Yoshihiro Kagawa

Multiple Genetic Alterations and Abnormal Growth Factor Network in Human Esophageal Carcinomas

Esophageal carcinoma is the most malignant gastrointestinal neoplasm. Multiple genetic alterations of oncogenes and tumor suppressor genes take place in esophageal squamous cell carcinomas. Co-amplification of cyclin D1, hst-1, and int-2 gene is found in 40% of the primary tumors and almost all metastatic tumors. The prognosis of the patient with gene amplification is evidently poorer than those without amplification. Multiple alterations of tumor suppressor genes and negative cell cycle regulators, including p.53 gene, Rb gene, BRCA1 gene, p16 (MTS1), p15 (MTS2), and p21 (WAF1/CIP1), play an important role in the development and progression of esophageal carcinomas. Furthermore, multiple growth factor—receptor loops exist and participate in the autocrine growth of the esophageal cancer. They include epidermal growth factor (EGF), transforming growth factors (TGF) a and β, and platelet-derived growth factor (PDGF). Overexpression of EGF, TGF-α, and EGFR is closely correlated with the malignant behavior of tumor cells and patient prognosis. These growth factors stimulate production of the interstitial degradation enzymes and down-regulation of Ecadherin function, which may lead to cell invasion and metastasis.

Angiosarcoma of the breast: Report of a case and autopsy findings

We report a case of angiosarcoma of the breast and the autopsy findings. The patient was a 35-year-old premenopausal woman who complained of a tumor in her left breast. We found a tumor measuring 55 mm in diameter in the lower external quadrant. The tumor was elastic and soft, smooth surfaced, well-defined and mobile. Dimpling sign or change of skin color were not observed. Clinically it was diagnosed as phyllodes tumor, but tumorectomy revealed primary angiosarcoma of the breast. Further extended surgery was recommended, but the patient refused additional therapy. Histological findings revealed a free surgical margin and neither lymph node metastasis nor distant metastasis were clinically observed. Seven months later, local recurrence in the same breast was recognized and finally radical mastectomy was carried out. Histological findings showed recurrence of angiosarcoma in the left breast but lymph node metastasis was not detected. Two months after mastectomy, metastases to the cervical and thoracic vertebrae were observed and radiation therapy was performed. Sixteen months from onset, she died due to multi-organ failure as general metastases of angiosarcoma. At autopsy, metastases to many organs including the digestive system were observed. The incidence of primary angiosarcoma of the breast is low but its prognosis is poor. This case emphasized the difficulties in clinical diagnosis and treatment for the angiosarcoma of the breast.