Abnormalities in Cell Cycle Regulators and Their Application to Molecular Diagnosis

• Abnormalities in Cell Cycle Regulators and Their Application to Molecular Diagnosis

AUTHOR(S)

Wataru YASUI

First Department of Pathology, Hiroshima University School of Medicine

SUMMARY

In many leading hospitals and laboratory centers in Japan, tissues of gastrointestinal organs account for the majority of samples in routine daily histopathological diagnosis. Certainly, histopathological diagnosis is extremely useful for definitive diagnosis or guidance as to therapy. However, diagnosis depending only on histomorphology is limited in certain respects and is unsuitable for diagnosis of the presence of cancer.

Based on recent integrated research in molecular pathology over the past 15 years, the details of genetic and epigenetic abnormalities in the course of development and progression of gastrointestinal cancer have been clarified. Particularly in various cell cycle regulators, it has been known that cyclin and cyclin-dependent kinase ( CDK ) ( positive regulators ), and CDK inhibitor ( negative regulator ) are related to gastrointestinal cancer. In addition, various diagnostic markers such as telomerase activity, genetic instability, tumor suppressor gene, and oncogenes ( growth factor receptor type ) were reported to be effective for the diagnosis of gastrointestinal cancer.

In this year 2000, it was announced that nearly the entire base sequence of the human genome had been determined. Following this achievement, genetic analysis by means of DNA microarray may become mainstream in the diagnosis of gastrointestinal tissues in the future. Genetic analysis may make clear the characteristics of each type of cancer; that is, commonality and specificity in the development/progression of each cancer can be found. When this occurs, diagnosis that is directly useful for genetic therapy or molecule-targeted therapy can be conducted through pathological examination. The comparison of morphological changes with the abnormalities of genes/molecules is the main benefit to the genetic analysis/diagnosis of histopathological samples. The ultimate objective of the field of pathology is that morphological abnormalities of all diseases described in pathology literature can be traced to gene abnormalities or molecular abnormalities.

KEY WORDS

Cell Cycle Regulator, Molecular Pathological Diagnosis, Gastrointestinal Cancer