Khan A, Krishna M, Baker S P, Banner B F
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655, USA.
Mod Pathol. 1998 Aug;11(8):704-8.
Cathepsin B is a lysosomal cysteine proteinase associated with degradation of laminin. It is increased in colorectal carcinoma (CA). Laminin is a major component of basement membrane involved in cell-matrix interactions and tumor progression. The aim of this study was to correlate cathepsin B and tumor-associated laminin in colorectal adenomas (ADs) with increasing grades of dysplasia and in invasive CAs. Forty-five ADs (8 tubular, 16 tubulovillous, 21 villous), 13 adenomas with high-grade dysplasia/carcinoma in situ (AHDs), and 17 invasive CAs were immunostained with polyclonal antibodies to cathepsin B and laminin. Statistical analysis was performed using exact linear by linear association test and Spearman rank correlation coefficient. Cathepsin B-positive tumor cells were seen in 30 (67%) ADs, 13 (100%) AHDs, and 17 (100%) CAs. The grade of cathepsin B staining was significantly increased in AHDs and CAs, compared with ADs (P < .0001). Laminin was continuous in all of the ADs and discontinuous or fragmented in the AHDs and CAs (P < .0001). The degree of cathepsin B staining in tumor cells also correlated with breakdown of laminin. Increased cathepsin B expression and decrease in tumor-associated laminin might suggest a mechanism for progression of ADs to CAs.
组织蛋白酶B是一种与层粘连蛋白降解相关的溶酶体半胱氨酸蛋白酶。它在结直肠癌(CA)中含量增加。层粘连蛋白是基底膜的主要成分,参与细胞与基质的相互作用以及肿瘤进展。本研究的目的是探讨结直肠腺瘤(AD)中组织蛋白酶B和肿瘤相关层粘连蛋白与发育异常程度增加以及浸润性CA之间的相关性。45例AD(8例管状、16例管状绒毛状、21例绒毛状)、13例高级别发育异常/原位癌(AHD)和17例浸润性CA用抗组织蛋白酶B和层粘连蛋白的多克隆抗体进行免疫染色。采用精确线性关联检验和Spearman等级相关系数进行统计分析。在30例(67%)AD、13例(100%)AHD和17例(100%)CA中可见组织蛋白酶B阳性肿瘤细胞。与AD相比,AHD和CA中组织蛋白酶B染色分级显著增加(P <.0001)。层粘连蛋白在所有AD中呈连续性,在AHD和CA中呈间断性或片段性(P <.0001)。肿瘤细胞中组织蛋白酶B染色程度也与层粘连蛋白的破坏相关。组织蛋白酶B表达增加和肿瘤相关层粘连蛋白减少可能提示AD进展为CA的一种机制。