KIF14 mRNA expression is a predictor of grade and outcome in breast cancer
Purpose: Gain of chromosome 1q is a hallmark of breast cancer, and likely reflects oncogene amplification. We previously identified mitotic kinesin KIF14 as an overexpressed candidate oncogene in the 1q31.3-1q32.1 region of gain in breast cancer cell lines. KIF14 also showed overexpression in other cancers, notably an association with survival in lung tumors. Here, we evaluated KIF14 expression in primary breast tumors and associations with clinical variables.
Methods: KIF14 and MKI67 (encoding the Ki-67 proliferation marker) mRNA levels were measured by real-time RT-PCR in 99 breast tumors and 10 normal breast controls, and compared with clinical variables using standard statistical tests.
Results: KIF14 was overexpressed 10-fold on average in tumors relative to normals (t-test p = 0.000054); expression increased with grade (ANOVA p = 0.000006). Infiltrating ductal carcinomas had higher KIF14 levels than lobular (p = 0.017), and estrogen receptor (ER) negative tumors had higher KIF14 levels than ER positive tumors (t-test p = 0.030). KIF14 expression correlated positively with MKI67 mRNA level (Spearman r = 0.692, p = 0.000001), fraction of positive nodes (r = 0.227, p = 0.024), and percent invasive cells (r = 0.360, p = 0.0002), and negatively with percent fatty stroma (r = -0.258, p = 0.010), and percent normal epithelium (r = -0.291, p = 0.003). KIF14 overexpression predicted overall survival (univariate Cox p = 0.010), with an odds ratio of 3.60 (1.37-9.48), and disease-free survival (Kaplan-Meier p = 0.049) in 50 tumors with available outcome data.
Conclusions: KIF14 expression is tumor-specific and increased in highly proliferative, aggressive breast tumors. These findings are the first evidence of association between expression of a mitotic kinesin and prognostic variables in breast cancer.