The mutations in K-ras codon12 were thought to be most frequent and possibly the earliest mutation among the genetic alteration sequences of both ductal pancreatic adenocarcinoma and IPMN. 'IPMN adenoma' with slight or mild atypia may only have the K-ras gene aberration. However, it is still controversial whether K-ras mutation supports these neoplastic features. Some have said that it was observed in up to 100% of pancreatic adenoarcinoma, but was not detected in the non-neoplastic tissue of the pancreas [3, 22-24]. Others have said that it was also suggested that K-ras gene mutation occurs frequently in the multifocal hyperplastic foci of the pancreatic duct, and that the mutation may not have direct relevance to the carcinogenesis of pancreatic cancer .
When K-ras analysis was performed at the cellular level using sophisticated microdissection and molecular methods, K-ras mutations were detected in hyperplastic ductal changes in the pancreas with chronic pancreatitis , in disease free pancreas  and also in the normal epithelium of the pancreatic specimens containing carcinomas . In addition to this, ductal lesions in patients with chronic pancreatitis exhibit K-ras mutations without the additional indications of neoplastic transformation, such as severe dysplasia or mutated p53 protein. Therefore, for diagnostic and therapeutic purposes, apart from being namable as neoplasia, the detection of K-ras mutations should be supplemented by the demonstration of additional genetic alterations or clinical signs of malignancy .
Among the most commonly observed types of hyperplasia, such as muci-nous cell hyperplasia, ductal papillary hyperplasia and adenomatoid hyperplasia, the incidences of K-ras codon12 mutations were reported to be 55%, 61% and 48%, respectively [25, 27]. These differently defined hyperplastic lesions should be placed into the same category, with regard to the genetic alteration. In addition to this, these studies also suggest that the K-ras mutations observed among these lesions are not sufficiently supportive to confirm their neoplastic nature.
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