大腸sm癌の新しいsm浸潤度分類からみた組織異型度・発育先進部簇出像と脈管侵襲・リンパ節転移との相関

Correlation of Histological Atypia and Cancersprouting with Vascular Permeation and Lymph Nodal Metastasis by Our New Histological Classification of Submucosal Invasion by Colorectal Carcinomas

要旨　大腸sm癌の組織異型度（高分化腺癌は細胞異型度から高異型度と低異型度に分け，中・低分化腺癌は高異型度とした）と発育先進部簇出像が脈管侵襲やリンパ節転移とどのような相関を示すかを検討した．対象は，進行大腸癌を合併しない外科切除大腸sm癌151症例，154病変である（内視鏡摘除後の追加腸切除例を含む）．リンパ管の同定にはEGFR（epidermal growth factor receptor）抗体が血液型A型抗原に交叉反応し，リンパ管（ly検討例は76病変）の内皮細胞に陽性となることを利用した．簇出像の判定は今井の定義に従った．sm浸潤度分類はsm浸潤垂直最大長が500μmまでをsm₁，500＜X＜1,000μmをsm₂，1,000μm以上をsm₃と分類し，sm浸潤水平最大長が1mm以下をsm_a，1＜X＜3mmをsm_b，3mm以上をsm_cと分類した．低異型度sm癌13例ではsm浸潤度に関係なくly(－)，v(－)，n(－)で，簇出の頻度も23.1％と低かった．高異型度sm癌141例のうちsm₁癌12例は簇出の有無に関係なく，またsm水平浸潤度に関係なく，ly(－)，v(－)，n(－)であった．sm₂癌は2例（いずれもsm_2c）のみで，簇出(＋)50.0％，ly(－)，v(－)，n(－)であった．sm₃癌117例では，簇出(＋)が82.1％で，籏出(＋)と(－)との間で1y(＋)が72.1％vs．0％，v(＋)が40.2％vs．0％，n(＋)が22.5％vs．5.6％となり，前2者で有意差がみられた．更に，sm₃癌のうち，sm_3aの2例とsm_3bの5例はいずれも1y(－)，v(－)，n(－)であった．以上から，高異型度sm_3c癌で，発育先進部に簇出がみられる癌はly(＋)，v(＋)，n(＋)の可能性が高いこと，この簇出は通常のH・E標本ではしばしば同定が困難なly(＋)やv(＋)の指標として有用であることが示唆された．

　We studied 154 colorectal carcinomas, invading down to the submucosa, to evaluate the correlation of histological atypia and cancer-sprouting with vascular permeation and lymph nodal metastasis by our new histological classification of submucosal invasion. According to the criteria for cytologic grading by Watanabe et al, we divided well differentiated adenocarcinomas into two groups; cancers with low-grade atypia (CAL) and cancers with high-grade atypia (CAH). Moderately and poorly differentiated adenocarcinomas, and anaplastic carcinomas were grouped as CAH. Cancer-sprouting was defined as small cancer-cell nests composed of several cancer cells at the advancing margins in the submucosa. Venous permeation was verified by Victoria blue elastic fiber staining and lymphatic permeation by EGFR-immunostaining which shows cross-reaction for lymphatic endothelium of blood group A and AB patients. The grade of submucosal invasion was designated as follows: sm₁; X≦500μm, sm₂; 500＜X＜1,000μm, and sm₃; X≧1,000μm by vertical length of cancer tissue in the submucosa, and sm_a; X≦1mm, sm_b; 1＜X＜3mm, and sm_c; X≧3mm by horizontal length of cancer tissue in the sumucosa.

　None of the CALs (n=13) regardless of grade of submucosal invasion, and the sm_l,2-CAHs (n=14) showed either vascular permeation or lymph nodal metastasis (Table1, 2). In the sm₃-CAHs (n=117) cancer-sprouting was positively related to vascular permeation (venous permeation; 40.2% vs. 0%, p＜0.0002, lymphatic permeation; 72.1% vs. 0%, p＜0.001) and lymph nodal metastasis (22.5% vs. 5.6%) (Table3). All of the sm_3a-CAHs (n=2) and sm_3b-CAHs (n=5), however, were negative for vascular permeation and nodal metastasis.

　These results indicate that the histological atypia of colorectal cancers and their sprouting are useful parameters for predicting vascular permeation and lymph nodal metastasis, and that submucosal carcinomas of CAL or sm_1,2-CAH or 94% of sm₃-CAH without cancer-sprouting at the advancing margins do not need further surgery after endoscopic resection.