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Significance of int-2/hst-1 Coamplification as a Prognostic Factor in Patients with Esophageal Squamous Carcinoma¹

Departments of Surgery [Y. K., M. U., N. A., Y. S., O. A.] and Molecular Biology [N. S.], Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan

The correlation between the clinical outcome in patients with esophageal squamous cell carcinoma and coamplification of the proto-oncogenes int-2 and hst-1, which are partially homologous to angiogenesis-inducing fibroblast growth factor, was analyzed retrospectively. Coamplification of these genes was examined by slot-blot hybridization using DNAs extracted from formalin-fixed and paraffin-embedded blocks of tissues. These tissues were obtained from 107 patients with esophageal squamous cell carcinoma who had undergone radical surgery. Int-2/hst-1 coamplification greater than 3-fold was observed in the primary tumors of 30 of 107 cases (28%), and in the metastatic lymph nodes of 12 of 40 cases (30%). The cumulative survival rate of patients with int-2/hst-1 coamplification in the primary tumors was significantly lower than that of the patients without coamplification (P < 0.001), and there were no significant differences between the clinicopathological backgrounds of the 2 groups. Int-2/hst-1 coamplification was also significantly correlated with a high incidence of eventual metastasis in distant organs in these patients. These results suggest that int-2/hst-1 coamplification is a new biological indicator of prognosis and distant organ metastasis in patients with esophageal squamous cell carcinoma.

¹ This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science and Culture.

² To whom requests for reprints should be addressed.

Received 9/12/90. Accepted 12/20/90.

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