炎症性腸疾患における癌化・発育進展―潰瘍性大腸炎における大腸癌の組織発生

Histogenesis of Colorectal Carcinoma in Ulcerative Colitis

要旨　長期経過全大腸炎型潰瘍性大腸炎（UC）に合併したSM以深浸潤癌10症例11病変の随伴粘膜内部12病変を対象に，その病理形態像（肉眼と組織），p53蛋白過剰発現，細胞増殖動態，細胞粘液形質，を検討した．肉眼的には，周囲とは境界不明瞭な丈の低い顆粒状・結節状・不整扁平隆起，または平坦病変の広範囲進展（10/11が30mm以上の大きさ）を示した．組織学的には腺腫はなく，全例UC-IVであったが，低分化化傾向，高分化低異型度癌（表層分化，細胞分化異常などを伴う）などを特徴とし，3病変はUC-IIIを伴っていた．p53蛋白過剰発現率はUC-IVで75.0％，UC-IIIで66.7％と高率であり，2病変では随伴粘膜内腫瘍周囲の“組織学的に腫瘍と判定できない粘膜"にも同蛋白過剰発現がみられた．細胞増殖動態は，diffuse typeかbasal typeが主体を占め，superficial typeはなかった．71.4％で胃型粘液形質MUC5ACの異常発現があり，その全例で背景炎症粘膜にもMUC5ACが発現していた．以上のことから，UCの炎症粘膜における大腸癌の組織発生には以下の経路が推定された．① 長期の慢性持続性炎症による胃化生粘膜→ ② 腫瘍としての形態形質を獲得する以前に生じるp53遺伝子異常→ ③ 異型の弱い腫瘍（表層分化や細胞分化異常を伴う）の発生とその広範囲粘膜内進展→ ④ 高分化高異型度癌へのprogression→ ⑤ SM以深浸潤，または ⑤ 粘膜内高分化型腫瘍の脱分化→ ⑥ SM以深浸潤．

　Twelve lesions of intramucosal neoplasias accompanied by 11 SM-carcinomas complicating long-standing entire colitis type ulcerative colitis（UC）were studied. Macroscopically they showed wide spread low granular, nodular, irregular plaque-like elevations or flat lesions without distinct margins to the surrounding inflammatory mucosa. Histologically, all of them were UC-IV which is characterized by a tendency towards dedifferentiation tendency, low-grade carcinoma（associated with superficial differentiation and/or aberrant cellular differentiation）, and 3 of them accompanied UC-III. High rate of p53 protein over expression was seen in 75.0％ of UC-IV, and 66.7％ of UC-III lesions, respectively. Furthermore in 2 lesions, protein over expression was identified within adjacent non-neoplastic-looking inflammatory mucosa. Proliferative compartments were located either diffusely or basally. Aberrant expression of MUC5AC gastric type mucin was demonstrated in 71.4％ of the cases, and it was seen in the background inflammatory mucosa, as well. From the above findings, the histogenetic pathway of colorectal carcinoma was speculated as follows : ① Gastric metaplasia of colorectal mucosa affected by long-standing inflammation→ ② p53 gene mutation in histologically non-neoplastic looking mucosa→ ③ development of low grade neoplasia（with superficial differentiation and/or aberrant cellular differentiation）→ ④ progression to the well-differentiated high grade carcinoma→ ⑤ invasion of the submucosa, or ⑤ dedifferentiation of well-differentiated carcinoma→ ⑥ invasion of the submucosa.