E-Cadherin and -Catenin Are Dysregulated in Merkel Cell Carcinomas
S Serra, D Ghazarian, R Chetty. UHN, University of Toronto, Toronto, Canada
Background: Adhesion molecules are involved in epithelial integrity and polarity function. -catenin acts as adhesion molecule and transcription factor in the Wnt pathway. It interacts with E-cadherin, a transmembrane adhesion molecule also involved in cell-to-cell contact.
Design: The aim of the study was to examine the expression of -catenin and E-cadherin in Merkel cell carcinomas (MCC). Twenty-six MCC were retrieved from the archives of the Department of Pathology, UHN, and stained with -catenin and two antibodies (Ab) (against extracellular and cytoplasmic domains) to E-cadherin. Location of reactivity (membranous, cytoplasmic, nuclear), percentage of positive cells (<5%, 5-30%, >30%-70% and >70%, scored from 0 to 3, respectively) and intensity (negative, weak, moderate and strong; from 0 to 3, respectively) were recorded for both molecules.
Results: Of the 26 biopsies, 15 were males, aged from 59 to 96 years (average 69). Twenty MCC were primary tumors of the skin, 2 of the lip, 3 metastases to lymph nodes and 1 to the tonsil. The E-cadherin Ab recognizing the extracellular domain showed cytoplasmic positivity in 57.6% (15/26) of the cases, cytoplasmic/membranous in 1 and negative in 10 (38.4%). The intensity was weak in 12/26 (46%) cases and strong in 1. Eight of 26 (30.7%) cases showed 5-30% of the cells to be immunoreactive and 7/26 (27%) >30-70%. The immunoreactivity of the Ab against the cytoplasmic domain of E-cadherin was nuclear in 11/25 (44%) cases, nuclear/cytoplasmic in 8/25 (32%) and cytoplasmic only in 5/25 (20%), 1/25 case was negative and no tissue was available in one case. The intensity of the staining was strong in 12/25 (48%) and weak in 3/25 (12%) cases. In 19/25 (76%) cases, more than 70% of the tumors cells were positive with this Ab. Sixteen of 26 (61.5%) cases showed cytoplasmic immunoreactivity for -catenin, 27% (7/26) both cytoplasmic and nuclear and 11.5% (3/26) both cytoplasmic and membranous.The intensity of the immunoreaction was strong in 7/26 (27%) and weak in 3/26 (11.5%) cases. The majority of tumors showed immunoreactivity in 30-70% of cells.
Conclusions: Both -catenin and E-cadherin are dysregulated in all cases of MCC, with a loss of the normal membranous pattern and redistribution to the cytoplasm and nucleus. In addition, the staining pattern for E-cadherin depends on the type of E-cadherin Ab used. The Ab that recognizes the extracellular domain of the E-cadherin molecule results in loss of staining in some cases or cytoplasmic immunoreactivity, while the Ab against the cytoplasmic domain results in cytoplasmic and/or nuclear positivity.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 57, Wednesday Morning