Yukashi Itoh

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.

Recurrent breast cancer at 21 years after resection detected by serum tumor markers and manifested as dermatomyositis

A 52-year-old Japanese woman developed dermatomyositis. She had undergone a standard radical mastectomy for left breast cancer 21 years earlier. Though no physical sign of recurrent breast cancer appeared clinically, levels of tumor markers were abnormally elevated. Therefore, tamoxifen and CAF therapy were given. Further, the clinical course of dermatomyositis almost paralleled the level of serum tumor markers and the clinical course of her recurrent breast cancer. These markers were useful for detecting the recurrence, following the metastatic disease, and monitoring her response to therapy.

Readministration of tamoxifen after adjuvant therapy for recurrent breast cancer.

BackgroundPrevious series concerning tamoxifen (TAM) rechallenge did not obtain satisfactory results. Using stricter criteria, we now assess the usefulness of readministration of TAM as an initial therapy for patients with recurrent breast cancer.MethodThe eligibility criteria were postmenopausal, estrogen receptor (ER) positive or unknown, at least 12 months of adjuvant TAM, a 6-month or longer drug-free period and no previous therapy after recurrence. A total of 10 patients were enrolled. TAM was administered in daily doses of 20 or 30 mg.ResultsThe mean age of the patients at the time of recurrence was 64.8 years. The receptor status was positive in 8 patients and unknown in 2. The median disease-free interval (DFI) after mastectomy was 71.7 months. A complete response was observed in one patient, a partial response in 6, stable disease in 2, and progression in one. The response rate was thus 70%, with an additional two patients showing no progression over 6 months. Although only one patient with a DFI of less than 48 months showed a positive response, all patients with a DFI longer than 48 months showed a clinical response. The duration of response was less than 12 months in 3 patients and longer in 4.ConclusionThe post-adjuvant readministration of tamoxifen is a useful first choice therapy for postmenopausal recurrent breast cancer patients with positive ER and longer DFI.

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 Leiomyoblastoma Originated in the Duodenum.

平滑筋芽細胞腫は胃に発生する場合がほとんどで, 十二指腸原発例は少ない.今回, 我々は72歳の女性の十二指腸下行脚に発生した平滑筋芽細胞腫の1例を経験した.十二指腸原発平滑筋芽細胞腫の本邦報告例は過去に22例しかなく, このうち悪性症例は4例で, 1例のみ腫瘍死が確認されている.本症例は, 膵頭十二指腸切除術を施行し, 手術所見や組織学的検索で浸潤傾向やリンパ節転移など悪性所見を認めなかったが, 術後約4年で, 肝転移, 腹水貯留をきたし死亡した.また, 本腫瘍は通常, 類上皮性平滑筋腫瘍と同義語として取り扱われている.しかし, HE染色を中心とした通常観察では, 神経原性腫瘍との鑑別が困難な症例もあり, 本症例でも, 免疫染色によりこの鑑別が可能であった.本腫瘍の組織学的診断に際しては, 通常観察で典型例と判断されても, 免疫染色や電顕を使用した多角的検索により, 平滑筋由来であることを確認する必要があると考えられた.