Prognostic Value of E Cadherin beta Catenin CD44v6 and HER2 neu in Metastatic Cutaneous Adenoca by ProQuest


More Info
									Prognostic Value of E-Cadherin, -Catenin, CD44v6, and
  HER2/neu in Metastatic Cutaneous Adenocarcinoma
      Olga Pozdnyakova, MD, PhD; Mai M. P. Hoang, MD; Karen A. Dresser, BS; Meera Mahalingam, MD, PhD, FRCPath

● Context.—Our recent experience with a patient devel-                      Results.—Expression of all markers was noted with the
oping cutaneous metastases within 3 months of diagnosis                  most significant increases observed in -catenin (26 of 27
of esophageal adenocarcinoma suggests that altered ex-                   cases; 96%), followed by CD44v6 (24 of 27 cases; 89%),
pression of the cellular adhesion molecules, E-cadherin and              E-cadherin (22 of 27 cases; 82%), and HER2/neu (11 of 27
CD44v6, may have had a role to play in the rapid onset of                cases; 41%). Contrasting expression of these molecules in
metastases.                                                              the primary versus the metastatic tumors, enhanced ex-
  Objective.—To corroborate these findings, we designed                   pression of CD44v6 was observed in the cutaneous metas-
a cross-sectional study to investigate the expression of se-             tases relative to the primary in 6 of 10 (60%) cases. Of
lect molecules involved in the metastatic cascade.                       interest, 2 of these 6 cases (33%) also showed reduction
  Design.—E-cadherin, -catenin, CD44v6, and HER2/neu                     in E-cadherin—a member of the cadherin family function-
immunohistochemical stains were performed on archival                    ing as an invasion suppressor molecule.
materials of metastatic adenocarcinoma to the skin from                     Conclusions.—These findings reinforce the complexities
27 patients and the available corresponding primary tu-                  of the metastatic cascade and imply that the variation in
mors in 10 patients. The primary sites included breast (n                adhesive properties of tumor cells is, perhaps, a conse-
   10; 37%), gastrointestinal tract (n 10; 37%), ovary (n                quence of the difference in density of the molecules me-
   1; 4%), thyroid (n       2; 7%), lung (n    1; 4%), and               diating this process.
unknown primary (n        3; 11%).                                          (Arch Pathol Lab Med. 2009;133:1285–1290)

T   he growing incidence of adenocarcinoma has spurred
     interest in the identification of molecules or markers
that delineate patients at a higher risk of metastases. The
                                                                         cance of these molecules. For example, although the link
                                                                         between overexpression of HER2/neu and poor prognosis
                                                                         in breast cancer and, albeit in select studies, esophageal
weakening of the cell-cell adhesion mechanisms is a basic                adenocarcinoma, is a well-established one, others have
prerequisite for tumor metastasis to occur. This weakening               shown that its utility in the latter is limited to defining a
involves changes in homotypic cell-cell adhesion, hetero-                particular histologic subtype of esophageal adenocarci-
typic cell-cell adhesion, and interactions of cells with the             nomas.4 Also, although reduction or loss of expression of
extracellular matrix at the primary tumor site.1 Each of the             E-cadherin has been documented in neoplasms originat-
molecules selected in the current study contribute to some               ing in the gastrointestinal tract, redistribution has been
of the above steps, all of which appear crucial in the met-              noted in others, including those originating in the thyroid
astatic cascade. Briefly, HER2/neu is functionally integrat-              and the breast.5 These contradictory results encouraged us
ed with the epithelial-mesenchymal transformation that                   to perform a study to determine the expression of select
the tumor cells have to undergo to acquire migratory ca-                 proto-oncogenes and cellular adhesion molecules, with a
pabilities; the lymphocyte homing receptor CD44v6, an                    view to defining a marker that helped identify a biologi-
ubiquitous cell surface adhesion molecule, is involved in                cally aggressive neoplasm. A comparative study with the
cell-cell and cell-matrix organization; the physical associ-             primary tumor, in those cases in which it was available,
ation of E-cadherin and -catenin is believed to be critical              was also performed in an effort to better understand the
to homotypic cell-cell adhesion.2,3                                      development of a metastatic phenotype.
   Conflicting data exist regarding the prognostic signifi-
                                                                                        MATERIALS AND METHODS
                                                                           The study was approved by the UMass Medica
To top