Abstract

IntroductionActivated 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.MethodsThe 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.ResultsImmunohistochemical 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.ConclusionsIn 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.

Highlights

  • Activated leukocyte cell adhesion molecule (ALCAM) (CD166) is an immunoglobulin molecule that has been implicated in cell migration

  • In the present panel of breast cancer specimens, decreased levels of ALCAM correlated with the nodal involvement, the grade, the TNM stage, the Nottingham Prognostic Index (NPI), and the clinical outcome

  • 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

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Summary

Introduction

Activated leukocyte cell adhesion molecule (ALCAM) (CD166) is an immunoglobulin molecule that has been implicated in cell migration. ALCAM = activated leukocyte cell adhesion molecule; BSA = bovine serum albumin; H & E = hematoxylin and eosin; MEMD = melanoma metastasis clone D; NPI = Nottingham Prognostic Index; PCR = polymerase chain reaction; RT = reverse transcriptase; TNM = tumor, node, metastasis R478. ALCAM has five extracellular immunoglobulin domains (two NH2-terminal, membrane-distal variable- [V]-type folds and three membrane-proximal constant- [C2]-type immunoglobulin folds), a transmembrane region, and a short cytoplasmic tail [13]. It is involved in both homotypic/homophilic adhesion and heterotypic/heterophilic (to CD6) adhesion [13,14]. ALCAM has been shown to be involved in capillary tube formation [15] and in vessel invasion into cartilage in vitro [16]

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