Neuropilin-2 Expression in Normal Tissues, Various Tumors, and Primary and Metastatic Melanomas
EC Rushing, MJ Keefe, S Khanna, AA Jungbluth, KJ Busam, RM Alani. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Cleveland Clinic, Cleveland, OH; Johns Hopkins University School of Medicine, Baltimore, MD; Ludwig Institute for Cancer Research, New York, NY; Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Neuropilin-2 (NRP2) is a cell surface receptor involved in angiogenesis and axonal guidance. It has recently been shown to be a critical mediator of tumor-associated lymphangiogenesis and blocking of NRP2 function in vivo was demonstrated to inhibit tumor cell metastasis. Melanomas are notorious for their ability to metastasize at a relatively early stage of development and lymphangiogenesis is implicated as a metastasis conduit. Since NRP2 expression is not well documented, we investigated NRP2 expression in normal tissues, various tumors and melanomas.
Design: We evaluated NRP2 expression in 62 independent cases of melanoma in order to determine expression patterns across primary and metastatic melanomas as well as different histologic melanoma variants. We also evaluated a panel of normal human tissues and select non-melanocytic tumors since these have not been broadly evaluated for NRP2 expression. NRP2 expression was assessed using immunohistochemical staining with a polyclonal antibody against NRP2 and evaluated for extent and intensity of staining by two independent readers. Further analysis was performed on scanned slides using the FRIDA image analysis software.
Results: Significant staining was noted in all melanoma subtypes evaluated with 60/62 cases staining positively for NRP2. Among the cases of melanomas evaluated, all tumors demonstrated moderate to high levels of NRP2 expression with the exception of desmoplastic melanomas and some spindle cell nodular melanomas. All melanomas demonstrated significantly higher expression of NRP2 versus other tumor types evaluated (p<0.0001), with the exception of renal cell carcinomas which were highly positive for NRP2 expression as were normal kidneys.
Conclusions: We conclude that melanomas express high levels of NRP2 which is significantly elevated relative to all other malignancies evaluated in this study, with the exception of renal cell carcinomas. NRP2 was highly expressed in the majority of melanomas excluding desmoplastic variants and may be useful in the diagnosis of disseminated disease or as a prognostic indicator.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 41, Wednesday Morning