Tatsuya Kuzushima

Analysis of Oncogenes and Tumor Suppressor Genes in Human Breast Cancer

Oncogenes (c‐erbB‐2, c‐myc, and some genes linked to the 11q13 lesion), tumor suppressor genes (retinoblastoma gene, p53) and an antimetastatic gene (nm23/nucleoside diphosphate kinase) play important roles in breast cancer progression. Amplification of c‐erbB‐2, c‐myc, and int‐2, and expression of RB, p53 (mutant), and NDP kinase were determined in 77 primary breast cancer specimens. nm23‐H1 allelic loss was also studied. c‐erbB‐2 and c‐myc amplification, loss of RB expression, p53(mutant) expression, and nm23‐H1 allelic loss were also found in non‐invasive carcinoma, int‐2 amplification was significantly correlated with lymph node status (P=0.02) and a significant association was found between p53(mutant) expression and tumor size (P=0.04). c‐erbB‐2 amplification was strongly associated with disease‐free and overall survival in multivariate analysis (P=0.002). All of the c‐erbB‐2 amplified cases and all but one of the int‐2 amplified cases in node‐positive patients had relapsed within 2 years post resection. The cancer cells may acquire new proliferative pathways sequentially as a result of multiple genetic alterations which enable them to bypass the estrogendependent proliferation.

Clinical value of enzyme immunoassay of epidermal growth factor receptor in human breast cancer

SummaryEpidermal growth factor receptor (EGFr) levels were analyzed in 140 primary breast cancer specimens by immunohistochemical assay (ICA), competitive binding assay (BA), or enzyme immunoassay (EIA). Thirtynine of 118 specimens (33.1%) were scored as positive by ICA, 30 of 116 (25.9%: cut-off level 10 fmol/mg protein) by BA, and 31 of 80 (38.9%: cut-off level 5 fmol/mg protein) by EIA. Agreement on EGFr status was 72.3% (68/94) between ICA and BA, 77.0% (57/74) between BA and EIA, and 73.8% (59/80) between EIA and ICA. These discrepancies are based on assay differences and the heterogeneous distribution of cancer cells within specimens. Regardless of the assay method used, EGFr status had a significantly negative correlation with estrogen receptor status. Although EGFr-ICA and BA status had no relationship with prognosis, patients with medium and high EGFr-EIA level tumors (over 5 fmol/mg protein) had shorter relapse-free periods than those with low level tumors. However, the prognostic value of positive EGFr-EIA status was weaker than that ofc-erbB-2 overexpression.

Consecutively Occurring Multiple Fibroadenomas of the Breast Distinguished from Phyllodes Tumors by Clonality Analysis of Stromal Tissue.

We present a woman with consecutively occurring multiple fibroadenomas of the breast distinguished from phyllodes tumor by clonality analysis of stromal tissue. Fifty-three masses developed in her right breast in an 11.5 year period since first onset. A clonality analysis, performed by polymerase chain reaction (PCR), focused on theHpa II site within exon 1 of the androgen receptor (AR) gene. Estrogen receptor (ER) α immunohistochemistry was performed with a specific polyclonal antibody against the hormone binding domain of the protein. Since all of the nodules were polyclonal in stromal tissues, they were hyperplastic rather than true neoplasms such as phyllodes tumors. The co-existence of abundant adenosis foci and numerous sub-clinical small nodules in the adjacent breast tissue also suggested proliferative stimuli throughout the breast. ER α protein was expressed only in the nuclei of epithelial cells. The possible influence of ER positive epithelial cells on stromal cell growth is discussed.

Flow Cytometric Assay of c-erbB-2 Protein in Fine Needle Aspirates of Fresh and Frozen Human Breast Cancer Tissues

Using FCM (flow cytometry), we analyzed the ErbB-2 (c-erbB-2 protein) status of 61 breast cancer tissue samples obtained by FNAB (fine-needle aspiration biopsy). The number of cancer cells collected by FNAB from fresh samples was 1.7 ±0.7 × 105, 2.5 ± 0.6 × 105, and 4.0 ±0.8 × 105 by single, double and triple aspirations, respectively. A mean of 3.0 ± 0.6 × 105 cells was collected on three aspirations from frozen samples. The number of cells collected on three aspirations was sufficient for the measurement ofErbB-2. Cells with higherErbB-2 levels than those of normal human lymphocytes were designatedErbB-2 positive cells. The mean overall forErbB-2 positive cell rates was 20.5 ±27.9% (mean±SD). The rates were 27.9 ±31.6% in patients with recurrence and 15.9±24.4% in patients without recurrence. When the cut-off value was set at 20% of the positive cell rate (P=0.008, generalized Wilcoxon test), patients withErbB-2 negative tumors showed highly significantly longer survival without recurrence (P=0.008, generalized Wilcoxon test) and better overall survival rates (P=0.013) than patients withErbB-2 positive tumors. Among 61 specimens, 16 (26.2%) scored positive forErbB-2 by FCM. These finding indicated that the analysis ofErbB-2 status using FCM of samples obtained by FNAB should be useful for preoperatively evaluating the prognosis of patients with breast cancer.

