Published online before print July 16, 2009

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(American Journal of Pathology. 2009;175:479-488.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.090024

Increased Immunoreactivity to SLIT/ROBO1 in Ovarian Endometriomas

A Likely Constituent Biomarker for Recurrence

Fanghua Shen^*, Xishi Liu^*, Jian-Guo Geng and Sun-Wei Guo

From the Shanghai OB/GYN Hospital,^* Fudan University, Shanghai, China; the Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; the Vascular Biology Center and Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota; Renji Hospital and the Institute of Obstetric and Gynecologic Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China

While surgery is currently the treatment of choice for endometriosis, recurrence remains a serious problem, and its prevention is an unmet clinical need. SLIT, a secreted protein that functions through the Roundabout (ROBO) receptor as a repellent for axon guidance and neuronal migration, has been recently found to induce tumor angiogenesis. We investigated the potential role of SLIT/ROBO1 in ovarian endometriomas and examined their predictive value in recurrence based on tissue samples from 43 patients with recurrence and 45 without recurrence. Microvascular density counts were evaluated by CD34 immunohistochemistry, and statistical analyses were performed to evaluate the effect of SLIT/Robo1 on recurrence risk after adjustment for other risk factors. We found that SLIT expression was positively correlated with microvascular density in ectopic endometrium and that its expression was higher in ectopic endometrium than control endometrium. Both SLIT and Robo1 expression were higher in recurrent cases than in non-recurrent cases. Higher immunoreactivity to SLIT, along with the presence of adhesion, PR-B, and nuclear factor-B, was identified to be a risk factor for recurrence, with a sensitivity of 86% and a specificity of 87%. Therefore, increased SLIT immunoreactivity is likely an important constituent factor for recurrence of ovarian endometriomas, possibly through promoting angiogenesis in ectopic endometrium. Thus, the SLIT/ROBO1 system may be a potential target for reducing the risk of recurrence.