Elsevier

Surgery

Volume 141, Issue 1, January 2007, Pages 41-50
Surgery

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

https://doi.org/10.1016/j.surg.2006.05.009Get rights and content

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.

Section snippets

Patients and specimens

After Institutional Review Board approval, paraffin-embedded tissue from 131 patients who had gastric adenocarcinoma resected at Johns Hopkins University Hospital between 1985 and 1995 was evaluated retrospectively. The archived tissue from these patients had been constructed previously into 7 TMA blocks by the Johns Hopkins University Department of Pathology. The TMAs contained 3 to 8 tissue samples from each patient, for a total of 663 cores. Each sample consisted of a 1.5-mm diameter core

Increased expression of prothymosin-α in gastric adenocarcinoma lesions

We evaluated prothymosin-α expression in gastric samples by staining the seven tissue arrays constructed at Johns Hopkins with a monoclonal antibody against prothymosin-α and horseradish peroxidase histochemistry. Normal gastric mucosa samples showed the strongest nuclear prothymosin-α staining predominantly in cells in the gland neck (epithelial progenitor zone) and in surface mucous cells. Cells of the deep gland including chief and parietal cells were generally negative (Fig 1A). In

Discussion

Gastric cancer is a major cause of worldwide cancer mortality, yet the factors influencing the biologic behavior of this tumor remain poorly understood. Discovery of new biomarkers for this disease may yield important insights into the biology of this disease and could prove useful for both early detection and the development of new therapies. Studies in mouse models have yielded several potential biomarkers for gastric preneoplasia and neoplasia,11, 13 however their role in human disease has

References (31)

  • V.C. Smith et al.

    Role of Helicobacter pylori gastritis in gastric atrophy, intestinal metaplasia and gastric neoplasia

    Microsc Res Tech

    (2000)
  • M.I. Filipe et al.

    Intestinal metaplasia types and the risk of gastric cancer: a cohort study in Slovenia

    Int J Cancer

    (1994)
  • E.J. Kuipers

    Exploring the link between Helicobacter pylori and gastric cancer

    Aliment Pharmacol Ther

    (1999)
  • P.H. Schmidt et al.

    Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma

    Lab Invest

    (1999)
  • A.M. Halldorsdottir et al.

    Spasmolytic polypeptide expressing metaplasia (SPEM) associated with gastric cancer in Iceland

    Dig Dis Sci

    (2003)
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    Supported by grants from Department of Veterans Affairs Merit Review Award, Vanderbilt SPORE in Gastrointestinal Cancer (1P 50 CA95103), the AGA Funderburg Award in Gastric Biology Related to Cancer, Discovery Grant from the Vanderbilt-Ingram Cancer Center, a Vanderbilt Clinical Oncology Research Career Development Program Fellowship (K12 CA090625), CA67108 from the National Cancer Institute, and Johns Hopkins SPORE in Gastrointestinal Cancer (P50 CA62924) from NCI.

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