Expression of CD34, α-smooth muscle actin, and transforming growth factor β1 in squamous intraepithelial lesions and squamous cell carcinoma of the larynx and hypopharynx
Expression of CD34, α-smooth muscle actin, and transforming growth factor β1 in squamous intraepithelial lesions and squamous cell carcinoma of the larynx and hypopharynx
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DOI：
10.1016/j.humpath.2004.10.011
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Gale, N
中科院分区：
文献类型：
--
作者：
Kojc, N;Zidar, N;Gale, N
研究目的：越来越多的证据表明，间质反应在癌症中具有重要的诊断和预后意义。最近的研究表明，CD34阳性的基质细胞和肌成纤维细胞可能在宿主对侵袭性癌症的反应中发挥重要作用。本研究的目的是分析CD34、α-平滑肌肌动蛋白(SMA)和转化生长因子β1(TGFbeta1)在喉和下咽鳞状上皮内病变(SILs)和鳞状细胞癌(SCC)中的表达，探讨其意义，并探讨其形成机制。方法：采用免疫组织化学方法，对42例喉鳞状上皮内病变(SILs)和12例喉鳞状细胞癌(SCC)标本进行免疫组织化学染色。结果：正常喉粘膜和SILs间质中有散在分布的CD34阳性细胞，但未见SMA阳性肌成纤维细胞。鳞癌间质中有SMA阳性的肌成纤维细胞，但无CD34阳性的间质细胞。这种间质反应模式也可以在瘤周区域观察到。在邻近正常组织中，可见CD34阳性间质细胞，无肌成纤维细胞。我们发现TGFbeta1在癌细胞中的表达比在正常喉上皮中更强，在正常黏膜的间质细胞上TGFp1受体也呈阳性表达。在鳞状细胞癌中，许多肌成纤维细胞表达TGFbeta1及其受体。结论：CD34阳性间质细胞的消失和SMA阳性间质成纤维细胞的出现与喉鳞状细胞癌的转化有关。这种间质反应模式不仅在肿瘤中发现，而且在肿瘤周围区域也发现，肿瘤周围区域定义为侵袭性肿瘤前沿和邻近正常组织之间的宿主组织带。我们的发现也支持在喉癌发生过程中，癌细胞中过度产生的TGFbeta1是基质细胞向肌成纤维细胞转化的机制之一。(C)2005 Elsevier Inc.保留所有权利。
Aim of the study: There is increasing evidence that stromal reaction in cancer has an important diagnostic and prognostic significance. Recent studies have shown that CD34-positive stromal cells and myofibroblasts may play an important role in host response to invasive cancer. The aim of our study was to analyze the expression of CD34, alpha-smooth muscle actin (SMA), and transforming growth factor betal (TGFbeta1) in squamous intraepithelial lesions (SILs) and squamous cell carcinoma (SCC) of the larynx and hypopharynx, to establish their significance, and to elucidate the mechanism of myofibroblast formation.Methods: Immunohistochemistry was performed on samples of 42 resected larynges and 12 laryngeal biopsies of SILs and SCC using antibodies against SMA, CD34, CD31, TGFbeta1, and TGFbeta1 receptors. The expression of TGFbeta1 mRNA was detected with RNA in situ hybridization using specific oligonucleotides for TGFbeta1.Results: The stroma in normal laryngeal mucosa and SILs contained scattered CD34-positive cells, but there were no SMA-positive myofibroblasts. In contrast, the stroma of SCC contained SMA-positive myofibroblasts, but there were no CD34-positive stromal cells. This pattern of stromal reaction was also observed in the peritumoral zone. In adjacent normal tissue, there were CD34-positive stromal cells and no myofibroblasts. We found more intense TGFbeta1 expression in carcinoma cells than in the normal laryngeal epithelium and positive staining for both TGFpl receptors on stromal cells of the normal mucosa. In SCC, many myofibroblasts expressed TGFbeta1 and both receptors for TGFbeta1. Expression of TGFbeta1 mRNA was similar to expression of TGFbeta1 protein.Conctusion: Our study shows that disappearance of CD34-positive stromal cells and appearance of SMA-positive stromal myofibroblasts are associated with transformation of laryngeal SILs to SCC. This pattern of stromal reaction was found not only in the tumor but also in the peritumoral zone, defined as a band of host tissue between the invasive tumor front and adjacent normal tissue. Our findings also support the suggestion that overproduced TGFbeta1 in carcinoma cells mediates one of the mechanisms of transformation of stromal cells to myofibroblasts in laryngeal carcinogenesis. (C) 2005 Elsevier Inc. All rights reserved.