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Gain of 5p15 Detected by Comparative Genomic Hybridization as an Independent Marker of Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma¹

Departments of Pathology [T. U., H. T., T. F., S. K., A. O., K. S.] and Surgery II [T. U., A. T., S. Y., T. A., H. T., M. O.], Yamaguchi University School of Medicine, Ube 755-8505, Japan

Comparative genomic hybridization was applied to 51 primary esophageal squamous cell carcinomas (ESCCs) to clarify the relation between DNA sequence copy number aberrations (DSCNAs) and the clinicopathology of the disease. The average number of DSCNAs was 10.9 DSCNAs/tumor (6.1 gains and 4.9 losses), ranging from 1–30 DSCNAs/tumor. Gain of 3q26-qter and loss of 18q22-qter were detected in >60% of stage I tumors and considered to play an important role in the development of ESCC. Whereas gain of 8q24-qter was observed in 82.6% (19 of 23) of stage III and IV cancers, it was seen in 27.3% (3 of 11) of stage I tumors. It is suggested that gain of 8q24-qter plays an important role in tumor progression. Gains of 8q24-qter and 20q12-qter and loss of 11q22–23 were linked to nodal metastasis (P = 0.0006, 0.002, and 0.02, respectively). Gains of 5p15 and 14q21 were associated with distant organ metastasis after surgery (P = 0.006 and 0.02, respectively). These observations suggest that nodal and distant organ metastases involve different genes. Gains of 5p15, 8q24-qter, and 14q21 were significantly associated with unfavorable prognosis (P = 0.0002, 0.007, and 0.04, respectively). Multivariate analysis revealed the 5p15 gain to be an independent prognostic marker with a higher significance than that of nodal status (risk ratio = 5.95; P = 0.001). The present findings indicate that comparative genomic hybridization analysis may be used to predict the likelihood of a poor or favorable outcome in cases of ESCC.

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