Molecular-pathological diagnosis of gastrointestinal tissues and its contribution to cancer histopathology.

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 suppressor genes, cell cycle regulators, cell adhesion molecules and DNA repair genes. By analyzing these alterations in pathology specimens, we can improve differential diagnosis of cancer, obtain information of grade of malignancy, and identify patients at high risk for developing multiple primary cancers. 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 additional information of differential diagnosis, biological malignancy and tumor multiplicity could be obtained. Molecular-pathological diagnosis may provide a new approach to cancer diagnosis and novel therapeutics for the 21st century. Furthermore, the analysis of the genetic and epigenetic abnormalities in clinical materials may clarify the molecular mechanism of carcinogenesis and comparative morphological changes. From the analyses of p27KIP1 and telomerase in gastrointestinal adenomas, we have learned that morphological abnormality of the nucleus is an indicator for cells with immortality and malignant potential that must participate in super-early diagnosis (detection of true precancerous lesions) of gastrointestinal cancer. Molecular-pathological diagnosis thus contributes to detailed understanding of cancer histopathology and improves the histopathological diagnosis.