Activated leukocyte cell adhesion molecule in breast cancer: prognostic indicator

Judy A King¹^,2^,3 , Solomon F Ofori-Acquah³^,4, Troy Stevens²^,3, Abu-Bakr Al-Mehdi²^,3, Oystein Fodstad⁵ and Wen G Jiang⁶

¹Department of Pathology, University of South Alabama, Mobile, Alabama, USA

²Department of Pharmacology, University of South Alabama, Mobile, Alabama, USA

³Center for Lung Biology, University of South Alabama, Mobile, Alabama, USA

⁴Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, Alabama, USA

⁵Cancer Research Institute, University of South Alabama, Mobile, Alabama, USA

⁶Department of Surgery, University of Wales College of Medicine, Cardiff, UK

author email corresponding author email

Breast Cancer Res 2004, 6:R478-R487doi:10.1186/bcr815


Published:	28 June 2004

Abstract

Introduction

Activated leukocyte cell adhesion molecule (ALCAM) (CD166) is an immunoglobulin molecule that has been implicated in cell migration. The present study examined the expression of ALCAM in human breast cancer and assessed its prognostic value.

Methods

The immunohistochemical distribution and location of ALCAM was assessed in normal breast tissue and carcinoma. The levels of ALCAM transcripts in frozen tissue (normal breast, n = 32; breast cancer, n = 120) were determined using real-time quantitative PCR. The results were then analyzed in relation to clinical data including the tumor type, the grade, the nodal involvement, distant metastases, the tumor, node, metastasis (TNM) stage, the Nottingham Prognostic Index (NPI), and survival over a 6-year follow-up period.

Results

Immunohistochemical staining on tissue sections in ducts/acini in normal breast and in breast carcinoma was ALCAM-positive. Differences in the number of ALCAM transcripts were found in different types of breast cancer. The level of ALCAM transcripts was lower (P = 0.05) in tumors from patients who had metastases to regional lymph nodes compared with those patients without, in higher grade tumors compared with Grade 1 tumors (P < 0.01), and in TNM Stage 3 tumors compared with TNM Stage 1 tumors (P < 0.01). Tumors from patients with poor prognosis (with NPI > 5.4) had significantly lower levels (P = 0.014) of ALCAM transcripts compared with patients with good prognosis (with NPI < 3.4), and tumors from patients with local recurrence had significantly lower levels than those patients without local recurrence or metastases (P = 0.04). Notably, tumors from patients who died of breast cancer had significantly lower levels of ALCAM transcripts (P = 0.0041) than those with primary tumors but no metastatic disease or local recurrence. Patients with low levels of ALCAM transcripts had significantly (P = 0.009) more incidents (metastasis, recurrence, death) compared with patients with primary breast tumors with high levels of ALCAM transcripts.

Conclusions

In the present panel of breast cancer specimens, decreased levels of ALCAM correlated with the nodal involvement, the grade, the TNM stage, the NPI, and the clinical outcome (local recurrence and death). The data suggest that decreased ALCAM expression is of clinical significance in breast cancer, and that reduced expression indicates a more aggressive phenotype and poor prognosis.