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CD44 standard and variant isoform expression in human epidermal skin tumors is not correlated with tumor aggressiveness but down‐regulated during proliferation and tumor de‐differentiation
Author(s) -
Seelentag Walter K. F.,
Günthert Ursula,
Saremaslani Parvin,
Futo Eva,
Pealtz Madeleine,
Heitz Philipp U.,
Roth Jürgen
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960621)69:3<218::aid-ijc12>3.0.co;2-3
Subject(s) - cd44 , biology , immunostaining , immunohistochemistry , pathology , metastasis , cellular differentiation , cancer research , cancer , cell , immunology , medicine , gene , biochemistry , genetics
CD44 isoforms have been reported to be involved in tumor invasion and metastasis formation. Normal human skin expresses high levels of CD44 isoforms, but little is known about their expression in epidermal skin tumors. Expression of CD44 standard (CD44s) and variant exon (CD44v3, ‐v4, ‐v5, ‐v6, ‐v9)‐encoded gene products has been studied in 74 benign, semi‐malignant and malignant human epithelial skin tumors using a panel of well‐characterized, variant exon‐specific monoclonal antibodies (MAbs). Sensitivity and resolution of the immunohistochemical staining in paraffin sections was substantially improved by using microwave‐based antigen retrieval and an optimized streptavidin‐biotin‐peroxidase technique. Immunostaining was evaluated semi‐quantitatively and correlated with tumor type and degree of histological differentiation by non‐parametric statistical tests. Furthermore, the relationship between CD44 expression and cellular proliferation rate as defined by the Ki‐67 antigen was analyzed in basal cell carcinomas. We found a significant correlation between tumor type and CD44 isoform expression. Basal cell carcinomas exhibited the weakest staining and keratoacanthomas the strongest. Squamous cell carcinomas ranged in between, with a tendency to down‐regulate CD44 expression upon de‐differentiation. In basal cell carcinomas, an inverse relationship between CD44 expression and proliferation rate was directly demonstrated at the cellular level using double immunolabeling. Our data indicate that qualitative and quantitative changes in CD44 splice‐variant expression in human skin tumors do not correlate with invasive and metastatic potential but are rather related to the degree of tumor differentiation. © 1996 Wiley‐Liss, Inc.