PEPSINOGEN-C IS A NEW PROGNOSTIC MARKER IN PRIMARY BREAST-CANCER

Purpose: Here we evaluate in breast cancer patients the prognostic val ue of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant perc entage of breast carcinomas. Patients and Methods: Pepsinogen C expres sion was examined by immunoperoxidase staining in a series of 243 brea st cancer tissue sections, and results obtained were quantified using the HSCORE system, which considers both the intensity and the percenta ge of cells staining at each intensity. Evaluation of the prognostic v alue of pepsinogen C was performed retrospectively in corresponding pa tients by multivariate analysis that took into account conventional pr ognostic factors. The mean follow-up period was 48.5 months. Results: A total of 113 carcinomas (46.5%) stained positively for this proteina se, but there were clear differences among them with regard to the int ensity and percentage of stained cells. Pepsinogen C values were signi ficantly higher in well differentiated (grade I, 89.1) and moderately differentiated (grade II, 88.5) tumors than in poorly differentiated ( grade III, 27.7) tumors (P < .001). Similarly, significant differences in pepsinogen C content were found between estrogen receptor (ER) pos itive tumors and ER-negative tumors (85.9 v 41.2, respectively; P < .0 5), Moreover, results indicated that low pepsinogen C content predicte d shorter relapse-free survival duration and overall survival duration (P < .0001). Separate Cox multivariate analysis for relapse free surv ival and overall survival in subgroups of patients as defined by node status showed that pepsinogen C expression was the strongest factor to predict both relapse-free survival and overall survival in node-posit ive patients (P < .0001 for both) and node-negative patients (P < .005 and P < .01, respectively). Conclusion: Pepsinogen C is a new prognos tic factor for early recurrence and death in both node-positive and no de-negative breast cancer, In addition, and in contrast to most studie s that concern the prognostic significance of proteolytic enzymes in c ancer, pepsinogen C production by breast cancer cells is associated wi th lesions of favorable evolution.