Saha Baisakhi, Chaiwun Benjaporn, Imam Sarah S, Tsao-Wei Denice D, Groshen Susan, Naritoku Wesley Y, Imam S Ashraf
Gene Therapy Program, Huntington Medical Research Institutes, Pasadena, CA 91101-1830, USA.
Anticancer Res. 2007 Nov-Dec;27(6B):3903-8.
The aim of the present study was to evaluate E-cadherin, whose expression remains poorly understood in the intercellular adhesion of metastatic breast cancer cells in bone, the most prevalent site for metastatic growth.
An immunohistochemical staining method was used for the localization of E-cadherin protein in tissue biopsy specimens of normal breast (n = 9) and well- (n = 8), moderately (n = 8) or poorly (n = 14) differentiated invasive primary breast cancer and metastatic breast cancer in bone (n = 17). The expression patterns of E-cadherin were classified as homogeneous (most cells exhibiting positivity), heterogeneous (a few scattered patches of cells with positivity) or negative (cells with undetectable positivity).
Normal breast epithelial cells showed homogeneous overexpression of E-cadherin in all cases. A progressive and statistically significant reduction of E-cadherin expression was detected in the histologically well- to moderately to poorly differentiated breast cancer cells (p < 0.001). The clumps of invasive primary breast cancer cells in CD-31-positive blood vessels exhibited E-cadherin expression. Moreover, as compared to the poorly differentiated breast cancer cells, a significantly increased frequency of the metastatic breast cancer cells in bone exhibited homogeneous expression of E-cadherin in 15 out of 17 and heterogeneous expression in the remaining 2 cases (McNemar Exact p < 0.001). This is the first demonstration of membranous overexpression of E-cadherin on metastatic breast cancer cells in bone; the high frequency of its expression may have a role in the intercellular adhesion of metastatic cells in bone.
本研究旨在评估E-钙黏蛋白，其在骨转移乳腺癌细胞的细胞间黏附中的表达仍知之甚少，而骨是转移瘤生长最常见的部位。
采用免疫组织化学染色方法对正常乳腺组织活检标本（n = 9）、高分化（n = 8）、中分化（n = 8）或低分化（n = 14）浸润性原发性乳腺癌以及骨转移乳腺癌（n = 17）中的E-钙黏蛋白进行定位。E-钙黏蛋白的表达模式分为均匀型（大多数细胞呈阳性）、异质型（少数散在阳性细胞团块）或阴性（未检测到阳性细胞）。
所有病例中正常乳腺上皮细胞均显示E-钙黏蛋白均匀过表达。在组织学上高分化至中分化再到低分化的乳腺癌细胞中检测到E-钙黏蛋白表达呈逐渐且具有统计学意义的降低（p < 0.001）。CD-31阳性血管中浸润性原发性乳腺癌细胞团块呈现E-钙黏蛋白表达。此外，与低分化乳腺癌细胞相比，骨转移乳腺癌细胞中E-钙黏蛋白均匀表达的频率显著增加，17例中有15例，其余2例为异质型表达（McNemar确切概率法，p < 0.001）。这是首次证明骨转移乳腺癌细胞上E-钙黏蛋白的膜性过表达；其高表达频率可能在骨转移细胞的细胞间黏附中起作用。
