Immunohistochemical Detection of Cyclin A in Wilms Tumor

Introduction Cyclins displays oscillatory expression during the cell cycle. They regulate the activity of CDKs, and, together with CDKs, they form holoenzymes that phosphorylate regulatory substrates like retinoblastoma proteins (pRb) and p107 (1,2). Thus far, 14 different mammalian cyclins are known, named cyclins A-J (3). Cyclins are usually grouped into G1 cyclins, such as Cyclin E, which controls the G1/S transition, and mitotic cyclins, such as Cyclin B, which is required for entry into mitosis (4). Cyclin A is the only cyclin known to play essential role not only in mitosis, but also in DNA replication (5). This, 60 kd protein, appears to be rate-limiting for initiation of DNA replication and is specifically localized to nuclear replication foci (6, 7). Wilms tumor, one of the most common solid malignancies in childhood, is highly responsive to chemotherapy and affected children usually have a good prognosis with a reported 5-year survival rate of more than 80% (8). Abnormalities of the cell cycle are important in the process of carcinogenesis. Immunohistochemical determination of the expression of various cyclins and CDKs in tumor cells has recently been applied to evaluate cancer growth (9,10,11). There are few reports on Cyclin A as a marker of proliferative cell fraction in cancer (12, 13, 14, 15, 16, 17, 18). The aim of this study was to investigate the expression of Cyclin A protein in normal kidneys as well as in Wilms tumor by immunohistochemistry and to correlate the results with tumor stage, histological type and prognostic group.