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Polypeptide N-acetylgalactosaminyltransferase 6 expression in pancreatic cancer is an independent prognostic factor indicating better overall survival.

Li Z, Yamada S, Inenaga S, Imamura T, Wu Y, Wang KY, Shimajiri S, Nakano R, Izumi H, Kohno K, Sasaguri Y - Br. J. Cancer (2011)

Bottom Line: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively.The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features.Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

ABSTRACT

Background: The family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) is responsible for the altered glycosylation in cancer. The purpose of our study was to investigate the clinical significance of two isoforms, GalNAc-T6 and -T3, and their correlation with the prognosis of pancreatic cancer.

Methods: Immunohistochemistry was used to analyse GalNAc-T6 and -T3 expressions in 70 clinicopathologically characterised pancreatic cancer cases.

Results: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively. A close relationship was noted between GalNAc-T6 positive expression and pathological well/moderate differentiated type (P=0.001), small tumour size (P=0.044), absence of vascular invasion (P=0.009), and low stage of the American Joint Committee on Cancer systems (P=0.043). The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features. Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356).

Conclusion: Both GalNAc-T6 and -T3 expressions correlated significantly with tumour differentiation, whereas only GalNAc-T6 expression predicted prognosis in pancreatic cancer.

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Immunohistochemical analysis of GalNAc-T3 (1 : 3000 dilution) and GalNAc-T6 (1 : 1000 dilution) in human pancreatic cancers and normal ductal specimens ( × 100; inset, × 400). Bar, 100 μm. Normal pancreatic duct was positive for GalNAc-T3 (A), but negative for GalNAc-T6 (B). Well and moderately differentiated pancreatic cancers stain positively with GalNAc-T3 (C and E) and GalNAc-T6 (D and F), respectively. However, poorly differentiated cancer shows negative staining with both GalNAc-T3 (G) and GalNAc-T6 (H).
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fig2: Immunohistochemical analysis of GalNAc-T3 (1 : 3000 dilution) and GalNAc-T6 (1 : 1000 dilution) in human pancreatic cancers and normal ductal specimens ( × 100; inset, × 400). Bar, 100 μm. Normal pancreatic duct was positive for GalNAc-T3 (A), but negative for GalNAc-T6 (B). Well and moderately differentiated pancreatic cancers stain positively with GalNAc-T3 (C and E) and GalNAc-T6 (D and F), respectively. However, poorly differentiated cancer shows negative staining with both GalNAc-T3 (G) and GalNAc-T6 (H).

Mentions: The specificity of the GalNAc-T6 polyclonal antibody was tested by immunohistochemistry and western blotting. After incubation of this antibody with the excess of synthesised peptides of GalNAc-T6, the positive immunostaining was completely abolished (Figure 1). Immunohistochemically, GalNAc-T3 and -T6 showed only cytoplasmic expressions (Figure 2). The expression of GalNAc-T3 was present in most of the normal ductal epithelium samples (Figure 2A), whereas GalNAc-T6 expression was rare or very weakly detectable (Figure 2B). The expression of GalNAc-T3 was present in 54 of 70 (77%) pancreatic adenocarcinoma specimens: 38%, weak; 23%, moderate; and 16%, strong, respectively. The expression of GalNAc-T6 was present in 36 of 70 (51%) specimens: 34%, weak; 13%, moderate; and 4%, strong, respectively. When GalNAc-Ts expression was dichotomised into groups of either positive (weak to strong staining) or negative, the GalNAc-T3/-T6 immunoprofile was 19%, (−)/(−); 30%, (+)/(−); 4%, (−)/(+); and 47%, (+)/(+), respectively.


Polypeptide N-acetylgalactosaminyltransferase 6 expression in pancreatic cancer is an independent prognostic factor indicating better overall survival.

Li Z, Yamada S, Inenaga S, Imamura T, Wu Y, Wang KY, Shimajiri S, Nakano R, Izumi H, Kohno K, Sasaguri Y - Br. J. Cancer (2011)

Immunohistochemical analysis of GalNAc-T3 (1 : 3000 dilution) and GalNAc-T6 (1 : 1000 dilution) in human pancreatic cancers and normal ductal specimens ( × 100; inset, × 400). Bar, 100 μm. Normal pancreatic duct was positive for GalNAc-T3 (A), but negative for GalNAc-T6 (B). Well and moderately differentiated pancreatic cancers stain positively with GalNAc-T3 (C and E) and GalNAc-T6 (D and F), respectively. However, poorly differentiated cancer shows negative staining with both GalNAc-T3 (G) and GalNAc-T6 (H).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111199&req=5

fig2: Immunohistochemical analysis of GalNAc-T3 (1 : 3000 dilution) and GalNAc-T6 (1 : 1000 dilution) in human pancreatic cancers and normal ductal specimens ( × 100; inset, × 400). Bar, 100 μm. Normal pancreatic duct was positive for GalNAc-T3 (A), but negative for GalNAc-T6 (B). Well and moderately differentiated pancreatic cancers stain positively with GalNAc-T3 (C and E) and GalNAc-T6 (D and F), respectively. However, poorly differentiated cancer shows negative staining with both GalNAc-T3 (G) and GalNAc-T6 (H).
Mentions: The specificity of the GalNAc-T6 polyclonal antibody was tested by immunohistochemistry and western blotting. After incubation of this antibody with the excess of synthesised peptides of GalNAc-T6, the positive immunostaining was completely abolished (Figure 1). Immunohistochemically, GalNAc-T3 and -T6 showed only cytoplasmic expressions (Figure 2). The expression of GalNAc-T3 was present in most of the normal ductal epithelium samples (Figure 2A), whereas GalNAc-T6 expression was rare or very weakly detectable (Figure 2B). The expression of GalNAc-T3 was present in 54 of 70 (77%) pancreatic adenocarcinoma specimens: 38%, weak; 23%, moderate; and 16%, strong, respectively. The expression of GalNAc-T6 was present in 36 of 70 (51%) specimens: 34%, weak; 13%, moderate; and 4%, strong, respectively. When GalNAc-Ts expression was dichotomised into groups of either positive (weak to strong staining) or negative, the GalNAc-T3/-T6 immunoprofile was 19%, (−)/(−); 30%, (+)/(−); 4%, (−)/(+); and 47%, (+)/(+), respectively.

Bottom Line: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively.The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features.Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

ABSTRACT

Background: The family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) is responsible for the altered glycosylation in cancer. The purpose of our study was to investigate the clinical significance of two isoforms, GalNAc-T6 and -T3, and their correlation with the prognosis of pancreatic cancer.

Methods: Immunohistochemistry was used to analyse GalNAc-T6 and -T3 expressions in 70 clinicopathologically characterised pancreatic cancer cases.

Results: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively. A close relationship was noted between GalNAc-T6 positive expression and pathological well/moderate differentiated type (P=0.001), small tumour size (P=0.044), absence of vascular invasion (P=0.009), and low stage of the American Joint Committee on Cancer systems (P=0.043). The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features. Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356).

Conclusion: Both GalNAc-T6 and -T3 expressions correlated significantly with tumour differentiation, whereas only GalNAc-T6 expression predicted prognosis in pancreatic cancer.

Show MeSH
Related in: MedlinePlus