Abstract 696: Loss of ALCAM function as a biologic basis for ethnic disparity in breast cancer

Abstract

Abstract Breast cancer affects African American women at a lower frequency than Caucasian women, yet progression of the tumor and mortality from the disease is higher among African Americans. The genetic and molecular contributions to this ethnic disparity are poorly understood. Activated leukocyte cell adhesion molecule (ALCAM) is a junctional adhesive molecule tethered at sites of cell-cell contact in epithelia, mesenchymal, neuronal, and connective tissues. Loss of ALCAM function, due to reduced transcript levels, and low membrane localization, is associated with increased mortality, and poor response to adjuvant therapy in breast cancer. In the current study, we tested the hypothesis that this phenomenon contributes to the ethnic disparity in breast cancer in the US. We studied cases of breast cancer in Atlanta among African American (n=90) and Caucasian (n=104) women. Immunohistochemical staining was used to study ALCAM expression in tumor and non-tumor adjacent breast tissues. Clinicopathological variables including histologic tumor grade, tumor size, lymph node involvement, estrogen receptor (ER), progesterone receptor (PR), and HER2-neu status were abstracted, and their relationship to ALCAM expression was analyzed. Membranous ALCAM (mALCAM) expression correlated significantly with tumor grade, with poorly differentiated tumors showing low ALCAM staining. In addition, mALCAM correlated positively with ER status (African American: p=0.0013; Caucasian: p=0.0008) and PR status (African American: p=0.025; Caucasian: p=0.0027) in both ethnic groups; however, there were no associations between ALCAM expression and tumor size, lymph node involvement, or HER2-neu status. Tumor expression of mALCAM in Caucasians was significantly higher than in African Americans (p<0.0001), while there was no difference in expression of cytoplasmic ALCAM between the two groups. To our knowledge, this is the first study to examine ALCAM expression in African American breast cancer, and to compare this phenotype with Caucasians. Our results indicate that markedly lower ALCAM expression may contribute to the poor prognosis of breast cancer among African Americans. Future studies will examine the genetic basis of this variation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 696. doi:1538-7445.AM2012-696