The co-expression of functional gastric proteins in dynamic gastric diseases and its clinical significance

Abstract

Background: Pepsinogen C (PGC) and mucin1 (MUC1) are important physiologically functional gastric proteins; Mucin2 (MUC2) is an "ectopic" functional protein in intestinal metaplasia of gastric mucosa. We analyzed the co-expression of the above-mentioned three proteins in dynamic gastric diseases {superficial gastritis (SG)-atrophic gastritis (AG)--gastric cancer (GC)} as well as different histological types of gastric cancer in order to find molecular phenotypes of gastric cancer and precancerous disease and further explore the potential co-function of PGC, MUC1 and MUC2 in the occurrence and development of gastric cancer.

Methods: The SG-AG-GC sequence was 57-57-70 cases in this case-control study, respectively. Different histological types of GC were 28 cases of highly and moderately differentiated aden ocarcinoma (HMDA)、30 of poorly differentiated adenocarcinoma (PDA) and 12 of mucinous adenocarcinoma (MA) or signet ring cell carcinoma (SRCC). PGC, MUC1 and MUC2 expression in situ were detected in all 184 cases using immunohistochemistry.

Results: Both PGC and MUC1 had a significantly decreased expression in GC than in SG and AG (P < 0.0001 and P < 0.01, respectively); While MUC2 had a significant increased expression in AG than in SG and GC (P < 0.0001). Seven phenotypes of PGC, MUC1 and MUC2 co-expression were found in which PGC+/MUC1+/MUC2- phenotype took 94.7%(54/57) in SG group; PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+ phenotype took 43.9% (25/57) and 52.6% (30/57) in AG; the phenotypes in GC group appeared variable; extraordinarily, PGC-/MUC1-/MUC2+ phenotype took 100% (6/6) in MA or SRCC group and had a statistical significance compared with others (P < 0.05).

Conclusions: Phenotypes of PGC, MUC1 and MUC2 co-expression in dynamic gastric diseases are variable. In SG group it always showed PGC+/MUC1+/MUC2- phenotype and AG group showed two phenotypes (PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+); the phenotypes in GC group appeared variable but the phenotype of PGC-/MUC1-/MUC2+ may be a predictive biomarker for diagnosing MA or SRCC, or distinguishing histological MA or SRCC from tubular adenocarcinoma accompanied by mucinous secretion or signet ring cell scattered distribution.

Figure 1

The expression of PGC, MUC1, MUC2 proteins in different gastric mucosa tissues (× 200). A. strong positive expression of PGC in the gastric mucosa of superficial gastritis (SG) group; B. positive expression of PGC in atrophic gastritis (AG) group, a few negative expression; C. negative expression of PGC in moderately differentiated adenocarcinoma (MDA) group; D. negative expression of PGC in signet ring cell carcinoma (SRCC) group. E. strong positive expression of MUC1 in SG group; F. positive expression of MUC1 in AG group; G. positive expression of MUC1 in poorly differentiated adenocarcinoma (PDA) group; H. negative expression of MUC1 in SRCC group; I. negative expression of MUC2 in SG group; J. strong positive expression of MUC2 in AG group; K. positive expression of MUC2 in PDA group; L. strong positive expression of MUC2 in mucinous adenocarcinoma group. The arrow all means the cells of pathological changes.

Figure 2

The phenotype of PGC/MUC1/MUC2 co-expression in the same pathological changes (× 200). A. The negative expression of PGC in moderately differentiated adenocarcinoma (MDA) group. B. The positive expression of MUC1 in MDA group. C. The positive expression of MUC2 in MDA group. D. The negative expression of PGC in poorly differentiated adenocarcinoma (PDA) group. E. The positive expression of MUC1 in PDA group. F. The negative expression of MUC2 in PDA group. G. The negative expression of PGC in signet ring cell carcinoma (SRCC) group. H. The negative expression of MUC1 in SRCC group. I. The positive expression of MUC2 in SRCC group. Every three figures in a horizontal composition were all from the same individual. The arrow all means the cells of pathological changes.