| Objective: Recent studies have found that stromal microenvironment has increasing role in the initiation and progression of cancer, not bystander but a key player, or even a potential initiator. As the main effector, a type of activated fibroblasts have been been found in tumorous stromal, and so called Carcinoma-associated-fibroblasts(CAFs) with theαSMA(+) and CD34(-) characteristic can promote the initiation and progression of cancer through the secretions such as TGF-β1, HGF.Esophageal squmous carcinoma(ESC) is one of the most common malignancies in China, more than 50% ESC patients in the world are Chinese, So ESC is a focused malignant tumor to be prevented and treated in our country. Many studies have shown ESC undergoes a multistage process from normal, precancerosis, early cancer to cancer. The research of stromal microenvironment in the process will be able to promote the development of study and treatment on ESC.The experiment was made to observe the expressions ofαSMA, CD34, TGF-β1 and HGF in initiation and progression of esophageal cancer. To explore the role of stromal CAFs and related protein in tumorous initiation and progression. To seek the potential significant clinical indicators on diagnosis and treatment, so as to provide a scientific basis for the diagnosis, treatment and prognosis of esophageal cancer.Methods: The S-P methods of immunohistochemistry was employed to measure the expression ofαSMA, CD34, TGF-β1 and HGF in 136 specimens of esophageal tissue, in which have 20 specimens of normal esophageal tissue, 26 specimens of low level intraepithelial neoplasia, 44 specimens of high level intraepithelial neoplasia, 23 specimens of early cancer, 23 specimens of advanced cancer. And every group's microvascular density(MVD) was counted. SPSS 13.0 was applied to analyze the results of experiment.Results:1 Expression ofαSMA in stromal fibroblasts of various esophageal lesionsThe normal esophageal stromal fibroblasts didn't expressαSMA (0/20), but the smooth muscle tissue and small vascular smooth muscle cells expressedαSMA. At low level intraepithelial neoplasia the positive expression rate ofαSMA began to increase gradually, the expression rate of adanced cancer group was 95.7%(22/23). The spindle positive cells were looked like silk ribbons surrounding the lesion tissue or tumorous nests. Results showed a ascendant trend inαSMA expression of stromal fibroblasts in the process of esophageal epithelial canceration. The expression was not obviously correlated with patient's gender,age. Significant difference has been found in all groups about the positive expression ofαSMA(χ~2=56.423, P=0.000).2 Expression of CD34 in stromal fibroblasts of various esophageal lesionsThe CD34 positive expression rate in normal esophageal stromal fibroblasts was 95.0%(19/20). At low level intraepithelial neoplasia the positive expression rate of CD34 began to decrease gradually,in adanced cancer group stromal fibroblasts didn't express CD34, Only endothelial cells expressed CD34. Results showed a descendant trend in CD34 expression of stromal fibroblasts in the process of canceration. The expression was not obviously correlated with patient's gender,age. Significant difference has been found in all groups about the positive expression of CD34(χ~2=51.977, P=0.000).3 Expression of TGF-β1 in epithelium and stromal fibroblasts of various esophageal lesions3.1 Expression of TGF-β1 in epithelium of various esophageal lesions The TGF-β1 positive expression rate in normal esophageal epithelium was 5.0%(1/20), the low level intraepithelial neoplasia group was 57.7%(15/26), the high level intraepithelial neoplasia group was 65.9%(29/44), the early cancer group was 43.5%(10/23) and the adanced cancer group was 13.0%(3/23). Results showed a fist ascendant and then descendant trend in TGF-β1 expression of epithelium in the process of canceration. The expression was not obviously correlated with patient's gender, age. Significant difference has been found in all groups about the positive expression of TGF-β1(χ~2=31.977, P=0.000).3.2 Expression of TGF-β1 in stromal fibroblasts of various esophageal lesionsThe normal esophageal stromal fibroblasts didn't express TGF-β1(0/20). At low level intraepithelial neoplasia the positive expression rate of TGF-β1 began to increase gradually, the expression rate of adanced cancer group was 60.9%(14/23). Results showed a ascendant trend in TGF-β1 expression of stromal fibroblasts in the process of canceration. The expression was not obviously correlated with patient's gender,age. Significant difference has been found in all groups about the positive expression of TGF-β1(χ~2=31.425, P=0.000).4 Expression of HGF in stromal fibroblasts of various esophageal lesionsThe normal esophageal stromal fibroblasts didn't express HGF (0/20). At low level intraepithelial neoplasia the positive expression rate of HGF began to increase gradually, the expression rate of adanced cancer group was 56.5%(13/23). Results showed a ascendant trend in HGF expression of stromal fibroblasts in the process of canceration. The expression was not obviously correlated with patient's gender,age. Significant difference has been found in all groups about the positive expression of HGF(χ~2=26.817,p=0.000).5 Expression correlation betweenαSMA and CD34, TGF-β1 in stromal fibroblasts of various esophageal lesionsThe expression ofαSMA in stromal fibroblasts of various esophageal lesions was inversely correlated with CD34(R=-0.762, P=0.000). The expression ofαSMA in stromal fibroblasts of various esophageal lesions was correlated with TGF-β1(R=0.419, P=0.000).6 The MVD of the various esophageal lesionsThe MVD value of normal esophagus was 12.33±1.68, The MVD of low level intraepithelial neoplasia was 15.72±1.97, The MVD of high level intraepithelial neoplasia was 20.91±2.20, The MVD of early cancer was 26.42±1.96, The MVD of adanced cancer was 30.01±2.35. The MVD was not obviously correlated with patient's gender, age. Significant difference has been found in all groups about The MVD value(P=0.000), and also in any two of all groups(P=0.000).Conclusions:1 With the process of esophageal squamous epithelial canceration, there were more stromal fibroblasts transforming into CAFs. Suggests that CAFs can induce esophageal squamous epithelial transforming and further developing.2 CAFs can contribute to the initiation and progression of ESC through factors such as TGF-β1, HGF.3 CAFs may promote microvascular formation in precancerous stage, and thus promote the initiation and progression of esophageal cancer.4 Indicates CAFs and the related factors such as TGF-β1, HGF in esophageal precancerosis probably are good prognosis indicators. |
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