Co-expression of plexin-B1 and Met in human breast and ovary tumours enhances the risk of progression.
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.
Valente
Guido
G
Pathology Section, Department of Clinical and Experimental Medicine, Amedeo Avogadro University, Novara, Italy. guido.valente@med.unipmn.it
Nicotra
Giuseppina
G
Arrondini
Marisa
M
Castino
Roberta
R
Capparuccia
Lorena
L
Prat
Maria
M
Kerim
Simonetta
S
Tamagnone
Luca
L
Isidoro
Ciro
C
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D012307:Risk Factors
D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met