Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Hum Pathol. 2010 Aug;41(8):1128-37. doi: 10.1016/j.humpath.2009.12.014. Epub 2010 Apr 8.
Basal cell carcinoma is a very common malignant skin tumor that rarely metastasizes but is often locally aggressive. In a number of studies conducted by different investigators, Bcl2, beta-catenin, cyclin D1, hMSH2, and alpha-smooth muscle actin have been reported to have potential for predicting basal cell carcinoma aggressiveness. However, these reports were inconclusive and sometimes contradictory. We therefore studied the expression and topographic locations (tumor versus stroma) of all these gene products in a group of clinically proven aggressive basal cell carcinomas (n = 30) and randomly selected control cases of nonaggressive basal cell carcinomas (n = 33). The results were subjected to statistical analysis with Mann-Whitney test and logistic regression. The accuracy of the resulting significant discriminating criteria was further tested using the omnibus tests of model coefficients. With multivariate analysis, differential expression of Bcl-2, beta-catenin, and cyclin D1 was not significantly different between aggressive and nonaggressive tumors. hMSH2 expression was up-regulated in the aggressive tumors (P = .005). Alpha-smooth muscle actin was expressed by tumor cells in both study groups, but stromal expression of alpha-smooth muscle actin was restricted to the aggressive tumors and highly predictive of aggressive behavior (P < .001; accuracy, 87%). Logistic regression combining the expression of alpha-smooth muscle actin and hMSH2 yielded a predictive model with 97% accuracy (P < .001). These data show conclusively that aggressive basal cell carcinomas express alpha-smooth muscle actin in the stroma, whereas nonaggressive basal cell carcinomas express alpha-smooth muscle actin in the tumor cells, and that stromal expression of alpha-smooth muscle actin is an accurate, reliable, and easy to use marker of aggressiveness in basal cell carcinomas and can be used in clinical practice for surgical therapeutic decisions.
基底细胞癌是一种非常常见的恶性皮肤肿瘤，很少转移，但往往局部侵袭性强。在不同研究者进行的多项研究中，Bcl2、β-连环蛋白、细胞周期蛋白 D1、hMSH2 和α-平滑肌肌动蛋白被报道具有预测基底细胞癌侵袭性的潜力。然而，这些报告尚无定论，有时甚至相互矛盾。因此，我们研究了一组经临床证实侵袭性基底细胞癌（n = 30）和随机选择的非侵袭性基底细胞癌（n = 33）中所有这些基因产物的表达和拓扑位置（肿瘤与基质）。结果采用 Mann-Whitney 检验和逻辑回归进行统计分析。使用模型系数的整体检验进一步测试了由此产生的显著判别标准的准确性。通过多变量分析，侵袭性和非侵袭性肿瘤之间 Bcl-2、β-连环蛋白和细胞周期蛋白 D1 的差异表达无显著差异。hMSH2 在侵袭性肿瘤中表达上调（P =.005）。α-平滑肌肌动蛋白在两组研究中的肿瘤细胞中均有表达，但基质中α-平滑肌肌动蛋白的表达仅限于侵袭性肿瘤，且对侵袭性行为具有高度预测性（P <.001；准确性为 87%）。将α-平滑肌肌动蛋白和 hMSH2 的表达相结合的逻辑回归得出了一个具有 97%准确性的预测模型（P <.001）。这些数据明确表明，侵袭性基底细胞癌在基质中表达α-平滑肌肌动蛋白，而非侵袭性基底细胞癌在肿瘤细胞中表达α-平滑肌肌动蛋白，并且基质中α-平滑肌肌动蛋白的表达是基底细胞癌侵袭性的准确、可靠且易于使用的标志物，可用于临床实践中的手术治疗决策。
