抄録
Multiple genetic and epigenetic alterations of cancer-related genes and molecules are involved in the course of the development and progression of gastrointestinal cancers. These include telomerase activation, genetic instability and abnormalities of oncogenes, tumor suppresor genes, cell cycle regulators, cell adhesion molecules and DNA repair genes. Alterations of tumor suppressor gene such as p53 and APC are good genetic markers for differential diagnosis. Gene amplification and overexpression of oncogenes and growth factors/receptors such as c-met, c-erbB2, TGF α, EGF receptor and cyclins are biological markers of malignancy. Microsatellite instability is an indicator for high susceptibility of cancers like herediatry non-polyposis colorectal cancer as well as high risk for developing multiple cancers. Many of the genetic changes can be analyzed on paraffin-embedded biopsy specimens taken for the purpose of histopathological diagnosis. Since 1993, a system of molecular-pathological diagnosis was established and has been performed as a routine service in collaboration with Hiroshima City Medical Association Clinical Laboratory. More than 10, 000 cases of gastrointestinal biopsy and surgery have been analyzed and the reports of molecular diagnoses have been sent routinely to the clinicians. Additional new information of differential diagnosis and biological malignancy to the pure histopathological diagnosis could be obtained in about 15% of the cases by our molecular diagnosis strategy. Our diagnostic approach may contribute to the new "personalized medicine" in the next century by characterizing the individuality of cancer according to its genetic and epigenetic alterations. DNA chip technology will greatly promote the new direction of cancer diagnosis and therapeutics.
