CD44, A NEW PROGNOSTIC MARKER FOR NEUROBL ASTOMA

CD44 gene products are potential markers of aggressiveness in differen t tumor models, a result which prompted us to study clinical neuroblas toma (NB) specimens. CD44 expression was determined by immunostaining of 52 NE with a monoclonal antibody (J173) directed against an epitope common to all CD44 isoforms. All tumors were from patients (pts) with newly diagnosed NE treated with standardized protocols. They were cla ssified according to international criteria [II]. CD44 immunoreactivit y was detected in 37 tumors (71%). CD44 was expressed in 100% of favor able NE stages (1, 2 or 4S), but only 50% of advanced NE (stages 3 and 4) (p = 0.0001), suggesting that the absence rather that the overexpr ession of CD44 is a signal of tumor agressiveness. The cumulative even t-free survival was significantly longer in pts with CD44-positive tum ors as compared to pts with CD44-negative tumors (p < 10(-5)). More im portantly, progression-free survival was also significantly higher in CD44-positive pts within the high-risk group (p < 0.01). In univariate analyses, we tested the prognostic value of tumor expression of CD44 in comparison with tumor stage, age, tumor histology and presence or a bsence of N-myc proto-oncogene amplification. All five measures had si gnificant prognostic value. The expression of CD44 and the absence of N-myc amplification were the most powerful predictors of a favorable c linical outcome. In a multivariate analysis of these measures, CD44 ex pression and tumor stage were the only independent prognostic factors for the prediction of patient survival. NE is the first clinical model described in which tumor aggressiveness correlates with a repression rather than a stimulation of CD44 expression. We recommend the use of CD44 as an additional biological marker in the initial staging of neur oblastoma.