Miturski Roman, Bogusiewicz Michal, Tarkowski Rafal, Ciotta Carmella, Bignami Margherita, Burnouf Dominique, Jakowicki Jerzy A
Second Department of Gynecological Surgery, University School of Medicine, Jaczewskiego 8, 20-954 Lublin, Poland.
Oncol Rep. 2003 Jul-Aug;10(4):1039-43.
Microsatellite instability (MSI) is detected in about 20-25% of endometrial cancers (ECs). Incidence of this alteration correlates with lack of expression of certain mismatch repair genes such as hMLH1 and hMSH2. Although assessment of several markers has been proposed for identification of microsatellite unstable tumours, BAT-26, a mononucleotide microsatellite repeat, has been shown to be highly efficient when used as a single marker. The aim of the study was to evaluate instability within BAT-26 and expression of hMLH1 and hMSH2 proteins in sporadic endometrial cancer as well as to correlate these findings with histopathologic and clinical characteristics of tumours. Samples of 88 (74 endometrioid and 14 non-endometrioid) ECs were investigated for instability within BAT-26 by means of PCR and expression of hMLH1 and hMSH2 proteins using immunohistochemistry. BAT-26 MIS was discovered in 23.9% of endometrial cancers. Incidence of MSI did not correlated with grade, stage or depth of invasion. BAT-26 MSI was more frequent in non-endometrioid compared to endometrioid tumours (35.7% vs. 21.6%, respectively), but the difference was not statistically significant. Lack of hMLH1 and hMSH2 protein expression was detected in 21.6 and 15.9% of ECs, respectively, and did not correlate with clinicopathologic features of tumours. Loss of both hMLH1 and hMSH2 protein expression was similar in BAT-26 stable and unstable cancers. All cases of non-endometrioid tumours with BAT-26 MSI were positive for hMLH1. We can conclude that BAT-26 used alone may not be a reliable marker for identification of sporadic ECs with microsatellite instability induced by deficient expression of hMLH1 and hMSH2.
约20%-25%的子宫内膜癌（EC）中可检测到微卫星不稳定性（MSI）。这种改变的发生率与某些错配修复基因（如hMLH1和hMSH2）的表达缺失相关。尽管已提出评估多种标志物以识别微卫星不稳定肿瘤，但单核苷酸微卫星重复序列BAT-26作为单一标志物使用时已显示出高效性。本研究的目的是评估散发性子宫内膜癌中BAT-26的不稳定性以及hMLH1和hMSH2蛋白的表达，并将这些发现与肿瘤的组织病理学和临床特征相关联。通过PCR研究了88例EC（74例子宫内膜样癌和14例非子宫内膜样癌）样本中BAT-26的不稳定性，并使用免疫组织化学检测hMLH1和hMSH2蛋白的表达。在23.9%的子宫内膜癌中发现了BAT-26微卫星不稳定性（MIS）。MSI的发生率与分级、分期或浸润深度无关。与子宫内膜样肿瘤相比，非子宫内膜样肿瘤中BAT-26 MSI更常见（分别为35.7%和21.6%），但差异无统计学意义。分别在21.6%和15.9%的EC中检测到hMLH1和hMSH2蛋白表达缺失，且与肿瘤的临床病理特征无关。在BAT-26稳定和不稳定的癌症中，hMLH1和hMSH2蛋白表达均缺失的情况相似。所有BAT-26 MSI的非子宫内膜样肿瘤病例hMLH1均为阳性。我们可以得出结论，单独使用BAT-26可能不是识别因hMLH1和hMSH2表达缺陷引起微卫星不稳定的散发性EC的可靠标志物。
