Expression and prognostic significance of prothymosin-α and ERp57 in human gastric cancer

• Published in: Surgery 2007, Vol.141 (1), p.41-50
• Main Authors: Leys, Charles M., MD, MSCI, Nomura, Sachiyo, MD, PhD, LaFleur, Bonnie J., PhD, Ferrone, Soldano, MD, PhD, Kaminishi, Michio, MD, PhD, Montgomery, Elizabeth, MD, Goldenring, James R., MD, PhD
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Biomarkers, Tumor - metabolism; Down-Regulation; Endoplasmic Reticulum - metabolism; Humans; Immunohistochemistry; Metaplasia - metabolism; Molecular Chaperones - metabolism; Prognosis; Protein Array Analysis; Protein Disulfide-Isomerases - metabolism; Protein Precursors - metabolism; Retrospective Studies; Stomach - metabolism; Stomach - pathology; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Surgery; Survival Rate; Thymosin - analogs & derivatives; Thymosin - metabolism
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2006.05.009

Purpose Prothymosin-α and ERp57 were previously identified as markers for gastric metaplasia in a mouse model of Helicobacter-induced gastric metaplasia and neoplasia. In this paper we assess whether the expression of these putative biomarkers in humans is correlated with gastric metaplasia and adenocarcinoma and clinical outcomes. Methods Eight tissue microarrays, containing 749 paraffin-embedded tissue cores from 164 gastric cancer patients, were stained for prothymosin-α and ERp57 by horseradish peroxidase immunohistochemical techniques. The proportion of stained cells per core was quantitated using the Ariol SL-50 automated image analysis system. Results Prothymosin-α stained a significantly higher percentage of nuclei in cancer and metastases compared with normal gastric mucosa. ERp57 staining was significantly decreased in cancer and metastases compared with both normal gastric mucosa and metaplasias. ERp57 expression also correlated with greater depth of tumor invasion and advanced stage of disease. Kaplan-Meier survival analysis determined that tumors with the highest quartile of ERp57 expression were statistically associated with longer postoperative survival. A Cox proportional hazard analysis showed that maintenance of ERp57 expression was associated with longer postoperative survival. Conclusions These results suggest that although prothymosin-α is overexpressed in gastric adenocarcinoma, it is not associated with alterations in survival. In contrast, loss of ERp57 expression correlated with more aggressive disease and could provide useful prognostic information for gastric cancer patients.