病理形態診断と分子生物学

Morphological Diagnosis and Molecular Biology

要旨　ヒト全遺伝子配列の解読が終わると，これまで以上に新たに病理形態像と深く関わる分子やがんの生物像に深く関わる分子機構も明らかにされると考えられる．このような背景を基に，病理診断は形態診断としての疾患の存在診断にとどまるだけでなく，手術術式の選択に関わる情報や，化学療法または放射線療法など治療法選択に関わる病理診断情報を要求されると思われる．現在でも既に免疫染色を主体として分子生物学的手法が日常の病理診断に関わってきている．本稿では，消化管病理形態診断と分子生物学的検査について現況と今後の展望そしてその問題点について述べる．

　Recent development of molecular biology makes it possible to read the whole human genome sequence. This new molecular biological technology and information concerning the human genome sequence will facilitate the discovery of the molecular mechanism involved in the morphology and pathology of diseases. Molecular biology will become important for pathological diagnosis not only for accurate morphological diagnosis but for providing additional clinicopathological information useful for selection of therapy. The recent increase of information concerning molecular biology has already been routinely applied for pathological diagnosis by using immunohistochemical staining with various antibodies. Antibodies recognizing molecular function have also been developed and applied for studies. Amplificaion of epidermal growth factor-receptor (EGF-R) which belongs to the family of oncogene ERB has been reported to be associated with poor prognosis of esophageal carcinoma. EGF-R is stimulated and phosphorylated by EGF. A monoclonal antibody to phosphorylated EGF-R reactes specifically to activated EGF-R in cancer cells. We can find gene mutation immunohistochemically by using a mutation specific antibody. Polymerase chain reaction (PCR) -based techniques combined with a microdissection system using a laser beam can facilitate the detection of cell specific gene alterations and expression from pathological samples. Development of DNA chips and DNA microarray techniques can make it easy to investigate a variety of genes in a short time. Recent advanced techniques of molecular biology may add various factors of clinical information to morphological diagnosis and will be applied in routine pathological diagnosis in the near future.