Solakidi S, Tiniakos D G, Petraki K, Stathopoulos G P, Markaki I, Androulakis G, Sekeris C E
Institute of Biological Research, National Hellenic Research Foundation, Athens, Greece.
Histol Histopathol. 2003 Oct;18(4):1181-8. doi: 10.14670/HH-18.1181.
Trypsin and its specific inhibitor, TATI (tumour-associated trypsin inhibitor), are expressed in normal human pancreas and in a variety of tumours. The aim of the present study was to assess the parallel expression of trypsin and TATI in colorectal cancer, in comparison with their expression in normal epithelial tissue, since proteases and their inhibitors are thought to be co-expressed in malignant neoplasms. We also assessed the possible significance of their expression as a means of differentiation between normal and malignant tissue. We examined qualitatively and semi-quantitatively the immunohistochemical expression of trypsin and TATI on paraffin-embedded serial tissue sections from 91 colorectal adenocarcinomas. The reverse-transcriptase-polymerase-chain reaction (RT-PCR) was also performed on fresh malignant tissue from 55 of the above adenocarcinomas. Normal and non-malignant tissues adjacent to the tumours were also evaluated. Cytoplasmic expression of trypsin (more than 25% of the cancer cells positive) was found in 67 (73.6%) adenocarcinomas, whereas TATI was expressed in the cytoplasm of 59 (64.8%) cases studied. Statistical analysis using Spearman's test has demonstrated a significant correlation between trypsin and TATI immunohistochemical expression (p<0.01). RT-PCR showed co-expression of trypsin and TATI mRNA in all carcinomas studied. Distinct patterns of trypsin and TATI immunohistochemical expression were observed in adjacent, non-malignant tissues, where both trypsin and TATI mRNA were also detected. Normal tissues were negative by immunohistochemistry. Our results indicate co-expression of trypsin and TATI in colorectal tumours both at the mRNA and protein level. We conclude that in colorectal neoplasms, high levels of trypsin and TATI may be important for malignant tumour formation and/or metastatic process.
胰蛋白酶及其特异性抑制剂TATI(肿瘤相关胰蛋白酶抑制剂)在正常人体胰腺和多种肿瘤中均有表达。本研究旨在评估胰蛋白酶和TATI在结直肠癌中的平行表达情况,并与它们在正常上皮组织中的表达作比较,因为蛋白酶及其抑制剂被认为在恶性肿瘤中是共同表达的。我们还评估了它们的表达作为区分正常组织和恶性组织的一种手段的可能意义。我们对91例结直肠腺癌石蜡包埋连续组织切片上胰蛋白酶和TATI的免疫组化表达进行了定性和半定量检查。对上述55例腺癌的新鲜恶性组织也进行了逆转录聚合酶链反应(RT-PCR)。还评估了肿瘤旁的正常和非恶性组织。在67例(73.6%)腺癌中发现胰蛋白酶的细胞质表达(超过25%的癌细胞呈阳性),而在所研究的59例(64.8%)病例中TATI在细胞质中表达。使用Spearman检验的统计分析表明胰蛋白酶和TATI免疫组化表达之间存在显著相关性(p<0.01)。RT-PCR显示在所研究的所有癌中胰蛋白酶和TATI mRNA共同表达。在相邻的非恶性组织中观察到胰蛋白酶和TATI免疫组化表达的不同模式,在这些组织中也检测到了胰蛋白酶和TATI mRNA。正常组织免疫组化呈阴性。我们的结果表明胰蛋白酶和TATI在结直肠肿瘤的mRNA和蛋白质水平上均共同表达。我们得出结论,在结直肠肿瘤中,高水平的胰蛋白酶和TATI可能对恶性肿瘤的形成和/或转移过程很重要。