肝门部胆管癌病理学及分子生物学特征的研究

Pathologic and molecular biologic characteristics of hilar cholangiocarcinomas

目的探讨肝门部胆管癌的病理学和分子生物学特征。方法分析68例肝门部胆管癌病例的病理学类型、神经和淋巴结浸润发生率;比较不同分化程度组患者血清CA19-9和CEA含量;免疫组织化学法观察肿瘤预后相关基因产物Her-1、Her-2、p170、血管内皮生长因子(VEGF)及突变型p53蛋白;细胞角蛋白CK7、CK18、CK19、CK20;增殖相关蛋白Ki-67、Top-Ⅱ的表达情况。结果68例患者肿瘤病理学类型全部为腺癌,中、低分化腺癌占85.29%;神经浸润发生率为91.18%、淋巴结浸润率为27.94%。高、中、低分化腺癌组,患者血清CA19-9、CEA含量之间的差异无统计学意义(P>0.05)。Her-1、Her-2、p170、VEGF和突变型p53阳性表达率分别为26.1%、21.7%、51.2%、36.0%和48.8%。CK7、CK18、CK19阳性表达率均为100%。Ki-67、Top-Ⅱ阳性率分别为93.3%、83.7%;Kappa检验显示,Ki-67与Top-Ⅱ对胆管癌细胞增殖程度的检验效果一致性较好(P<0.01)。结论肝门部胆管癌以中、低分化腺癌为主;肿瘤具有很高的神经浸润发生率;血清CA19-9、特异性角蛋白检测有助于肝门部胆管癌的鉴别诊断;Ki-67与Top-Ⅱ对肿瘤增值程度的检测效果相当。

Objective To investigate the pathologic and molecular biologic characteristics of hilar cholangiocarcinomas. Methods Sixty-eight patients with hilar cholangiocarcinomas were reviewed,and the pathologic types and incidence of perineural invasion and lymph node metastasis were summarized. Contents of serum CA19-9 and CEA were compared. The expression of protein Her-1, Her-2, p170, VEGF, p53, CK7, CK18, CK19, CK20, Ki-67 and Top- Ⅱ was detected by using immunohistochemical method. Resuits All of the tumors were adenocarcinoma and 85.29% of those were moderately and poorly differentiated. The incidence of perineural invasion and lymph node metastasis was 91.18% （62/68） and 27.94% （19/68） ,respectively. There was no significant difference in the contents of serum CA19-9 and CEA among well-, moderately- and poorly-differentiated adenocarcinoma groups （ P 〉 0.05 ）. Her-1 （ 26.1% ）, Her-2 （21.7%） ,p170 （51.2%） ,VEGF （36%） and mutant p53 （48.8%） were expressed in the specimens,respectively. Protein Ck7 ,CK18 and CK19 were expressed in all of the specimens. Ki-67 （93.3%） and Top- Ⅱ （83.7%） were also expressed in the specimens, and there was a good concordance between Ki-67 and Top- Ⅱ in detecting the proliferation of tumor through Kappa analysis （P 〈 0.01 ）. Conclusion Hilar cholangiocarcinoma is a malignant disease which is mainly composed of moderately- and poorlydifferentiated adenocarcinoma. The incidence of perineural invasion in hilar cholangiocarcinoma is very high. Contents of serum CA19-9 and special keratin are helpful to diagnose this disease. Ki-67 and Top- Ⅱ have the same efficacy in detecting the proliferation of hilar cholangiocarcinomas.