Immunoenzymatically determined pepsinogen C concentration in breast tumor cytosols: An independent favorable prognostic factor in node-positive patients

The aim of this study was to determine the concentration and to evaluate th e prognostic value of pepsinogen C (PepC) in breast cancer patients. PepC i s an aspartic proteinase that is involved in the digestion of proteins in t he stomach and is also synthesized by a subset of human breast tumors. PepC concentrations were measured with a highly sensitive immunofluorometric as say, which uses two monoclonal antibodies that are specific for PepC and ha s 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 ev aluated. An optimal cutoff value, equal to 1.75 ng/mg of extracted protein, was first defined by statistical analysis, PepC status was then compared w ith other established prognostic factors, in terms of disease-free survival (DFS) and overall survival (OS), High PepC concentrations were found in sm all (P = 0.003) and well-differentiated tumors (P = 0.042) as well as in st age I (P = 0.003) and node-negative patients (P = 0.040), Statistically sig nificant associations of PepC concentration with patient age and estrogen r eceptor and progesterone receptor status were not observed. In univariate C ox regression analysis of the entire cohort of patients, negative PepC prov ed 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 statu s indicated that PepC status was a strong predictor of DFS (r = 0.0039) and the strongest factor for predicting OS (P = 0.0046) in node-positive but n ot in node-negative patients. Our results suggest that PepC may be used as an independent favorable prognostic factor in node-positive breast cancer p atients because there were no significant associations between PepC and the other prognostic factors evaluated in this group of patients.