Does "clonal progression" relate to the development of intraductal papillary mucinous tumors of the pancreas?

Intraductal papillary mucinous tumors of the pancreas show a unique histologic feature in that the wide spectrum of intraductal epithelium is observed in the same pancreas. The aim of this study was to clarify whether or not the "clonal progression" relates to the development of this tumor. A total of 210 intraductal epithelium samples were microdissected from 23 resected specimens of intraductal papillary mucinous tumors of the pancreas, including nine carcinomas, five borderline tumors, and nine adenomas. After histologic grading (grades 1 to 4) of the individual epithelium, the K-ras point mutation and loss of heterozygosity in 9p21(p16) and 17p13(p53) were investigated. From the distribution of the K-ras point mutation of 210 microdissected specimens, an identical sequence of K-ras was demonstrated in the precursor lesions in most cases. K-ras mutation showed a single pattern, and the multiple or heterogeneous mutation pattern was not seen in this study. In the same ways, the distribution of loss of heterozygosity in 9p21(p16) and 17p13(p53) of 210 microdissected specimens was shown to be mostly clonal, without the presence of the genetic alterations. Such distributions of the identical genetic statuses in the precursor lesions are consistent with the presence of clonal progression during the development of this tumor.