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

Xu Q, Sun LP, Wang BG, Liu JW, Li P, He CY, Yuan Y - BMC Clin Pathol (2013)

Bottom Line: 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).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.

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Affiliation: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, North Nanjing Street 155#, Heping District, Shenyang 110001, People's Republic of China. yyuan@mail.cmu.edu.cn.

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.

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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.
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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.

Mentions: The co-expression characteristics of PGC, MUC1, MUC2 proteins were analyzed. We found the phenotype of PGC+/MUC1+/MUC2- accounted for 94.7% (54/57) in SG group; PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+ phenotype accounted for 43.9% (25/57) and 52.6% (30/57) in AG group, respectively. The phenotypes in GC group appeared variable, among them, all cases were PGC- phenotype, in which most were individuals with phenotype of PGC-/MUC1+/ MUC2+ or PGC-/MUC1+/MUC2- (33 or 26 cases, accounted for 47.1% and 37.1% respectively, as shown in Figure 2 A-C or D-F). Furthermore, the GC cases were classified according to histological types, we found that 100% (6/6) in the MA or SRCC group were the phenotype of PGC-/MUC1-/MUC2+ (Figure 2 G-I), other phenotypes group in the MA or SRCC group were significantly lower compared with that of PGC-/MUC1-/MUC2+ phenotype group (P < 0.05, Table 3).


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

Xu Q, Sun LP, Wang BG, Liu JW, Li P, He CY, Yuan Y - BMC Clin Pathol (2013)

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.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3750757&req=5

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.
Mentions: The co-expression characteristics of PGC, MUC1, MUC2 proteins were analyzed. We found the phenotype of PGC+/MUC1+/MUC2- accounted for 94.7% (54/57) in SG group; PGC+/MUC1+/MUC2+ and PGC-/MUC1+/MUC2+ phenotype accounted for 43.9% (25/57) and 52.6% (30/57) in AG group, respectively. The phenotypes in GC group appeared variable, among them, all cases were PGC- phenotype, in which most were individuals with phenotype of PGC-/MUC1+/ MUC2+ or PGC-/MUC1+/MUC2- (33 or 26 cases, accounted for 47.1% and 37.1% respectively, as shown in Figure 2 A-C or D-F). Furthermore, the GC cases were classified according to histological types, we found that 100% (6/6) in the MA or SRCC group were the phenotype of PGC-/MUC1-/MUC2+ (Figure 2 G-I), other phenotypes group in the MA or SRCC group were significantly lower compared with that of PGC-/MUC1-/MUC2+ phenotype group (P < 0.05, Table 3).

Bottom Line: 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).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, North Nanjing Street 155#, Heping District, Shenyang 110001, People's Republic of China. yyuan@mail.cmu.edu.cn.

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.

No MeSH data available.


Related in: MedlinePlus