Surveillance colonoscopy and biopsy are inaccurate methods of predicting the likelihood of ulcerative colitis patients to develop colon carcinoma. We examined uPA and PAI-1 as potential markers for assessing these patients and those with familial polyposis who are at risk of developing colon cancer. For comparison, biopsies of normal colon and Crohn's disease were evaluated. We examined 77 colonic mucosa specimens taken from patients undergoing elective resection for benign and malignant colonic disease. uPA and PAI-1 were measured using a monoclonal antibody-based ELISA kit (American Diagnostica, Greenwich, CT) and expressed as ng/mg extract protein. Intra- and interassay controls of uPA gave CV = 3-4% and CV = 8-9%, respectively, while those for PAI-1 were 6-7% and 10-11%, respectively. The Mann-Whitney test showed that both uPA and PAI-1 expression were significantly higher in colon cancer, chronic ulcerative colitis, and Crohn's disease than in normal colon. uPA in familial polyposis samples was similar to that of normal colon, while PAI-1 was much lower than in normal colon. Neither patient age nor sex appeared to influence the expression of these potential markers in any tissue. The pattern of uPA and PAI-1 expression in normal, benign and malignant colon suggests these proteins deserve further consideration as markers for assessing colon carcinoma risk.

Further analyses are needed to determine which parameters are related to and possibly predictive of increased carcinoma risk.

Determination of the frequency and levels of EGF receptors, HER-2/neu protein, and cathepsin D in uteri with and without cancer and the availability of reference materials developed in our laboratory, will allow evaluation of their prognostic value in cancers of the uterus.

We evaluated cathepsin D concentrations in 318 breast carcinoma specimens with a standardized IRMA and established distribution values of 5.9-217.8 nmol/g (median 51.8). Concentrations of cathepsin D did not correlate with age or with concentrations of HER-2/neu oncoprotein, estrogen receptor, or epidermal growth factor receptors. A significant correlation was observed between cathepsin D and progestin receptor (P = 0.009), but only in postmenopausal patients. In our role as a National Reference Laboratory for conducting interlaboratory comparisons of tumor markers, we evaluated cathepsin D assay proficiency by using control samples with intra- and interassay CVs of 2-8% and 10-13%, respectively. Human reference specimens containing known quantities of cathepsin D were developed to facilitate standardized testing. The IRMA procedure and the use of quality-assurance samples permits evaluation of the clinical significance of cathepsin D in human breast cancer trials.

Overexpression of cathepsin D in several types of carcinoma in women appears to be associated with a poor clinical course. In this prospective investigation, cathepsin D levels in 170 specimens of normal and neoplastic human tissues were determined simultaneously by enzyme immunoassay (EIA) and immunoradiometric assay (IRMA) to allow comparisons in multicentric studies, such as cooperative clinical trials. Nonmalignant uteri and specially prepared reference powders were also evaluated. Linear regression analysis between the two assays for all specimens [EIA = 0.87(IRMA)-3.18] demonstrated a correlation coefficient (r) of 0.99 (P < 0.001). When malignancies were categorized by the tissue origin (i.e., breast, uterus, ovary, lymph node, and colon), highly significant correlations were also observed (regressions slopes ranged from 0.58 to 1.02). Intra- and interassay controls conducted for the new EIA procedure gave CV% ranging from 4.4 to 10.2, which was similar to the IRMA test for cathepsin D. The results of both assays correlated well and were highly reproducible. Either assay may be used with confidence that comparable cathepsin D values will be obtained in a wide range of tissue biopsies.