A CASE OF EOSINOPHILIC GASTROENTERITIS CAUSING INTESTINAL OBSTRUCTION WITH ASCITES

症例は35歳,女性.腹痛と嘔吐を主訴に来院.精査にて腸閉塞と診断し,強い臨床症状を認めたため,同日,緊急手術を施行した.手術所見では腹水と,回腸末端より約210cm口側の部位で壁が肥厚狭窄し,これより口側で腸管が拡張していた.小腸部分切除術が施行され,腹水細胞診にて多数の好酸球と,切除された小腸の病理組織所見で全層性の好酸球浸潤を認め,好酸球性胃腸炎と診断した.好酸球性胃腸炎は消化管壁への好酸球浸潤を特徴とする比較的稀な疾患で,本邦報告例は現在まで120例あまりある.さらに手術例は調べ得た限り,自験例を含め32例と稀である.今回われわれは腸閉塞を来し,好酸球性腹水を伴った好酸球性胃腸炎の1手術例を経験したので若干の文献的考察を加え報告する.

A case of pancreatic ascites successfully treated with peritoneal lavage.

慢性膵炎に起因する膵性腹水の1例を報告した.患者は20年来アルコールを多飲していた39歳の男性で, 急激な腹部膨満と上腹部激痛で受診した.臨床所見と諸検査によって, 多量の膵性腹水とともに肝硬変と慢性膵炎が存在すると診断された.全身的療法の効果が乏しいことから, 発症16日目より腹膜灌流を開始した.メシル酸ガベキサート200mg, アミカシン100mgおよびヘパリン2,000単位を含む21の等張腹膜灌流液を腹腔内に60分で注入し, 引き続き120分で自然流出させた.この持続的腹膜灌流は3時間ごとに5日間連続しておこなった.この治療によって臨床症状, 血清アミラーゼをはじめとする検査結果は著しく改善した.すなわち, 蛋白分解酵素阻害剤を添加した等張の腹膜灌流液による連続的腹膜灌流力が有用であった.しかし, 腹膜灌流の時期と継続期間, 蛋白分解酵素阻害剤の種類と量, などなお考慮すべき点が残されている.

A case of superior mesenteric arterial occlusion successful treated with thrombectomy.

は じめ に 上 腸管膜 動脈 閉塞 症(以 下 本症)は 早期 診断 が困難 で,広 範 囲 な腸 壊死 に至 り開腹 され る こ とが多 く予後 は きわ めて不 良 とされ てい る1). わ れわ れ は腸切 除を 必要 とせず 血栓 除去 術 のみ で救 命 しえた70歳 男性 の1例 を経 験 した ので,当 院で経験 した5例 の本 症 と併せ て報 告す る. 症 例 患 者:70歳,男 性. 主 訴:上 腹 部痛. 家 族 歴,生 活歴:特 記す べ きこ とな し. 既 往 歴:昭 和61年9月 に心房 細動 と診 断 され,以 後 投薬 治 療 を うけてい る. 現病 歴:昭 和61年11月5日 午 後1時 半,突 然上 腹部 に激痛 を感 じ,食 物残 渣 を嘔 吐 した.た だ ちに救 急車 にて 当院緊 急入 院 とな った. 入 院 時 現 症:身 長165cm,体 重68kg,血 圧186/100 mmHg,脈 拍94/分 で不 整 であ り,眼 瞼結 膜 に貧血,眼 球 強膜 に黄 疸 を認め ず.腹 部 は軟 でやや 膨隆 して お り, 肝,脾,腫 瘤 を触知 しない.上 腹 部 に強 い 自発痛 と軽 度の圧 痛 を認 め るが,腹 膜刺 激症 状 は欠 いてい た.入 院2時 間 後 に は トマ トケチ ャ ップ様 の 血便 を 約300ml 認め た. 検査 成績:血 液生 化学 検査 で は 白血球 の軽 度 増多 お よび軽 度 の脱 水 を 認 め る 以外 は ほ ぼ 正常 で,GOT, GPT,CPK,LDHも 異 常 は なか った(表1).心 電 図 で は心房 細動 を認 め,腹 部 単純X線 写 真 では腸 管 ガ ス の増 加,鏡 面 像 な どの イ レウス所 見 は認 めな か った. 腹 部computed tomography(CT):腎 に嚢胞 を 腹 大動脈 に壁 の石灰 化を 認 めた.ま た確 定 診断後 に検 討