[95] c-MET Overexpression Is Associated with Breast Cancer Distant Metastasis and Loco-Regional Recurrence

Joseph P Bergeron, Hope T Richard, Jorge A Almenara, Michael O Idowu. Virginia Commonwealth University, Richmond, VA

Background: Dysregulation of the c-Met receptor tyrosine kinase has been shown to confer resistance to DNA-damaging chemotherapeutic agents and is also associated with overall poor prognosis in a variety of tumors. Several clinical trials are currently investigating the use of novel c-Met inhibitors as a potential target for future therapeutic modalities. In particular, the agent ARQ 197 (Ds-5178) is currently being tested in a clinical trial for lung carcinoma. Currently, limited information is available on the association of c-Met overexpression with distant metastatic or recurrent disease in breast carcinomas. This study evaluated the relationship between c-Met expression and distant metastases along with a variety of other clinico-pathologic parameters including Ki-67 expression, local recurrence, triple negative hormone receptor status, and lymph node status.
Design: The clinical outcome and pathologic characteristics of breast carcinoma cases from 1992 to 2008 with adequate follow up information were reviewed. A minimum of 60 months of follow-up was required for inclusion of cases without recurrence or metastases. For each case, tissue microarrays (TMA) were created by obtaining 1 mm cores in triplicate from different areas of the tumor using an automated TMA system (Beecher ATA-27). The specimens were stained with a rabbit polyclonal antibody to c-MET (Abcam, Ma USA). Cases with moderate to intense membranous staining were considered positive. Statistical significance was determined using a Chi-squared test.
Results: Of 281 cases, 84 had distant metastases and 33 had loco-regional recurrence. The median follow-up period for all cases was 72 months, and ranged from 12 to 228 months. A greater proportion of cases with distant metastases and cases with local recurrence were associated with c-MET positivity (67 vs 17, p <0.05) and (26 vs 7, p <0.05), respectively. Additionally, c-MET positivity was associated with high Ki-67 (>30%), triple negative hormone receptor status, axillary lymph node positivity, and high histologic grade.

 c-MET posc-MET neg 
% dist mets (n=84)80% (67)20% (17)1.1 x 10 e-5
% local recur (n=33)79% (26)21% (7)1.93 x 10e-5
% grade III (n=109)72%(79)28% (30)1.98 x 10e-5
% high Ki67 (n=95)75% (71)25% (24)3.22 x 10e-5
% triple neg (n=74)66% (49)34% (25)7.26 x 10e-6
% LN pos85% (97)15% (17)3.16 x 10e-7

Conclusions: c-MET positive breast carcinomas are associated with increased incidence of metastases and loco-regional recurrence. Therefore, c-MET may be a useful marker for prognosis as well as a potential therapeutic target.
Category: Breast

Monday, March 19, 2012 1:30 PM

Platform Session: Section B, Monday Afternoon


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