1444 POSTER Evaluation of Hand-foot Syndrome (HFS) as a Potential Biomarker of Sunitinib (SU) Efficacy in Patients (pts) With Metastatic Renal Cell Carcinoma (mRCC) and Gastrointestinal Stromal Tumour (GIST)

Background: Mina53, a novel target gene of c-Myc, is overexpressed in various malignancies. Overexpression of Mina53 has been associated with poor prognosis in esophageal cancer, renal cell carcinoma, and neuroblastoma. We previously demonstrated that Mina53 is overexpressed in lung cancer patients from the early clinical stages. In addition, the enforced expression of Mina53 in NIH/3T3 cells, a mouse fibroblast cell line, induces cell transformation, and Mina53 transfected NIH/3T3 clones produce tumours in nude mice. In this study, we examined the association between disease prognosis and Mina53 expression in lung cancer patients. Materials and Methods: Mina53 expression was determined by immunohistochemistry and western blotting using lung cancer cell lines and lung cancer tissues. The survival rate was calculated according to the Kaplan–Meier method and the logrank test was used for assessing differences. Biological effects of Mina53 were evaluated by cell proliferation assay, cell cycle analysis, apoptosis assay, and in vitro cell invasion assay using Mina53 transfected A549 and H226B cells. Results: Patients with negative staining for Mina53 had significantly shorter survival than patients with positive staining for Mina53, especially in stage I or with squamous cell carcinoma. We hypothesized that Mina53 exerts different effects according to cancer cell type, inhibiting tumour progression in lung cancer cells. Growth of A549 transfected with pCAGGS/mina53 (expression plasmid) was inhibited. After transfection of pCAGGS/mina53 into A549, pre-G0/G1 phase cells increased in a time-dependent manner. In addition, early apoptotic cells were more frequently observed among cells transfected with pCAGGS/mina53 than those with pCAGGS. Because cell growth inhibition associated with apoptosis was not observed in H226B, we examined the possibility of an effect of Mina53 on cancer cell invasion. The number of invading cells transfected with pCAGGS/mina53 significantly decreased compared with those with pCAGGS, whereas transfection with mina53 shRNA increased the number of invading cells. Conclusions: Mina53 could be a possible favorable prognostic marker, especially in squamous cell carcinoma. Considering the results of biological effects of Mina53, is may play a role on inhibition of cancer progression.