Ioachim E, Charchanti A, Briasoulis E, Karavasilis V, Tsanou H, Arvanitis D L, Agnantis N J, Pavlidis N
Department of Pathology, Medical School, University of Ioannina, 45110 Ioannina, Greece.
Eur J Cancer. 2002 Dec;38(18):2362-70. doi: 10.1016/s0959-8049(02)00210-1.
The immunohistochemical expression of the extracellular matrix (ECM) components tenascin (TN), fibronectin (FN), collagen type IV (Coll) and laminin (LN), and their possible relationships were studied in a series of 134 operable breast cancer cases. Their expression was also compared with the expression of the proteolytic enzyme cathepsin D (CD), the adhesion molecule CD44 standard form (CD44s) and other known factors to clarify the prognostic value and role of these molecules in tumour progression and metastasis. TN expression in the tumour stroma was positively correlated with tumour grade and size, CD44s expression, tumour and stromal CD expression as well as with FN, laminin and Coll expression in the same areas. TN expression was inverse correlated with ER status. Its expression at the invasion front was only positively correlated with the lymph node status. Survival analysis showed an increased mortality risk associated with high levels of TN expression. In multivariate analysis, among the ECM proteins, only TN expression was independently correlated with patients' survival. FN expression was positively correlated with lymph node involvement, with the proliferation-associated index Ki-67 and stromal CD expression. Survival analysis showed an increased mortality risk associated with a high level of FN expression. Coll expression was positively correlated with the tumour size and LN expression. An inverse relationship of Coll expression with ER and PgR receptor status was also found. LN expression was positively correlated with tumour and stromal CD expression, with the proliferation-associated index Ki-67 and inversely with ER receptor status. The observed alterations in the expression of ECM proteins in breast cancer tissue and their correlations with the proteolytic enzyme CD and the adhesion molecule CD44s, suggest an involvement in cancer progression. In addition, overexpression of stromal TN and FN seems to have negative prognostic value in breast cancer patients.
在134例可手术乳腺癌病例中，研究了细胞外基质（ECM）成分腱生蛋白（TN）、纤连蛋白（FN）、IV型胶原（Coll）和层粘连蛋白（LN）的免疫组化表达及其可能的关系。还将它们的表达与蛋白水解酶组织蛋白酶D（CD）、粘附分子CD44标准型（CD44s）及其他已知因子的表达进行比较，以阐明这些分子在肿瘤进展和转移中的预后价值及作用。肿瘤基质中TN的表达与肿瘤分级、大小、CD44s表达、肿瘤及基质CD表达以及同一区域的FN、层粘连蛋白和Coll表达呈正相关。TN表达与雌激素受体（ER）状态呈负相关。其在浸润前沿的表达仅与淋巴结状态呈正相关。生存分析显示，TN高表达与死亡风险增加相关。多因素分析中，在ECM蛋白中，只有TN表达与患者生存独立相关。FN表达与淋巴结受累、增殖相关指数Ki-67及基质CD表达呈正相关。生存分析显示，FN高表达与死亡风险增加相关。Coll表达与肿瘤大小及LN表达呈正相关。还发现Coll表达与ER和孕激素受体（PgR）状态呈负相关。LN表达与肿瘤及基质CD表达、增殖相关指数Ki-67呈正相关，与ER受体状态呈负相关。在乳腺癌组织中观察到的ECM蛋白表达改变及其与蛋白水解酶CD和粘附分子CD44s的相关性，提示其参与了癌症进展。此外，基质TN和FN的过表达似乎对乳腺癌患者具有负面预后价值。
