Roundabout1 distribution in neoplastic and non-neoplastic diseases with a focus on neoangiogenesis

Slit and its receptor Roundabout (Robo) are important for neuronal development and neo-angiogenesis in various neoplastic and non-neoplastic diseases. Angiogenesis is a key factor for tumor growth and other angiogenesis-dependent diseases including rheumatoid arthritis, and chronic inflammation Recently, over-expression of Slit/Robo1 family proteins has been reported in several types of malignancy. We explored the expression of Robo1 in neoplastic and non-neoplastic diseases with a focus on newly formed blood vessels. Three hundred and thirty four cases of malignancy and forty five cases of angiogenic diseases were recruited. Using the A7241A Robo1 monoclonal antibody, Robo1 expression was validated by immunohistochemistry. Among malignant cases, endothelial cells of newly formed blood vessels in 283 tumors (84.7%) exhibited positive staining with above antibody. In non-neoplastic diseases, newly formed blood vessels were positive in 70.6% (12/17) cases of chronic inflammation, 100% (18/18) cases of pyogenic granuloma and 83.3% (5/6) cases of rheumatoid arthritis. Recently, newly anti-angiogenesis therapy is drawing attention as effective therapy for angiogenesis-dependent diseases without regard to their neoplastic or non-neoplastic nature. Our results showed a large number of neoplastic and non-neoplastic diseases showed positive staining for ROBO1 by immunohistochemistry. Thus, Robo1 targeted therapy may create new strategies for the treatment of angiogenic-dependent diseases through the suppression of angiogenesis. Further, besides the majority of liver cell carcinomas (23/28, 82.1%), Robo1 was positive in 100% of the squamous cell carcinoma of the esophagus, uterine cervix, lung and skin. Thus, immunohistochemical evaluation of Robo1 may be useful as an additional diagnostic tool for liver cell carcinomas and squamous cell carcinomas.