PURPOSE:This retrospective study was undertaken to evaluate immunohistochemically the expression of CD44 standard protein and CD44v5 and CD44v6 isoforms in colorectal adenomas and early invasive cancers developing within adenomas as possible markers characterizing colorectal polyps with a more aggressive biologic potential.METHODS:Archival tissues of 81 consecutive locally resected colorectal polyps, comprising 57 colorectal adenomas and 24 carcinomas‐in‐adenomas, were stained immunohistochemically with the use of commercially available mouse monoclonal antibodies: SFF‐2 for CD44 standard protein, VFF‐8 for CD44v5, and VFF‐7 for CD44v6.RESULTS:Sixtythree percent of the colorectal polyps were positive for CD44 standard protein, 59 percent were positive for CD44v5, and 27 percent were positive for CD44v6. Ninetythree percent of the low‐grade adenomas were CD44 standard protein‐positive, in contrast to 50 percent of the high‐grade adenomas and only 42 percent of the carcinomas‐in‐adenomas (Kendall's Tau =−0.42;P<0.0001). CD44v6 expression was more frequently found in early invasive cancers (54 percent) than in high‐grade adenomas (25 percent) and low‐grade adenomas (7 percent). This difference also was statistically significant (Kendall's Tau‐b =0.39;P=0.00003). Surprisingly, a downregulation of CD44 standard protein expression was observed in the adenoma tissue adjacent to carcinomas (62 percent) and areas with high‐grade atypia (71 percent), compared with low‐grade adenomas (93 percent; Kendall's Tau‐b =−0.28;P=0.004).CONCLUSIONS:Our data suggest that CD44 standard protein and CD44 isoform v6 expression differs considerably in benign and malignant colorectal polyps. Clinical studies with larger patient groups could clarify the prognostic potential of CD44 further