Scimeca Manuel, Antonacci Chiara, Colombo Daniele, Bonfiglio Rita, Buonomo Oreste Claudio, Bonanno Elena
Anatomic Pathology Section, Department of Biomedicine and Prevention, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy.
TMALab s.r.l., Spin-off of University of Tor Vergata, Rome, Italy.
Tumour Biol. 2016 Apr;37(4):5427-35. doi: 10.1007/s13277-015-4361-7. Epub 2015 Nov 12.
Despite the screening program, breast cancer is the commonest cause of cancer death in women in the industrialized world. In this study, we investigate the correlation among poorly differentiated carcinoma, epithelial to mesenchymal transition (EMT) phenomenon, and expression of NF-kB, Sonic Hedgehog (SHH), K-RAS, and PTX3 in breast cancer in 100 breast biopsies. Samples were classified as follows: 30 benign lesions (BL), 30 ductal infiltrating carcinomas low grade (MLG1), and 40 ductal infiltrating carcinomas high grade (MLG3). Expression of vimentin, CD44, β-catenin, NF-kB, SHH, K-RAS, CD44, and PTX3 was studied by immunohistochemistry. The different rate of cells with vimentin, nuclear β-catenin, and CD44 expression in MLG3 as compared with MLG1 and BL suggested that the process of de-differentiation of breast cancer cells could be related to the EMT. Our results showed a significant increase in NF-kB signal in MLG3 (2.33 ± 0.77) with respect to MLG1 (1.26 ± 0.55) and BL (0.86 ± 0.52). SHH expression appeared low in BL (1.00 ± 0.41) and homogenously widespread in MLG1 (1.23 ± 0.63) and MLG3 (1.56 ± 0.54). An important increase in K-RAS signal was observed in MLG3 compared to that in BL (2.20 ± 0.69 vs 0.82 ± 0.59). As regards PTX3, we observed a strong expression in MLG3 (2.00 ± 0.78) with respect to BL (0.58 ± 0.55) and MLG1 (1.53 ± 0.76). The recurring expression of NF-kB, SHH, K-RAS, and PTX3 in vimentin- and CD44-positive breast cancer cells allows to speculate that breast cells acquire the ability to express these molecules in concomitance to EMT phenomenon.
尽管有筛查项目，但在工业化国家，乳腺癌仍是女性癌症死亡的最常见原因。在本研究中，我们调查了100例乳腺活检组织中低分化癌、上皮-间质转化（EMT）现象以及NF-κB、音猬因子（SHH）、K-RAS和PTX3在乳腺癌中的表达之间的相关性。样本分类如下：30例良性病变（BL）、30例低级别导管浸润癌（MLG1）和40例高级别导管浸润癌（MLG3）。通过免疫组织化学研究波形蛋白、CD44、β-连环蛋白、NF-κB、SHH、K-RAS、CD44和PTX3的表达。与MLG1和BL相比，MLG3中波形蛋白、核β-连环蛋白和CD44表达的细胞比例不同，这表明乳腺癌细胞的去分化过程可能与EMT有关。我们的结果显示，与MLG1（1.26±0.55）和BL（0.86±0.52）相比，MLG3中NF-κB信号显著增加（2.33±0.77）。SHH表达在BL中较低（1.00±0.41），在MLG1（1.23±0.63）和MLG3（1.56±0.54）中均匀分布。与BL相比（2.20±0.69对0.82±0.59），MLG3中观察到K-RAS信号显著增加。至于PTX3，与BL（0.58±0.55）和MLG1（1.53±0.76）相比，我们在MLG3中观察到强表达（2.00±0.78）。NF-κB、SHH、K-RAS和PTX3在波形蛋白和CD44阳性乳腺癌细胞中的反复表达使我们推测，乳腺细胞在EMT现象的同时获得了表达这些分子的能力。
