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Cellular Oncology
Volume 31, Issue 6, Pages 423-436
http://dx.doi.org/10.3233/CLO-2009-0504

Co-Expression of Plexin-B1 and Met in Human Breast and Ovary Tumours Enhances the Risk of Progression

Guido Valente,1 Giuseppina Nicotra,1 Marisa Arrondini,1 Roberta Castino,2 Lorena Capparuccia,3 Maria Prat,4 Simonetta Kerim,5 Luca Tamagnone,5 and Ciro Isidoro2

1Pathology Section, Department of Clinical and Experimental Medicine, Amedeo Avogadro University, Novara, Italy
2Laboratory of Molecular Pathology, Department of Medical Sciences, Amedeo Avogadro University, Novara, Italy
3Institute for Cancer Research and Treatment (IRCC), University of Torino Medical School, Candiolo (TO), Italy
4Laboratory of Histology, Department of Medical Sciences, Amedeo Avogadro University, Novara, Italy
5Cytogenetics Unit, Department of Laboratory Diagnostics, San Giovanni Hospital, Torino, Italy

Copyright © 2009 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Plex-B1, the receptor of Sema4D, has been implicated in tumour growth, angiogenesis and metastasis. The binding of Sema4D to Plex-B1 can trigger the activation of Met tyrosine kinase, thereby promoting cell dissociation and invasive growth. We tested the hypothesis that the expression of Plex-B1, either alone or in association with Met, can be of predictive value for tumour progression.

Methods: The expression and distribution of Plex-B1 and Met were investigated by immunohistochemistry and immunofluorescence in 50 human neoplasias originating in the breast and ovary, and correlated with clinical–pathological data at diagnosis.

Results: Plex-B1 and Met were individually expressed in 14% and in 24% of the tumours, respectively. Plex-B1 and Met were co-expressed in 24/50 cases (48%), and in the majority of these (83%) Met was tyrosine phosphorylated. The expression of Plex-B1 or Met alone showed no significant correlation with tumour aggressiveness, whereas advanced stage tumours (III–IV) frequently showed Plex-B1–Met double-positive (9/13). Tumours co-expressing Plex-B1 and Met were characterised by worse grading and higher incidence of lymph node metastases. Out of 22 tumours with lymph node metastases, as many as 19 were Plex-B1 and Met double-positive (p=0.0008), and 17 expressed phosphorylated Met (p=0.002).

Conclusions: Plex-B1 assumes a predictive value for unfavourable outcome when co-expressed with Met.