title: Pepsinogen C is a new prognostic marker in primary breast cancer.
abstract: OBJECTIVE
  Here we evaluate in breast cancer patients the prognostic value of pepsinogen C, a proteolytic enzyme involved in the digestion of proteins in the stomach that is also synthesized by a significant percentage of breast carcinomas.
  
  
  METHODS
  Pepsinogen C expression was examined by immunoperoxidase staining in a series of 243 breast cancer tissue sections, and results obtained were quantified using the HSCORE system, which considers both the intensity and the percentage of cells staining at each intensity. Evaluation of the prognostic value of pepsinogen C was performed retrospectively in corresponding patients by multivariate analysis that took into account conventional prognostic factors. The mean follow-up period was 48.5 months.
  
  
  RESULTS
  A total of 113 carcinomas (46.5%) stained positively for this proteinase, but there were clear differences among them with regard to the intensity and percentage of stained cells. Pepsinogen C values were significantly 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)-positive tumors and ER-negative tumors (85.9 v 41.2, respectively; P < .05). Moreover, results indicated that low pepsinogen C content predicted shorter relapse-free survival duration and overall survival duration (P < .0001). Separate Cox multivariate analysis for relapse-free survival 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-positive patients (P < .0001 for both) and node-negative patients (P < .005 and P < .01, respectively).
  
  
  CONCLUSIONS
  Pepsinogen C is a new prognostic factor for early recurrence and death in both node-positive and node-negative breast cancer. In addition, and in contrast to most studies that concern the prognostic significance of proteolytic enzymes in cancer, pepsinogen C production by breast cancer cells is associated with lesions of favorable evolution.
authors.affiliation: Servicio de Cirugía General and Anatomía Patológica, Hospital de Jove, Gijón, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Vizoso
authors.forename: L M
authors.initials: LM
authors.lastname: Sánchez
authors.forename: I
authors.initials: I
authors.lastname: Díez-Itza
authors.forename: A M
authors.initials: AM
authors.lastname: Merino
authors.forename: C
authors.initials: C
authors.lastname: López-Otín
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D010435:Pepsinogens / Q000032:analysis*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D010435:Pepsinogens