Correspondence

CD44 -- A New Prognostic Marker for Neuroblastoma

N Engl J Med 1993; 329:1965December 23, 1993

Article

To the Editor:

CD44 is a cell-surface glycoprotein involved in cell-cell and cell-matrix interactions1. CD44 isoforms are expressed during progression and metastasis in colon and breast cancer and in non-Hodgkin's lymphoma2-4. We investigated the prognostic importance of the expression of CD44 in neuroblastoma, one of the most common cancers in children.

CD44 expression was determined by immunostaining 52 neuroblastomas with a monoclonal antibody (J173) directed against an epitope common to all CD44 isoforms1. All tumors were from children with newly diagnosed neuroblastoma treated with standard protocols. The tumors were classified according to international criteria (stages 1 and 2, localized neuroblastomas; stages 3 and 4, locally and regionally growing and distantly metastatic neuroblastomas; and stage 4S, neuroblastomas in children under one year of age, with metastases restricted to skin, liver, and bone marrow, usually regressing spontaneously)5.

CD44 immunoreactivity was detected in 37 of the 52 tumors (71 percent); CD44 was expressed in 100 percent (all 22) of the less advanced neuroblastomas (stages 1, 2, and 4S) but in only 50 percent (15 of 30) of the more advanced neuroblastomas (stages 3 and 4) (P<0.001). These results suggest that the absence rather than the overexpression of CD44 characterizes aggressive neuroblastomas. We compared the survival of patients whose tumors expressed CD44 with the survival of those whose tumors did not (Figure 1Figure 1Progression-free Survival in 52 Patients with CD44-Positive and CD44-Negative Neuroblastomas.). The cumulative progression-free survival was significantly better in patients with CD44-positive tumors than in those with CD44-negative tumors (P<0.001). More important, progression-free survival was also significantly better in patients with advanced neuroblastomas that were positive for CD44 (P<0.001).

In univariate analyses, we compared the prognostic value of CD44 expression with the prognostic value of the stage of the tumor, the patient's age, the histologic characteristics of the tumor, and the presence or absence of amplification of the N-myc proto-oncogene. All five measures had significant prognostic value. The expression of CD44 and the absence of N-myc amplification were the strongest predictors of a favorable clinical outcome. In a multivariate analysis of these measures, CD44 expression and tumor stage were the only independent predictors of survival.

In neuroblastomas, unlike other tumors, the absence of CD44 expression indicates aggressiveness. We recommend the use of CD44 as an additional biologic marker in the initial evaluation of patients with neuroblastoma.

M.C. Favrot, M.D., Ph.D.
V. Combaret, Ph.D.
C. Lasset, M.D.
Centre Leon Berard, 69008 Lyon, France

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