相关性。MSI似乎在BCC的发病机制中起次要作用，仅存在于此类肿瘤的一小部分中。
