High Expression of<i>KIF14</i>in Retinoblastoma: Association with Older Age at Diagnosis

Abstract

PURPOSE: KIF14 a mitotic kinesin gene plays an important role in cytokinesis. Deregulation of KIF14 may be a pathway of tumor progression and results in decreased patient survival as seen in breast tumors. Recently, KIF14, a possible gene that drives gain of chromosome arm 1q (the most commonly gained chromosomal region in retinoblastoma), has been shown to be a strong oncogene candidate overexpressed by more than two orders of magnitude in retinoblastoma. This study was conducted to quantify the expression of KIF14 in human retinoblastoma tumors and correlate it with disease phenotype. METHODS: KIF14 expression was examined by using real-time RT-PCR in 30 retinoblastoma tumors with age at diagnosis between 3 and 68 months. Two 18-month-old, three adult (55-62 years), and three fetal (one 18 weeks' and another pooled retina of 18 and 20 weeks' gestation) retinas were used as the control. KIF14 expression was normalized to the housekeeping control gene TBP and compared with that in an 18-month-old control retina. The protein expression was confirmed in tumor cells by immunohistochemistry and phenotypic correlation was performed. RESULTS: KIF14 was expressed between 3- and 207-fold greater than 18-month-old retina in 30 retinoblastoma tumors (P < 0.0001). Immunohistochemistry revealed KIF14 localization to both nucleus and cytoplasm of tumor cells. KIF14 mRNA overexpression correlated significantly with older age at diagnosis (P = 0.006). There was no association with differentiation, invasion, or duration of the disease with KIF14 overexpression. CONCLUSIONS: Overexpression of KIF14 was confirmed in primary human retinoblastoma and showed that patients with an older age at diagnosis express significantly higher levels of KIF14.