Expression of the cell to cell adhesion molecule, ALCAM, in breast cancer patients and the potential link with skeletal metastasis.

The activated leukocyte cell adhesion molecule (ALCAM) is involved in cell migration and adhesion. Decreased levels of ALCAM expression in breast cancer tissue are known to correlate with poor prognosis. The current study specifically investigated the ALCAM expression in tumours which developed skeletal metastasis. Fresh frozen primary breast cancer tissues (n=234) and non-neoplastic mammary tissue (n=34) were used. The distribution and location of ALCAM was assessed using immunohistochemical methods and the level of ALCAM was determined using quantitative RT-PCR. The results were analysed against the clinical and pathological data. ALCAM staining was largely membranous and cytoplasmic in normal epithelial cells and is significantly stronger than in cancer cells (p=0.023) and patients who develop skeletal metastasis (p=0.048). The ALCAM transcript levels were lowest in patients with skeletal metastasis (p=0.0048) but were also significantly lower in patients who developed local recurrence (p=0.040) and in those who died from breast cancer (p=0.0075). Patients with moderate and poor prognostic indices have a lower level than those with a good index (p=0.05 and p=0.0089 respectively) and ER-positive tumours show a lower level than ER-negative (p=0.043). Ductal carcinomas, 86% of the cohort, have a similar pattern of changes with skeletal metastasis patients having significantly lower levels (p=0.015). This study has, for the first time, shown that patients who develop skeletal metastasis tend to have the lowest levels of ALCAM transcripts in their breast cancers, a finding potentially useful for clinical practice.