Article type: Research Article
Authors: Valente, Guido; | Nicotra, Giuseppina | Arrondini, Marisa | Castino, Roberta | Capparuccia, Lorena | Prat, Maria | Kerim, Simonetta | Tamagnone, Luca | Isidoro, Ciro
Affiliations: Pathology Section, Department of Clinical and Experimental Medicine, Amedeo Avogadro University, Novara, Italy | Laboratory of Molecular Pathology, Department of Medical Sciences, Amedeo Avogadro University, Novara, Italy | Institute for Cancer Research and Treatment (IRCC), University of Torino Medical School, Candiolo (TO), Italy | Laboratory of Histology, Department of Medical Sciences, Amedeo Avogadro University, Novara, Italy | Cytogenetics Unit, Department of Laboratory Diagnostics, San Giovanni Hospital, Torino, Italy
Note: [] Corresponding authors: Dr. Guido Valente, MD, Dipartimento di Medicina Clinica e Sperimentale, Università del Piemonte Orientale “Amedeo Avogadro”, Via Solaroli 17, 28100 Novara, Italy. Tel.: +39 321 660666; Fax: +39 321 620421; E-mail: [email protected]. Dr. Ciro Isidoro, PhD, MD, Dipartimento di Scienze Mediche, Università del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy. Tel.: +39 321 660607; Fax: +39 321 620421; E-mail: [email protected] (author for editorial correspondence).
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). Conclusion: Plex-B1 assumes a predictive value for unfavourable outcome when co-expressed with Met.
Keywords: Plexin-B1, Met, CD100, tumour prognosis, lymph node metastases
DOI: 10.3233/CLO-2009-0504
Journal: Analytical Cellular Pathology, vol. 31, no. 6, pp. 423-436, 2009
