Regional variations of urokinase‐type plasminogen activator in human colorectal cancer: A quantitative study by image analysis

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Abstract
Qualitative histological studies in the distribution of urokinase-type plasminogen activator (uPA) in human colorectal carcinomas have been well documented. However, to our knowledge the histological distribution of this enzyme has not been quantified in any tumour. For the present image analysis study, uPA was demonstrated in sections of human colorectal cancer using immunoperoxidase technique. A total of 9 colorectal carcinoma cases were used, in which 132 regions were analysed. Within each region, staining intensity measurements were made at evenly spaced intervals. Samples of normal mucosa from 6 cases were also studied. Enzyme levels were assessed with staining intensity measurements. For each section, a negative control section was included, in which the primary antibody was omitted. Staining for uPA was quantified for each region in the test section, and the measurement for the corresponding region of the negative control was then subtracted. The enzyme uPA was localised more at the tumour edge than in the tumour centre or distant host tissue. These differences were highly significant (p < 0.0001). There was also a highly significant difference in staining intensity when tumour regions adjacent to pushing edge were compared with those adjacent to infiltrating edge (p < 0.0001). Infiltrating tumours showed stronger staining for uPA than tumours with pushing edges. Since invasive activity is thought to be maximal at the edge of the tumour, localisation of uPA at this site is consistent with the role of this enzyme in the process of tumour invasion.

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