CXCL12/CXCR4 Transcripts Levels of Expression Are Linked to Distant Metastasis and DFS Outcome in Breast Carcinoma
A Rouquette, M Cornic, E Blot, JM Picquenot, S Laberge-Le Couteulx. CRLCC Henri Becquerel, Rouen, France
Background: Breast carcinoma is the main cause of cancer-related deaths in occidental women and is mainly due to distant metastatic disease. Recent works suggest an involvement of chemokine CXCL12 and CXCR4 in the metastatic process, in both stroma and tumor cells. We assessed the prognostic value of CXCR4 and CXCL12 transcripts in breast carcinoma and correlated these value with immunohistochemical staining and "classical" prognostic factors.
Design: In a series of 113 patients who had surgery between january 2001 and december 2003 with primary breast cancer, with a minimum follow-up 24 months and for which frozen materiel and paraffin embedded tumor was available we did the following analysis: Tissue micro-array Immunohistochemistry for antibodies: Estrogen Receptor, Progesterone receptor, HER2, Cytokeratins 5-6 and 14, CXCR4 (clone Ab2074 and clone MAB172). Real-time RT-PCR for CXCR4 short (CXCR4s) and long(CXCR4l) transcripts, CXCL12 transcripts alpha(CXCL12a), beta(CXCL12b) and gamma(CXCL12g).
Results: Among the patients included, with an average follow-up of 52 months, 12 developped distant metastasis. Patients with lymph nodes metastasis, high grade tumors and absence of hormonal receptors(HR) expression were more likely to develop distant metastasis. Immunohistochemical analysis with CXCR4 with either antibody was not correlated with distant metastasis or lymph node metastasis. There was poor correlation between different CXCR4 antibodies result (kappa 0.29) and no correlation between quantitative RT-PCR results and CXCR4 immunohistochemichal results. CXCR4s level was more elevated in patients who developped distant metastasis(p=0.05) and seemed to have an adverse effect on DFS (p=0.07). CXCR4l showed lower level of expression than CXCR4s and also had an impact on DFS(p=0.06). There was a slight correlation between grade and level of level of expression of both transcripts and grade (p=0.08). CXCL12a and CXCL12b levels were inversely linked to grade (p=0.03) and HR expression (p=0.03). There was no relationship between CXCR12 transcripts and distant metastasis or lymph node metastasis.
Conclusions: Our work confirms a potential involvement of the CXCR4/CXC12 signalling in metastatic process. For the first time, the impact of alternative transcript is assessed and suggests new physiopathological mechanisms. It also shows that CXCR4 immunohistochemical staining is not the best way to evaluate the role of these molecules.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 11, Wednesday Afternoon