Development of a predictive assay for radiosensitivity of esophageal cancer

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Esophageal carcinoma is a challenging target for radiation therapy. In this study, we investigated significant predictive factors for raido-responsiveness of the esophageal cancer.We evaluated the significance of apoptosis and immunohistochemical staining for p53,Ki-67,c-erbB-2(HER-2/neu),Ku(p70/p80) and DNA-PKcs for predictive markers of the responsiveness to chemoradiotherapy in esophageal squamous cell carcinoma. This retrospective analysis consist of 34 patients with esophageal squamous cell carcinoma in whom tumor biopsy was performed before treatment. Among these factors, only C-erbB-2/HER-2/neu oncoprotein expression was significant(P=0.02), though it did not correlate with survival.Then, to sensitize the radiation effect on the esophageal cells, we evaluated the effect of an anti-HER-2/neu antibody trastuzumab on the proliferation, cell cycle distribution, and radiosensitivity of esophageal cancer cell lines. Flow cytometry and IHC revealed that 2 esophageal cancer cell lines showed HER-2/neu expression, while other 4 esophageal cancer cell lines were negative. Although trastuzumab alone had no effect on the esophageal cancer cell lines, the combination of 10μg/ml trastuzumab with radiation showed a synergistic effect on the HER-2/neu expressing cell lines.We further analyzed transcriptional changes after ionizing radiation in different cell lines to identify other factors involving radiosensitivity. After completing clonogenic survival assays, we selected two cell lines with different radiosensitivities. Subsequently, they were investigated by using a technique of DNA microarray, and we then categorized the upregulated genes into 10 groups. Between the two cell lines, the difference in the percentage of DNA repair/replication category was the largest, and this category was present at a greater percentage with radioresistant cell line