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.