The aim of this study is to provide a long-term follow-up of patients with tubular carcinoma and to investigate whether the separation of the mixed type of tubular carcinoma, tubular component more than 75%, from invasive ductal carcinoma with a major tubular component (ductal carcinoma MTC), tubular component 50 to 75%, is supported by long term follow-up. For this study 388 consecutive breast carcinomas were selected from the files of the Department of Pathology, Bispebjerg Hospital, Denmark for the years: 1956-59. Twenty tubular carcinomas were found and 16 ductal carcinomas MTC were also identified. For each patient with tubular carcinoma and ductal carcinoma MTC, two controls with ductal carcinoma NOS were selected. The patients in these four groups were followed until 1 April 1982. None of the patients were lost to follow-up. Among the 20 patients with tubular carcinoma, 10 died within this period compared to 37 of the 40 controls. Of the 16 patients with ductal carcinoma MTC, 15 died compared to 29 of the 32 controls. The difference in Kaplan-Meier survival curves between the tubular carcinomas and their controls is highly significant. There is no significant difference between ductal carcinomas MTC and their controls. These findings are not changed significantly when 5, 10, and 20 year survival rates are corrected for expected survival. This study demonstrates long-term survival for patients with tubular carcinoma as compared to ductal carcinoma NOS. There is no difference in long-term survival between ductal carcinoma MTC, tubular component between 50 and 75%, and ductal carcinoma NOS. It therefore seems appropriate to set 75% tubular component as a reasonable cut-off point for the mixed type of tubular carcinoma.

S U M M A R YCathepsin B is a lysosomal cysteine proteinase that may participate in cancer progression. We compared localization of its protein and activity during progression of human colorectal cancer. In adenomas and carcinomas, protein expression and, particularly, activity were elevated compared with those in normal colorectal mucosa. In normal mucosa, cathepsin B protein expression was moderate in stroma and variable in epithelium, whereas activity was mainly present in distinct areas of stroma directly underneath the surface of the colon and in epithelium at the surface of the colon. Stroma in adenomas and carcinomas contained moderate to high protein levels but little activity except for areas of angiogenesis, inflammation, and necrosis, in which activity was high. In adenomas and the majority of well-differentiated carcinomas and moderately differentiated carcinomas, cathepsin B protein and activity were found in granular form in the epithelium, close to the basement membrane. Protein and activity levels were low and diffusely distributed in cancer cells in the remainder of the well-differentiated and moderately differentiated carcinomas and in all poorly differentiated carcinomas. Invasive fronts in most cancers contained moderate protein levels but high activity. We conclude that (a) activity localization is essential to understand the role of cathepsin B in cancer progression, and (b) cathepsin B activity in human colon is associated with invasion of cancer cells, endothelial cells, and inflammatory cells, and in cell death, both apoptotic and necrotic.

Abstract-Decreased intracellular SOD protein levels and activity have been related with malignancy in the past. To investigate their relevance in the carcinogenetic process in the colon, we determined quantitatively CuZn-SOD and Mn-SOD levels and total SOD activity by histochemical means in human normal colorectal mucosa, adenomas, and carcinomas. Protein levels and activity were significantly decreased in carcinomas. CuZn-SOD protein levels, but not Mn-SOD levels or total SOD activity were related with differentiation grade and to a lesser extent with Dukes stage. Moderately differentiated carcinomas and Dukes stage A carcinomas showed lowest levels. Some carcinomas expressed elevated levels of CuZn-SOD and this was an indication of poor survival. It is concluded that decreased SOD expression is not a prognostic marker and seems to be a secondary phenomenon rather than directly linked with the carcinogenetic process. ᭧ 1997 Elsevier Science Inc.