Multicentric and multifocal versus unifocal breast cancer: differences in the expression of E-cadherin suggest differences in tumor biology

Background: The aim of this study was to evaluate the expression of
the cell adhesion-related glycoproteins MUC-1, beta-catenin and
E-cadherin in multicentric/multifocal breast cancer in comparison
to unifocal disease in order to identify potential differences in
the biology of these tumor types. Methods: A retrospective analysis
was performed on the expression of MUC1, beta-catenin and
E-cadherin by immunohistochemistry on tumor tissues of a series of
112 breast cancer patients (total collective) treated in Munich
between 2000 and 2002. By matched-pair analysis, 46 patients were
entered into two comparable groups of 23 patients after
categorizing them as having multicentric/multifocal or unifocal
breast cancer. Matching criteria were tumor size, histology grade
and lymph node status; based on these criteria, patients were
distributed equally between the two groups (p = 1.000 each). Data
were analyzed with the Kruskal-Wallis and the Mann-Whitney tests.
Results: In the matched groups, we found a significantly
down-regulated expression of E-cadherin in multicentric/multifocal
breast cancer compared to unifocal disease (p = 0.024). The total
collective showed even higher significance with a value of p <
0.0001. In contrast, no significant differences were observed in
the expression of beta-catenin between multicentric/multifocal and
unifocal tumors (p = 0.636 and p = 0.914, respectively). When
comparing the expression of MUC1, E-cadherin and beta-catenin
within the unifocal group, we found a significant positive
correlation between E-cadherin and beta-catenin (p = 0.003). In the
multicentric/multifocal group we observed, in contrast to the
unifocal group, a significant decrease of MUC1 expression with
increased grading (p = 0.027). Conclusion: This study demonstrates
that multicentric/multifocal and unifocal breast cancers with
identical TNM-staging clearly differ in the expression level of
E-cadherin. We suggest that the down-regulation of E-cadherin in
multicentric/multifocal breast cancer is causally connected with
the worse prognosis of this tumor type.