CD44 variant overexpression in gallbladder carcinoma associated with tumordedifferentiation

BACKGROUND, Recent studies have suggested a correlation between increased o r decreased expression of CD44 variant molecules and turner metastasis. CD4 4 expression in gallbladder carcinoma was examined and compared with tumor differentiation. METHODS. Eighty-three samples of gallbladder carcinoma, 17 gallbladder aden oma samples, and 66 normal control mucosa samples were stained immunohistoc hemically for CD44 standard form (CD44s), variant 3 (CD44v3), and variant 6 (CD44v6). RNA extracted from nine patients with carcinoma also was investi gated with reverse transcriptase-polymerase chain reaction (RT-PCR) analysi s and Southern blot hybridization (SB) for the CD44 gene. RESULTS. Normal gallbladder mucosa showed strong, membranous staining for C D44s but not for CD44v3 or CD44V6. In gallbladder tumors, CD44s was stained as strongly as it was in normal mucosa, but immunoreactivity for CD-44v3 a nd CD44V6 also was significant. In well differentiated, advanced adenocarci nomas (n = 38), CD44s immunoreactivity was significantly lower in the invas ive component than in the intramucosal component of the tumors (P = 0.0048) . Immunoreactivity for CD44v3 and CD44v6 in moderately and poorly different iated areas was significantly higher than in well differentiated areas (P < 0.0001 and P = 0.0378, respectively). RT-PCR and SBH signals for CD44v3 an d CD44V6, including exons 7 and 10, were strong in carcinoma samples bur we ak in normal samples, in line with the results of immunohistochemistry. The prognosis of patients with gallbladder carcinoma was not associated signif icantly with altered expression of CD44s, CD44v3, or CD44v6. CONCLUSIONS. The current study demonstrated that CD44 variant overexpressio n in patients with gallbladder carcinoma was linked closely with histologic dedifferentiation rather than clinicopathologic factors, including prognos is. (C) 2001 American Cancer Society.