Histopathologic Change Of Breast Cancer Caused By Preoperative Chemotherapy And Its Molecular Mechanism

Breast cancer is a. common malignant tumor for women. Surgical treatment is a major means of the synthesized treatment strategies for this tumor. Since 197O's,preoperative chemotherapy has been applied to breast cancer. This application has been proved to be effective in decreasing the primary tumor size and killing the metastatic cells. Thus, it improves the survival rate of patients with breast cancer. Usually patients with breast cancer are given no less than three cycles of chemotherapy abroad. Then operation is planned within three weeks of the last primary dose. In our hospital, patients with breast cancer (mostly stage II) are given chemotherapy dose once in about two days before operation. Drug regimens are usually CMF (Cyclophosphamide,methotrexate and 5-fluorouracil) or CAF (5-fluorouracil,Adriamycin and cyclophosphamide).This provides us a model for studying the early effects of chemotherapeutic agents on tumor cells in vivo. In the specimens obtained after operation, we observed some pathological changes induced by chemotherapeutic agents, such as the malignant cells becoming enlarged with vacuolated cytoplasm and vesicular nuclei with prominent nucleoli. These features are interpreted as degeneration in nature. Local necrosis was also seen. Occasionally the nuclei were angular and 4 hyperchromatic. However,it is unclear whether these alterations play a predictive value in the estimation of chemosensitivity. And the molecular mechanism of these histopathologic alterations is also unclear. Telonierase is a new tumor marker and is suggested as a potential therapeutic target by some researchers. Some studies in vitro also showed that chemotherapeutic agents could inhibit telomerase activity of tumor cells. For example, telomerase activity was inhibited by 5-fluorouracil in MCF-7 cells;Telomerase activity was also inhibited by cisplatin in liver cancer cells and testicular cancer cells. Some other researchers have suggested that telomerase can be a marker of cell survival and be used in the chemosensitivity study in vitro.They have found that there is a direct proportion between the telomerase activity and the logarithm value of the total tumor eel] number measured in less than one thousand. So they suggest that decline in telomerase activity can reflect the efficiency of tumor cells killed by antineoplastic agents in vitro. The p.53 gene is an important tumor suppressor gene. It correlates with DNA replication and repair. It also relates to apoptosis of normal cells. The mutated p53 gene is involved in tumorigenesis and drug resistance. Recently the induction of apoptosis has been regarded as part of the important mechanism of antineoplastic activities of chemotherapeutic agents. The bcl-2 gene is an important anti-apoptotic gene which is involved in some apoptotic processes induced by chemotherapeutic agents. Purpose To study the histopathological change caused by preoperative chemotherapy and its molecular mechanism. Materials and methods We determined the expression of P53 and Bcl-2 protein with the 5 streptavidin-peroxidase immunohistochemistry in 113 cases of formalin-fixed paraffin-embedded breast cancer tissues collected from 1998 to 2001 in second hospital of medical school of Zhejiang Universi...