Reduced Expression of p27 Correlates with High Grade Malignancy and is Associated with Poor Clinical Outcome in Human Greast Cancer / 대한암학회지

PURPOSE: The cyclin-dependent kinase inhibitor p27Kipl is a negative regulator of cell proliferation. Its expression is known to be altered in proteasome-dependent manner without changes in DNA level. Reduced expression of p27Kipl is associated with aggressive behavior in a variety of human cancers. We investigated expression of p27Kipl protein in human breast cancer using immunohistochemistry to assess its biologic implication along with cell cycle analysis by flow cytometry. MATERIALS AND METHODS: We peformed immunohistochemical assay for expression of p27 in total 68 patients with invasive ductal cancer along with 27 benign ductal hyperplasia and 10 ductal carcinoma in situ. The data were analyzed in association with proliferative activity of the same tissues and biologic parameters. RESULTS: In epithelial cells of normal and benign breast disease, expression of p27Kipl was well preserved while its expression markedly decreased in breast cancer (45 of 68). Expression of p27Kipl was significantly reduced in poorly differentiated cancers and in advanced stage of the disease. Levels of p27Kipl expression correlated with cell populations in GO/Gl phase of the cell cycle. In survival analysis, p27Kipl was useful to predict disease-free survival but not overall survival of the patients after adjuvant chemotherapy. CONCLUSION: p27Kipl seems to have a role in cell proliferation and differentiation process during carcinogenesis of breast cancer. The results of present study suggest that p27Kipl can be used in predicting response to systemic chemotherapy in a subset of patients with breast cancer.

Change of Mad1 Expression in Human Breast Cancer and Normal Breast Tissues / 대한암학회지

PURPOSE: Madl protein is known to directly repress Myc target genes and antagonize Myc function. Consequently, Madl is considered to function as a tumor suppressor. We undertook this study to investigate the regulatory effect of Madl on cancer progression in human breast cancer. MATERIALS AND METHODS: We performed immunohistochemical assay for Madl protein together with Myc in human breast cancer as well as tissues from normal and benign diseases. The protein assay data were evaluated together with clinical and biologic parameters of the patients. RESULTS: Of 66 patients with invasive ductal cancer, Madl expression was detected in 22 patients (33.3%) with breast cancer. Intensity and area of Madl expression significantly decreased in DCIS and invasive cancers, while high levels of Madl expression were persistent in benign breast lesions. Madl expression was significantly reduced in poorly differentiated tumors (p=0.0002). Expression of Madl was not associated with size of the tumors, lymph node status, and stage of the disease. We could not observe any correlation between S-phase and expression status of Myc or Madl. Madl expression was closely linked to differentiation of the cancer cells and inversely correlated with Myc expression (p=0.042). In survival analysis, Madl possessed a prognostic significance in predicting recurrence of the disease but not overall survival after CMF chemotherapy. CONCLUSIONS: In human breast cancer cells, expression of Madl seems to be downregulated while expression of Myc is amplified. Altered expression of Mad1 may play a role in malignant transformation of human mammary epithelial cells and represent an aggressive phenotype in human breast cancer.

Correlation between Proliferative Index by DNA Flow Cytometry and Histological Features in Stomach Cancer / 대한암학회지

PURPOSE: Stomach cancer is the most prevalent malignancy in Korea. The survival rate in advanced stage disease has stayed in less than 50%. One of the possible explanation for dismal outcome of stomach cancer is various biologic behavior of cancer cells of heterogeneous clones. Introduction of flow cytometric analysis has provided objective information of cancer cell kinetics, and it could help us in deciding the appropriate adjuvant therapy. The prospective study was undertaken to evaluate the clinical implication of DNA ploidy and each proliferative fraction by DNA flowcytometry. The other aim of the study was to evaluate which one is the most valuable index for proliferative activity of cancer cells. MATERIALS AND METHODS: One hundred and fifty-four patients who underwent gastric resection for primary stomach cancer were included in this study. Male to female ratio was 2.1: 1, and mean age was 58.2 years (range: 26-81). Resected cancer tissues were immediately transported to the flow cytometry laboratory, and analyses for DNA content and cell cycle distribution were carried out by FACScan. The results of flow cytometric analysis were studied in correlation with clinical and histologic parameters; depth of invasion, lymph node metastasis, distant metastasis, stage, Laurens classification, histologic types and grade. RESULTS: The frequency of aneuploid cancer was 40.3% (62 cases). The mean value of GO/Gl fraction was 75.9% and that of S-phase was 16.0%. Decrease of GO/Gl correlates with lymph node metastasis (p 0.015) and stage (p-0.046). Aneuploid cancer exhibited significant decrease of GO/Gl fraction. However, there was no significant conelation between decreased GO/Gl and depth of invasion, distant metastasis, Laurens classi- fication, differentiation of the cancer cells. Patients with metastasis to the lymph node or distant organs had increased S-phase fraction (p-0.032). High S-phase fraction also correlates with advanced stage (p-0.011) and ploidy of the oancer cells (p=0.001). When the ploidy of the tumor was analysed with clinical variables, aneuploid pattern was increased in cancer cells with intestinal type according to Laurens classificatian (p=0.042), Diploid cancer had significantly lower level of S-phase fraction than aneuploid cancer (p 0.001). CONCLUSION: Ploidy and growth fraction of the stomach cancer reflected the extent of disease in different aspects. However, there was no single parameter which reflected the extent of disease and degree of malignant potential. Furthermore, there is a possibility that S-phase & action alone is not an accurate parameter for the proliferative activity of stomach cancer cells. In conclusion, flow cytometric analyses is a valuable study providing us more precise information about biologic properties of cancer cells. However, further evaluation with longer follow-up period is imperative because the ultimate value as an prognostic factors can be estimated in respective of clinical outcomes.

Fatal Doudenal Ulcer Bleeding in Status Asthmaticus Treated with Theophylline and Steroids

It is generally agreed that theophylline preparations and steroids should be given intravenously for status asthmaticus. Theophylline can potentially have adverse gastrointestinal effects including abdominal pain, nausea, vomiting, and hematemesis. Upper gastrointestinal bleeding in patients treated with corticosteroids without a past history of upper gastrointestinal bleeding has been reported rarely. But the etiologic significance of the stress of status asthmaticus, administration of theophylline or corticosteroids in the development of ulcer has been open to question. We report a case of 8-year-old boy with status asthmaticus treated with these medications and later found to have a bleeding duodenal ulcer for which emergency surgery was necessary.