Tissue microarray evaluation of prothymosin-α as a biomarker for human gastric metaplasia and neoplasia

Abstract

Introduction. Our objective was to determine if prothymosin-α, a marker for gastric metaplasia previously identified in a Helicobacter-induced gastric metaplasia and neoplasia mouse model, shows significant up regulation in human gastric metaplasia and neoplasia compared to the normal gastric mucosa. Methods. Seven tissue microarrays containing a total of 594 cores from 132 patients with gastric cancer were obtained. Each core represented a distinct pathology, including gastric cancer (275), spasmolytic polypeptide expressing metaplasia (SPEM, 15), intestinal metaplasia (19), normal gastric mucosa (107), duodenum (61), and lymph nodes metastases (117). Immunohistochemistry for prothymosin-α was performed and the staining was quantified using the BLISS automated slide scanner and TMAscore software package (Bacus Labs, Inc.). TFF2 immunostaining of serial tissue array sections was also performed to identify SPEM. Mean scores for prothymosin-α staining were analyzed using Student’s t-test with level of significance at P < 0.05. Results. Prothymosin-α antibodies strongly stained the nuclei in sections from intestinal-type gastric cancers. The mean percent immunohistochemistry area for prothymosin-alpha staining was 22.1 (SEM ± 1.0) in normal gastric mucosa, 23.1 (±1.8) in intestinal metaplasia, 24.9 (±2.2) in SPEM, and 27.6 (±1.0) in gastric cancer. Statistical analysis with Student’s t-test revealed a statistically significant increase in prothymosin-α staining in gastric cancer as compared to normal mucosa, with P value > 0.001. While staining was elevated in both SPEM and intestinal metaplasia compared with normal mucosa, neither comparison reached statistical significance. Conclusions. Prothymosin-α showed increased immunostaining in the progression from normal mucosa to metaplasia to gastric cancer. The results confirm findings in mice indicating up regulation of prothymosin-α in association with neoplastic transformation. These findings suggest that prothymosin-α may represent a useful biomarker to assist in the early diagnosis of gastric cancer.