Department of Pathology, Medical School, University of Valencia, Spain.
Arch Pathol Lab Med. 2011 Aug;135(8):1001-9. doi: 10.5858/2010-0071-OAR1.
Synovial sarcomas are mesenchymal tumors with epithelial nature and comprise biphasic and monophasic fibrous subtypes. However, factors determining epithelial or spindle cell differentiation are still unexplored. Aberrant epithelial-mesenchymal transition has been implicated in the pathogenesis of diverse human malignancies.
To analyze the correlation between cellular phenotype and expression of proteins associated with different epithelial-mesenchymal transition-related pathways.
Immunohistochemical analysis of E-cadherin, Snail, Slug, and dysadherin, components of the Wnt/wingless and PI3K/Akt pathways, was performed on 14 biphasic and 27 monophasic fibrous tumors.
In monophasic fibrous tumors, increased expression of Snail (17 of 27; 63%), Slug (18 of 27; 67%), and dysadherin (14 of 27; 52%) and activation of Wnt (nucleocytoplasmic β-catenin accumulation in 63%; n = 27; and positive expression of GSK3 and pGSK3 in 24 of 27 [89%] and 21 of 27 [78%], respectively) and PI3K/Akt (Akt: 22 of 27 [81%]; pAkt: 25 of 27 [93%]; and PI3K: 20 of 27 [74%]) signaling correlated significantly with inactivated E-cadherin expression (1 of 27; 4%) (all P < .05). In contrast, preserved E-cadherin expression (12 of 14; 86%) in the glandular component of the biphasic subtype was associated with significantly decreased Snail (3 of 14; 21%) (P = .02) and dysadherin (2 of 14; 14%) expression (P < .001).
Overexpression of Snail, Slug, and dysadherin and activation of Wnt and PI3K/Akt signaling was associated with inactivated E-cadherin in the spindle cells of monophasic fibrous synovial sarcomas, further supporting the hypothesis that this subtype may have developed through neoplastic epithelial-mesenchymal transition.
滑膜肉瘤是一种具有上皮性质的间叶性肿瘤，包括双相型和单相纤维型亚型。然而，决定上皮或梭形细胞分化的因素仍未被探索。异常的上皮-间充质转化已被牵连入多种人类恶性肿瘤的发病机制中。
分析细胞表型与不同上皮-间充质转化相关途径相关蛋白表达之间的相关性。
对 14 例双相型和 27 例单相纤维型滑膜肉瘤进行 E-钙黏蛋白、Snail、Slug 和黏附素的免疫组织化学分析，这些蛋白是 Wnt/wingless 和 PI3K/Akt 途径的组成部分。
在单相纤维型肿瘤中，Snail（27 例中的 17 例；63%）、Slug（27 例中的 18 例；67%）和黏附素（27 例中的 14 例；52%）的表达增加，Wnt 通路被激活（核质 β-连环蛋白在 63%（27 例）中积累；阳性表达 GSK3 和 pGSK3 在 24/27[89%]和 21/27[78%]中）和 PI3K/Akt（Akt：27 例中的 22 例；81%）；pAkt：27 例中的 25 例；93%）和 PI3K（27 例中的 20 例；74%）与 E-钙黏蛋白表达失活（1/27；4%）（均 P<.05）显著相关。相反，双相型肿瘤中腺管成分的 E-钙黏蛋白表达正常（14 例中的 12 例；86%）与 Snail（14 例中的 3 例；21%）（P=.02）和黏附素（14 例中的 2 例；14%）表达显著减少相关（P<.001）。
Snail、Slug 和黏附素的过表达以及 Wnt 和 PI3K/Akt 信号通路的激活与单相纤维型滑膜肉瘤梭形细胞中 E-钙黏蛋白失活有关，这进一步支持了该亚型可能通过肿瘤上皮-间充质转化而发展的假说。
