Gray Sarah E, Kay Elaine W, Leader Mary, Mabruk Mohamed J E M F
Molecular Oncology Laboratory, Pathology Department, Royal College of Surgeons in Ireland (RCSI) and the Beaumont Hospital, Dublin, Ireland.
Mol Diagn Ther. 2006;10(5):327-34. doi: 10.1007/BF03256208.
Microsatellite instability (MSI) is a phenotypic characteristic of tumors with biallelic inactivation of mismatch repair genes, such as MSH2 or MLH1, and contributes to malignant transformation.
The aim of this study was to examine the prevalence of MSI in cutaneous squamous cell carcinoma (SCC) using a PCR and fluorescent-based detection system. These methods of analysis offer several advantages over the use of silver staining and autoradiographic techniques. We also aimed to determine if MSI status correlated with expression of the MSH2 and MLH1 mismatch repair proteins in these cutaneous SCC samples.
The MSI status of 22 histologically confirmed invasive cutaneous SCC samples were analyzed at five microsatellite markers (the National Cancer Institute's Bethesda panel of two mononucleotide and three dinucleotide markers) using a PCR and fluorescent-based detection system. Immunohistochemical analysis of MSH2 and MLH1 protein expression was also carried out on the SCC samples.
Only one case of cutaneous SCC displayed MSI. This was found at just one of five markers, and thus was low frequency MSI. All 22 cutaneous SCC cases strongly expressed MSH2 protein. Eighteen (82%) of the cutaneous SCC cases showed moderate to strong expression of MLH1 protein. The remaining four cases of cutaneous SCC were negative for MLH1 protein. Therefore, the majority of the SCC patients analyzed showed a correlation between absence of MSI and expression of MSH2 and MLH1 proteins.
MSI is uncommon in cutaneous SCC. In addition, MSH2 was strongly expressed in all SCC samples analyzed and appeared to be upregulated when compared with the corresponding normal tissue. MLH1 protein was not detected in 4 of 22 SCC cases, although it was expressed in the corresponding normal tissue, suggesting that inactivation of MLH1 may be a late event in a subset of invasive SCC cases.
微卫星不稳定性（MSI）是错配修复基因双等位基因失活的肿瘤的一种表型特征，如MSH2或MLH1，并且促成恶性转化。
本研究的目的是使用基于聚合酶链反应（PCR）和荧光的检测系统来检测皮肤鳞状细胞癌（SCC）中MSI的发生率。这些分析方法比使用银染和放射自显影技术具有多个优势。我们还旨在确定在这些皮肤SCC样本中MSI状态是否与MSH2和MLH1错配修复蛋白的表达相关。
使用基于PCR和荧光的检测系统，在五个微卫星标记（美国国立癌症研究所贝塞斯达小组的两个单核苷酸和三个二核苷酸标记）处分析22个经组织学确诊的浸润性皮肤SCC样本的MSI状态。还对SCC样本进行了MSH2和MLH1蛋白表达的免疫组织化学分析。
仅1例皮肤SCC显示MSI。这仅在五个标记之一处被发现，因此是低频MSI。所有22例皮肤SCC病例均强烈表达MSH2蛋白。18例（82%）皮肤SCC病例显示MLH1蛋白中度至强表达。其余4例皮肤SCC病例MLH1蛋白为阴性。因此，大多数分析的SCC患者显示MSI缺失与MSH2和MLH1蛋白表达之间存在相关性。
MSI在皮肤SCC中不常见。此外，在所有分析的SCC样本中MSH2均强烈表达，并且与相应的正常组织相比似乎上调。22例SCC病例中有4例未检测到MLH1蛋白，尽管它在相应的正常组织中表达，这表明MLH1失活可能是一部分浸润性SCC病例中的晚期事件。
