An abnormally high expression of ISL-1 represents a potential prognostic factor in gastric cancer

• Published in: Human pathology 2015-09, Vol.46 (9), p.1282-1289
• Main Authors: Guo, Chen, MS, Wang, Weiping, PhD, Shi, Qiong, BS, Chen, Ping, BS, Zhou, Chunyan, MD, PhD
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma - secondary; Adult; Aged; Aged, 80 and over; Animals; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Chi-Square Distribution; Committees; Confidence intervals; Female; Gastric cancer; Humans; Immunohistochemistry; ISL-1; Kaplan-Meier Estimate; Laboratory animals; LIM-Homeodomain Proteins - genetics; LIM-Homeodomain Proteins - metabolism; Lymphatic Metastasis; Lymphatic system; Male; Medical prognosis; Metastasis; Mice; Mice, Nude; Middle Aged; Mortality; Multivariate Analysis; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; NIH 3T3 Cells; Odds Ratio; Overall survival; Pathology; Prognostic biomarker; Proportional Hazards Models; Proteins; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Studies; Time Factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transfection; Tumor Burden; Up-Regulation
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2015.05.006

Summary Insulin gene enhancer binding protein–1 (ISL-1) is a transcription factor involved in development of the heart, motor neurons, and pancreas. Our previous study indicated that ISL-1 was overexpressed in gastric cancer but not in other gastrointestinal tumors. However, no immunohistochemical or clinicopathological studies of ISL-1 in gastric carcinoma have been performed. The aim of this study was to determine the expression and prognostic value of ISL-1 in gastric carcinoma. A nude mouse xenograft model was established to study the role of ISL-1 on cancer genesis and development in vivo. Overexpression of ISL-1 significantly enhanced the tumorigenicity of NIH3T3 cells in vivo. ISL-1 expression was evaluated using immunohistochemistry in 456 human gastric carcinoma and normal tissues. ISL-1 was significantly overexpressed in gastric adenocarcinoma compared with normal gastric tissues. ISL-1 expression was significantly associated with depth of invasion, lymph node metastasis, TNM stage, and histological grade ( P < .05, χ2 test). Positive ISL-1 expression was associated with poorer 5-year overall survival in gastric cancer ( P = .001, log-rank test). Multivariate Cox regression analysis demonstrated that ISL-1 expression ( P = .047) could be an independent prognostic factor for overall survival in gastric carcinoma. This study suggests that ISL-1 may be a useful prognostic biomarker and may represent a novel therapeutic target for gastric adenocarcinoma.