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.