Mayer B, Johnson J P, Leitl F, Jauch K W, Heiss M M, Schildberg F W, Birchmeier W, Funke I
Department of Surgery, University of Munich, Germany.
Cancer Res. 1993 Apr 1;53(7):1690-5.
Expression of the epithelial cell adhesion molecule E-cadherin in primary and metastatic gastric carcinoma was examined using immunohistochemical analyses. Compared to normal mucosa, 92% of the primary tumors (n = 60) showed reduced E-cadherin expression, suggesting that down-regulation of this cell adhesion molecule is a common early event in gastric tumorigenesis. No significant correlation was found between E-cadherin expression and tumor diameter, lymphatic vessel invasion, Borrmann classification, lymph node status, or manifest metastases. Although advanced tumors (tumor stage 3/4) showed a loss of E-cadherin-positive cells (< or = 50% cells/lesion, P = 0.0168), the most significant correlation was observed between low E-cadherin expression and cellular dedifferentiation (grading 3/4, P = 0.0001) and disintegration of tissue architecture (Lauren and WHO classifications, P = 0.0001). Low E-cadherin expression (< or = 50% cells/lesion) was associated with tumor recurrence (P = 0.0013) and mortality (P = 0.0246). E-cadherin expression in metastatic lesions (n = 58) also correlated with the degree of glandular differentiation (P = 0.0001). Significant correlation (rs = 0.686) was observed between E-cadherin expression in primary and metastatic lesions from individual patients (n = 39). However, while metastases derived from E-cadherin-negative tumors remained negative, those originating from E-cadherin-positive tumors frequently demonstrated increased levels of expression. Evaluation of multiple metastases in 11 patients revealed uniformly strong E-cadherin expression in liver metastases, suggesting a possible regulatory role of the microenvironment.
采用免疫组织化学分析方法检测原发性和转移性胃癌中上皮细胞粘附分子E-钙粘蛋白的表达情况。与正常黏膜相比,92%的原发性肿瘤(n = 60)显示E-钙粘蛋白表达降低,提示该细胞粘附分子的下调是胃癌发生过程中常见的早期事件。E-钙粘蛋白表达与肿瘤直径、淋巴管侵犯、Borrmann分类、淋巴结状态或明显转移之间未发现显著相关性。尽管晚期肿瘤(肿瘤分期3/4)显示E-钙粘蛋白阳性细胞减少(≤50%细胞/病灶,P = 0.0168),但E-钙粘蛋白低表达与细胞去分化(分级3/4,P = 0.0001)和组织结构破坏(Lauren和WHO分类,P = 0.0001)之间的相关性最为显著。E-钙粘蛋白低表达(≤50%细胞/病灶)与肿瘤复发(P = 0.0013)和死亡率(P = 0.0246)相关。转移性病灶(n = 58)中的E-钙粘蛋白表达也与腺管分化程度相关(P = 0.0001)。在个体患者(n = 39)的原发性和转移性病灶中观察到E-钙粘蛋白表达之间存在显著相关性(rs = 0.686)。然而,虽然源自E-钙粘蛋白阴性肿瘤的转移灶仍为阴性,但源自E-钙粘蛋白阳性肿瘤的转移灶通常显示表达水平升高。对11例患者的多个转移灶进行评估发现,肝转移灶中E-钙粘蛋白表达均一致较强,提示微环境可能具有调节作用。