Lindmark G, Gerdin B, Påhlman L, Glimelius B, Gehlsen K, Rubin K
Department of Surgery, University of Uppsala, Sweden.
Eur J Surg Oncol. 1993 Feb;19(1):50-60.
The expression and distribution of integrin subunits alpha 2 and alpha 3 and two of their putative ligands, type IV collagen and laminin, were examined by immunohistochemistry in specimens from 33 consecutive patients operated on for colorectal adenocarcinomas. Both tumour cells and normal epithelium expressed the alpha 2 and alpha 3 subunits. Two typical patterns of expression could be discerned; a basolateral expression and a diffuse cytoplasmic expression. The stained tumour specimens were assessed according to (i) distribution of integrin expression (diffusely cytoplasmic or basolateral), (ii) continuity in basolateral integrin expression, and (iii) interconnection of integrin expression and expression of type IV collagen and laminin. These parameters were then related to tumour differentiation, tumour stage according to Dukes' classification, DNA-ploidy and patient survival (median observation time was 30 months; range 24-35). The continuity in the basolateral expression of alpha 3 but not of alpha 2, correlated with the basal membrane expression of type IV collagen (P < 0.001). Loss of continuity in the basolateral expression of both integrins was significantly related to impaired tumour differentiation (alpha 2 P = 0.02; alpha 3 P = 0.01), more advanced Dukes' stage (alpha 2 = 0.07, alpha 3 P < 0.001), survival rate (both integrins P < 0.05), but not to DNA-ploidy. These data suggest that determination of the pattern of expression of the integrin subunits alpha 2 and alpha 3 in the preoperative biopsy and the surgical specimen could be used as a prognostic indicator.
采用免疫组织化学方法,对33例连续接受结直肠癌手术患者的标本进行检测,观察整合素α2和α3亚基及其两种假定配体Ⅳ型胶原和层粘连蛋白的表达与分布情况。肿瘤细胞和正常上皮细胞均表达α2和α3亚基。可识别出两种典型的表达模式:基底外侧表达和弥漫性胞质表达。根据以下标准对染色的肿瘤标本进行评估:(i)整合素表达的分布(弥漫性胞质或基底外侧);(ii)基底外侧整合素表达的连续性;(iii)整合素表达与Ⅳ型胶原和层粘连蛋白表达的相互关系。然后将这些参数与肿瘤分化、根据Dukes分期的肿瘤分期、DNA倍体和患者生存率(中位观察时间为30个月;范围24 - 35个月)相关联。α3而非α2的基底外侧表达连续性与Ⅳ型胶原的基底膜表达相关(P < 0.001)。两种整合素基底外侧表达的连续性丧失与肿瘤分化受损(α2,P = 0.02;α3,P = 0.01)、更晚期的Dukes分期(α2,P = 0.07;α3,P < 0.001)、生存率(两种整合素,P < 0.05)显著相关,但与DNA倍体无关。这些数据表明,术前活检和手术标本中整合素α2和α3亚基表达模式的测定可作为一种预后指标。