Prognostic value of E-cadherin, beta-catenin, CD44v6, and HER2/neu in metastatic cutaneous adenocarcinoma.
BACKGROUND
Our recent experience with a patient developing cutaneous metastases within 3 months of diagnosis of esophageal adenocarcinoma suggests that altered expression of the cellular adhesion molecules, E-cadherin and CD44v6, may have had a role to play in the rapid onset of metastases.


OBJECTIVE
To corroborate these findings, we designed a cross-sectional study to investigate the expression of select molecules involved in the metastatic cascade.


METHODS
E-cadherin, beta-catenin, CD44v6, and HER2/neu immunohistochemical stains were performed on archival materials of metastatic adenocarcinoma to the skin from 27 patients and the available corresponding primary tumors in 10 patients. The primary sites included breast (n = 10; 37%), gastrointestinal tract (n = 10; 37%), ovary (n = 1; 4%), thyroid (n = 2; 7%), lung (n = 1; 4%), and unknown primary (n = 3; 11%).


RESULTS
Expression of all markers was noted with the most significant increases observed in beta-catenin (26 of 27 cases; 96%), followed by CD44v6 (24 of 27 cases; 89%), E-cadherin (22 of 27 cases; 82%), and HER2/neu (11 of 27 cases; 41%). Contrasting expression of these molecules in the primary versus the metastatic tumors, enhanced expression of CD44v6 was observed in the cutaneous metastases relative to the primary in 6 of 10 (60%) cases. Of interest, 2 of these 6 cases (33%) also showed reduction in E-cadherin--a member of the cadherin family functioning as an invasion suppressor molecule.


CONCLUSIONS
These findings reinforce the complexities of the metastatic cascade and imply that the variation in adhesive properties of tumor cells is, perhaps, a consequence of the difference in density of the molecules mediating this process.
Pozdnyakova
Olga
O
Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Hoang
Mai M P
MM
Dresser
Karen A
KA
Mahalingam
Meera
M
D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D003430:Cross-Sectional Studies; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000556:secondary; D051176:beta Catenin / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D051176:beta Catenin; C112697:CD44v6 antigen