胆囊良恶性病变中胆囊星形细胞标记物及其调控因子的表达研究

目的 探讨胆囊腺癌、癌旁组织和慢性胆囊炎组织中GSCs和其调控因子TGF β1mRNA和CTGFmRNA表达水平及其临床病理意义。方法 108例胆囊腺癌、46例癌旁组织和35例慢性胆囊炎手术切除标本常规石蜡包埋切片，GSCs染色方法为平滑肌肌动蛋白（α SMA）单抗EnVisiomTM免疫组化法，TGF β1mRNA和CTGFmRNA染色方法为原位杂交法。结果 胆囊腺癌α SMA，TGF β1mRNA，CTGFmRNA表达阳性率及其评分明显高于癌旁组织和慢性胆囊炎（P<0.05或P<0.01）；但腺瘤癌变、肿块最大径<2cm、无淋巴结转移和未侵犯周围组织者的α SMA，TGF β1mRNA，CTGFmRNA表达阳性率及其评分明显高于低分化腺癌、肿块最大径≥2cm、淋巴结转移和侵犯周围组织器官者（P<0.05或P<0.01）；胆囊腺癌中α SMA，TGF β1mRNA，CTGFmRNA表达评分之间均呈高度密切正相关（α SMA vs TGF β1mRNA, r=0.82; α SMA vs CTGFmRNA r=0.75; TGF β1mRNA vs CTGFmRNA, r=0.78）结论 α SMA，TGF β1mRNA，CTGFmRNA均为反映胆囊腺癌进展、生物学行为及预后的重要生物学标记物，TGF β1和CTGF在活化GSCs方面可能具有重要调控作用。

Study on the expression of GSCs marker and it''''s regulated factor in benign and malignant gallbladder lesions

Abstract:Objective To study the distributions of gallbladder stellate cells (GSCs) and the expressions of TGF β1mRNA, CTGFmRNA in gallbladder adenocarcinoma, pericancerous tissues, and chronic cholecystitis, and their clinicopathological significance.Methods EnVisionTM immunohistochemistry of α SMA monconal antibody for GSCs or in situ hybridization for TGF β1mRNA and CTGFmRNA was used in paraffin embedded sections of the specimens of gallbladder adenocarcinoma (n=108), pericancerous tissues (n=46) and chronic cholecystitis (n=35). Results The positive expression rates and scores of α SMA, TGF β1mRNA, CTGFmRNA were significantly higher in specimens of gallbladder adenocacrcinoma than those in pericancerous tissues or chronic cholecystitis (P<0.01). The positive expression rates and scores of α SMA, TGF β1mRNA and CTGFmRNA were significantly higher in the cases of malignant adenoma, maximal diameter of tumor <2cm，with no lymphnode metastasis, and no invasion of regional tissues compared to those in cases of low differentiatedadenocarcinoma, maximal diameter of tumor ≥2cm, with lymphnode metastasis, and invasion of regional tissues (P<0.05 or P<0.01). High and close positive correlations were found among the expression scores of α SMA, TGF β1mRNA and CTGFmRNA in gallbladder adenocarcioma (α SMA vs TGF β1mRNA, r=0.82; α SMA vs CTGFmRNA, r=0.75; TGF β1mRNA vs CTGFmRNA, r=0.78).Conclusions The expressions of α SMA, TGF β1mRNA and CTGFmRNA might be important biological markers for reflecting the carcinogenesis, progression, biological behaviors and prognosis of gallbladder adenocarcinoms. TGF β1 and CTGF might have important regulatory effects on the activation of GSCs.