Expression of pepsinogen C in gynecomastias and male breast carcinomas

Pepsinogen C is a proteolytic enzyme involved in the digestion of proteins in the stomach; it is also synthesized by a significant percentage of femal e breast carcinomas. In addition, it has been demonstrated that pepsinogen C is one of the few proteins induced by androgens in breast carcinoma cells . Here we evaluate the expression of pepsinogen C by immunoperoxidase stain ing in normal breast tissue from 3 male patients, 15 gynecomastia tissues, 2 male in situ breast carcinomas, and 68 male invasive breast carcinomas. P epsinogen C immunostaining values were quantified in male breast tumors usi ng the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity, The results indicated positive immuno histochemical staining for pepsinogen C in all gynecomastia tissues, the tw o in situ ductal carcinomas, and 52 of 68 invasive breast carcinomas (76.4% ). The three normal breast tissues analyzed showed negative staining for pe psinogen C, whereas invasive tumors showed clear differences among them wit h regard to the intensity and percentage of staining cells, In addition, pe psinogen C scores were significantly higher in well-differentiated (grade I , 188.7) and moderately differentiated (grade II, 145.8) tumors than in poo rly differentiated (grade III, 98.5) tumors (p = 0.032). Similarly, signifi cant differences in pepsinogen C content were found between estrogen recept or (ER)-positive tumors and ER-negative tumors (158.5 vs. 44.3, respectivel y; p = 0.009). Patients with pepsinogen C-positive tumors reached longer re lapse-free and overall survival periods than did those with tumors with neg ative staining, but no statistical differences were observed between surviv al curves calculated for these two groups of patients. This results demonst rate expression of pepsinogen C by gynecomastias and by a high percentage o f male breast carcinomas and may indicate an important role of pepsinogen C in the pathophysiology of male breast diseases.