Spontaneous hepatocarcinogenesis in recombinant inbred mouse strains: Correlation with serum levels of alpha-fetoprotein

The histology of spontaneous liver tumors and serum AFP levels were determined in seven Recombinant Inbred mouse Strains (RIs) whose progenitors differ markedly in spontaneous liver tumor incidence. The seven RIs were derived from a segregating F2 generation of C₅₇BL/6N (C₅₇) female x C₃H/HEN (C₃H) male mice. Liver tumors consisted of adenomas, adenomas with atypical changes and hepatocellular carcinomas (hepatomas). Thirty-five percent of mice with adenomas and 71% of mice with hepatomas had elevated serum AFP levels. Mice with hepatomas had higher average serum AFP levels than mice with adenomas, and the average size of hepatomas was larger than the average size of adenomas. However, there was no correlation between either tumor size or histology and serum AFP level, when comparing individual tumors within an RI strain. The elevated levels of serum AFP did not distinguish between mice with benign adenomas, adenomas with atypical changes or hepatomas. There were 33 mice that presented with adenomas or hepatomas that exhibited normal serum AFP levels, and 6 mice with elevated serum AFP levels had no demonstratable adenomas or hepatomas. The measurement of serum AFP levels continues to provide a rapid and relatively inexpensive method of screening mice for spontaneous hepatocarcinogenesis. However, we conclude from these studies that even in genetically identical animals in a given RI strain, for precise assessment of tumor incidence, other methods should be used in addition to serum AFP measurement, such as laparotomy or histologic examination.