DIAGNOSIS OF LARGE CELL LYMPHOMA BY SURVIVIN EXPRESSION

Yale University, New Haven CT

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Abstract

DESCRIPTION: (adapted verbatim from the investigator's abstract) The incidence of non-Hodgkin's lymphoma is increasing by 3-4% per year, second only to the rise of malignant melanoma and lung cancer. Despite the introduction of intensive combination therapy, half of these patients develop recurrences, chemoresistance, and die of the disease. The lack of simple diagnostic parameters to quickly identify such patients hampers a more successful approach to the disease. Deregulated expression of inhibitors of programmed cell death (apoptosis) is though to participate in lymphomagenesis by aberrantly increasing cell viability, favoring multi-drug resistance and the insurgence of transforming mutations. Recently, a novel IAP apoptosis inhibitor, survivin, was identified by Dr. Altieri, which is selectively expressed in common human cancers but not in normal adult tissues, in vivo. When analyzed for its diagnostic potential, the presence of survivin identified patients with prognostically unfavorable neuroblastoma, with reduced tumor cell apoptosis and p53 abnormalities in gastric cancer, and with shorter survival rates in colorectal cancer. In a pilot series of high-grade, large cell non-Hodgkin's lymphoma, survivin expression was associated with highly proliferative disease and frequent relapses. Therefore, the possibility that survivin expression may identify patients at risk of recurrent lymphoma can be postulated, and will constitute the focus of the present application. It is proposed to investigate the expression of survivin and of anti-apoptotic bcl-2, along with p53 abnormalities and mitotic and apoptotic indices, in 400 cases of large cell lymphoma of the LNH87 clinical trail sponsored by the GELA study group(Groupe d'Etudes des Lymphomes de l'adulte). The risk associated with survivin expression well be correlated with clinical parameters of disease progression and overall disease-free survival. The identification of a potential novel molecular tool for the predictive diagnosis of large cell lymphoma may provide a more rational and comprehensive approach to the treatment of the disease.