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Immunoenzymatically Determined Pepsinogen C Concentration in Breast Tumor Cytosols: An Independent Favorable Prognostic Factor in Node-positive Patients¹

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5G 1X5 and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5G 1L5 [A. S., E. P. D., M. A. L.]; Diagnostic Systems Laboratories Canada Inc., Toronto, Ontario, Canada M5G 1X5 [A. P-D., M. J. K.]; Department of Gynecologic Oncology, University of Turin, Turin, Italy 10121 [M. G., R. P., R. R., P. S.]; and Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Oviedo, Oviedo, Spain 33006 [C. L-O.]

The aim of this study was to determine the concentration and to evaluate the prognostic value of pepsinogen C (PepC) in breast cancer patients. PepC is an aspartic proteinase that is involved in the digestion of proteins in the stomach and is also synthesized by a subset of human breast tumors. PepC concentrations were measured with a highly sensitive immunofluorometric assay, which uses two monoclonal antibodies that are specific for PepC and has a detection limit of 0.1 ng/ml. Breast tumor cytosols from 151 patients (median follow-up, 67 months), stratified according to nodal status, were evaluated. An optimal cutoff value, equal to 1.75 ng/mg of extracted protein, was first defined by statistical analysis. PepC status was then compared with other established prognostic factors, in terms of disease-free survival (DFS) and overall survival (OS). High PepC concentrations were found in small (P = 0.003) and well-differentiated tumors (P = 0.042) as well as in stage I (P = 0.003) and node-negative patients (P = 0.040). Statistically significant associations of PepC concentration with patient age and estrogen receptor and progesterone receptor status were not observed. In univariate Cox regression analysis of the entire cohort of patients, negative PepC proved to be a significant predictor of reduced DFS (P = 0.0086) and OS (P = 0.025). Multivariate analysis in subgroups of patients defined by nodal status indicated that PepC status was a strong predictor of DFS (P = 0.0039) and the strongest factor for predicting OS (P = 0.0046) in node-positive but not in node-negative patients. Our results suggest that PepC may be used as an independent favorable prognostic factor in node-positive breast cancer patients because there were no significant associations between PepC and the other prognostic factors evaluated in this group of patients.

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