CD44 - A marker of squamous differentiation in adenosquamous neoplasms

Objective.-To test the hypothesis that CD44 standard (CD44[s]) and its othe r variants, CD44v6 and CD44v7-8, might be useful markers of squamous differ entiation in epithelial tumors. Design.-We studied expression of CD44(s), CD44v6, and CD44v7-8 using immuno histochemistry in human tumors that had squamous differentiation, glandular differentiation, or both arising in the colon, stomach, esophagus, lung, p ancreas, gallbladder, or uterus/cervix, as well as in adjacent nonneoplasti c tissues. Formalin-fixed, paraffin-embedded archival tissue specimens of 3 3 adenosquamous tumors were used. All were stained with monoclonal antibodi es against a conserved portion of CD44(s) and its variants, CD44v6 and CD44 v7-8, using the avidin-biotin peroxidase method. Results.-CD44(s) and its variants consistently and strongly stained areas o f tumors with well-developed squamous differentiation. These markers also c onsistently and strongly stained normal squamous mucosa. Reactivity for CD4 4 and its variants was lacking in normal glandular type epithelium and in a denocarcinomas composed entirely of well-differentiated mucin-producing gla nds. Areas of well-differentiated carcinoma, both squamous and adenocarcino ma, were consistent with respect to both extent and intensity of staining. Staining in lymph nodes was similar to that in the primary tumors, with wel l-differentiated squamous foci being consistently positive, well-differenti ated mucin-producing adenocarcinoma foci consistently negative, and poorly differentiated foci showing variable staining. Although staining was less i ntense with the variants, it followed the same staining pattern as found fo r CD44(s). No differences in the extent or intensity of staining were ident ified in the metastatic versus primary tumor foci, nor was any difference i dentified between superficial and deeply invasive areas of primary tumors. Conclusions.-Our study shows that CD44(s) and its variants are good markers of squamous epithelial differentiation in several types of normal epitheli um and tumors, and that these markers can identify areas of well- to modera tely differentiated elements in adenosquamous neoplasms. However, poorly di fferentiated tumors show an inconsistent staining pattern with CD44, such t hat it cannot be used as a reliable and practical marker of squamous differ entiation in poorly differentiated neoplasms.