Immunohistochemical and clinicopathological correlation of the metastasis-associated gene 1 (MTA1) expression in benign and malignant pancreatic endocrine tumors

Pancreatic endocrine tumors are rare tumors with unpredictable clinical behavior. No histological features or immunohistochemical markers reliably predict malignant progression and the molecular basis of progression of pancreatic endocrine tumors remains unknown. The metastasis-associated gene 1 is thought to play a role in transcription repression and estrogen receptor interaction and is overexpressed in several human cancers, including endocrine neoplasms. The purpose of this study was to analyze the expression of metastasis-associated gene 1 in pancreatic endocrine tumors for its possible role in malignant progression. Twenty-seven pancreatic endocrine tumors were identified from our archive. The mean age at presentation was 57 years (range 28-86); the male/female ratio was 1.25 to 1, and the mean size was 4.5 cm (0.1-18 cm). The clinical follow-up data were examined and tumors were classified according to the 2004 World Health Organization criteria as benign behavior (WHO 1.1), uncertain behavior (WHO 1.2), well-differentiated endocrine carcinoma (WHO 2), and poorly differentiated endocrine carcinoma (WHO 3). Histopathological and immunohistochemical stains were evaluated and metastasis-associated gene 1 expression scored semiquantitatively as absent (1+), weak (2+), moderate (3+), or strong (4+). Statistical analysis was performed using Kruskal-Wallis nonparametric analysis of variance with a significance level of 0.05. Metastasis-associated gene 1 expression was significantly higher in malignant tumors (n = 17) with a mean staining intensity of 3.8 compared with 2.9 in benign tumors (n = 10, P = 0.046). The expression levels were significantly associated with WHO class (P = 0.028), as well as size of tumor (P = 0.029), and mitotic rate (P = 0.035). Metastasis-associated gene 1 expression was associated with local invasion with borderline significance (0.062). We show that metastasis-associated gene 1 expression is significantly associated with malignant behavior in pancreatic endocrine tumors. This may suggest a potential role for metastasis-associated gene 1 in the malignant progression and metastasis and its use as biomarker for malignant pancreatic endocrine tumors. Modern Pathology (2009) 22, 933-939; doi: 10.1038/modpathol.2009.50; published online 17 April 2009