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Mutation Pattern of the p53 Gene as a Diagnostic Marker for Multiple Hepatocellular Carcinoma¹

Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104 [T. O., H. T., A. S., M. S., S. H.], and Clinical Medicine, Surgery, Tsukuba University, 1-1-1 Tennodai, Tsukuba City, Ibaraki 305 [T. O.], Japan

Hepatocellular carcinoma, sometimes shows multiple tumor nodules, therefore poses a problem of differential diagnosis between cancers of multifocal and those of metastatic origin. Conventionally, pathological criteria have been used for this purpose, but these are largely subjective. In order to facilitate more objective differential diagnosis of multiple hepatocellular carcinoma, we used the pattern of mutation of the p53 gene as a marker for each tumor nodule. We studied 58 nodules from 26 cases of multiple hepatocellular carcinoma using polymerase chain reaction-single strand conformation polymorphism analysis, a simple method for detecting mutations. p53 gene mutations were detected in 65% (17 of 26) of cases. The internodule mutation patterns were heterogeneous in 11 cases and homogeneous in 6, enabling a multifocal origin to be diagnosed in the former and a metastatic origin in the latter at the genetic level. Moreover, the origin of recurrent tumors was determined from the mutation pattern. It is concluded that analysis of p53 mutations seems to be useful for differentiating the origin of multiple cancers, since the information it yields is essentially objective.

¹ This sudy was supported by a Grant-in-Aid for the Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare of Japan.

² Awardee of a Research Resident Fellowship.

³ Supported by a Foreign Research Fellowship from the Foundation for Promotion of Cancer Research, Tokyo, Japan. Present address: Institute of Pathology, Verona University, Strada Le Grazie, 37134 Verona, Italy.

⁴ To whom requests for reprints should be addressed.

Received 1/13/92. Accepted 4/20/92.

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