Expression and prognostic significance of prothymosin-alpha and ERp57 in human gastric cancer.
OBJECTIVE
Prothymosin-alpha 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-alpha 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-alpha 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-alpha 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.
Leys
Charles M
CM
Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232-2733, USA.
Nomura
Sachiyo
S
LaFleur
Bonnie J
BJ
Ferrone
Soldano
S
Kaminishi
Michio
M
Montgomery
Elizabeth
E
Goldenring
James R
JR
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008679:Metaplasia / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D011379:Prognosis; D040081:Protein Array Analysis; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D012189:Retrospective Studies; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism
D014408:Biomarkers, Tumor; D018832:Molecular Chaperones; D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human