Insulin-Like Growth Factor Receptor in Breast Cancer
Lauren A McLendon, Cynthia Cohen, Samip Patel, Roberto Diaz, Stephen Schmechel, Amy Adams, Gabriela M Oprea-Ilies. Emory University, Atlanta, GA; University of Minnesota, Minneapolis, MN
Background: Insulin-like Growth Factor Receptor (IGFR) plays a fundamental role in cell growth and malignant transformation and is an important inhibitor of apoptosis. While cells lacking IGFR have prolonged cell cycle kinetics, cells overexpressing this tumor marker demonstrate a decreased susceptibility to apoptosis in vitro. IGFR is a membrane-bound heterotetramer with intrinsic tyrosine kinase activity and multiple downstream targets including Ras and Raf. Prior studies have shown that IGFR plays a role in proliferation of breast tissue and is over-expressed in some breast cancers (BC).
We studied the expression of IGFR in BC by immunohistochemical (IHC) methods in a large series of hormone receptor positive and triple negative tumors (TNT). IGFR may be of interest in BC as a target for additional adjuvant treatment.
Design: Invasive mammary carcinomas (IMC) diagnosed during a 7-year period were reviewed. The IMC markers ER, PR, and Her-2 scored by the new CAP standards were included. The tumors were studied as Her-2 positive, TNT, and hormone receptor positive, which includes ER and PR positive cancers. Tissue microarrays (TMAs) were constructed with two 1 mm representative cores from each IMC and were stained with IGFR monoclonal antibody. The scoring of the IHC results was semiquantitative, using 0-3 for intensity and a percentage of tumor cells staining. Tumors that scored 2-3 for intensity with ≥10% of tumor cells staining were considered positive.
Results: Of the 350 IMC tumors stained for IGFR, 327 are positive (93.4%). The age at diagnosis varies from 24-90 years, and the relationship between IGFR positivity and age is not significant. IGFR positivity is lower in TNT than non-TNT (92.2% vs 94.2 %; p = 0.01). IGFR positivity was more prevalent in hormone receptor positive IMC than in hormone receptor negative tumors (97.4% vs 88.5%; p <0.001). Positivity of IGFR in Her-2 positive/hormone receptor negative IMC is significantly lower than in combined TNT and hormone receptor positive tumors (60.0% vs 93.9%; p = 0.01). Of African American patients, 198 of 218 (90.8 %) were positive for IGFR, while Caucasian patients had IGFR positive tumors in 107 of 109 (98.2%) with p <0.001.
Conclusions: 1. There is differential expression of IGFR among breast cancers, and this expression is related to the tumor markers: ER, PR, and Her-2.
2. IGFR positivity is related to patient race.
3. There is no correlation between the age of diagnosis of IMC and IGFR positivity.
4. IGFR positive breast tumors could be amenable to specific anti-tyrosine kinase type drugs.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 31, Wednesday Morning