The Correlation of Serum HER-2/neu and CA15-3 in Patients with Metastatic Breast Cancer / 한국유방암학회지

PURPOSE: The extracellular domain (ECD) of the HER-2/neu oncoprotein, whose molecular weight is the range from the 95 kD to 105 kD, is shed into the blood from the cell surface via, proteolysis by a metalloprotease. A monoclonal antibody immunoassay has been developed for measuring the circulating concentrations of serum HER-2/neu ECD (following serum HER-2/neu). Serum HER-2/neu has been reported to be correlated with an increased tumor volume in those patients suffering with breast cancer. We measured the serum CA15-3 level, which is a surrogate marker of the tumor burden, we analyzed the correlation of the serum CA15-3 with the serum HER-2/neu and we analyzed the association of both markers with the clinical outcomes. METHODS: The sera for the analysis of both HER-2/neu and CA15-3 were obtained from 99 healthy Korean women, 66 primary breast cancer patients and 43 metastatic breast caner patients. The serum HER-2/neu level was measured quantitatively with using an ADVIA Centaur(R) automated immunoassay analyzer (Bayer Health Care LLC, Diagnostics Division, Tarrytown, New York, USA) and the CA 15-3 level was measured via radioimmunoassay. RESULTS: The serum HER-2/neu level was increased 23 metastatic cancer patients (53%). On the analysis of the correlation of serum HER-2/neu and CA15-3, the correlation coefficient (r) was 0.8072. Thus a positive serum HER-2/neu test in breast cancer patients was highly associated with the CA15-3 level for assessing whether metastasis was present or not. For the relationship between primary breast cancer and metastatic breast cancer, the former was classified as the control group and the latter as the patient group. The results of the Receiver Operation Characteristic (ROC) curve for serum HER-2/neu and CA15-3 showed no statistically significant differences (p=0.176) but the diagnostic efficacy of the serum HER-2/neu test was measured more exactly than that of CA15-3 and CA15-3 a tool for measuring a tumor marker for the diagnosis of whether metastasis was present or not. CONCLUSION: Serum HER-2/neu is a significant independent predictive prognostic factor for metastatic breast cancer patients. In view of the results we have achieved so far the serum HER-2/neu level in metastatic breast cancer patients may play an important roll as an independent tumor marker.

Expression of HER-2/neu and Paxillin in Ductal Carcinoma in situ, Invasive Ductal Carcinoma with Ductal Carcinoma in situ and Mucinous Carcinoma / 한국유방암학회지

PURPOSE: We purpose to determine the correlation of HER-2/neu and paxillin expression in ductal carcinoma in situ (DCIS), invasive ductal carcinoma with ductal carcinoma in situ (IDC with DCIS) and mucinous carcinoma. METHODS: To evaluate the expression of HER-2/neu and paxillin, the immunohistochemical staining was performed for 13 cases of DCIS, 13 cases of IDC with DCIS and 6 cases of mucinous carcinoma. RESULTS: The DCIS and IDC were associated with infiltration of the inflammatory cells, especially in the comedo type and solid type of tumor. In cases with infiltration of the inflammatory cells, HER-2/neu and paxillin were strongly expressed. When comparing the expression level of HER-2/neu from adjacent normal tissue between DCIS and IDC with DCIS, expression of HER-2/neu was similar to that of normal tissue adjacent to DCIS. However, in the adjoining normal ductal epithelial cells, paxillin was highly expressed in cells of all of the tumor types, and especially for IDC with DCIS. HER-2/neu and paxillin were not expressed in mucinous carcinoma cells in all cases. CONCLUSION: HER-2/neu in the DCIS and IDC with infiltration of inflammatory cells shows higher expression than non-inflammatory DCIS and IDC. If normal duct epithelial cells show a high level of HER-2/neu expression, the epithelial cells have a high probability of transformation into anaplastic cells. However, paxillin appears to have no value as a prognostic factor. The difference of expression of HER-2/neu between IDC with DCIS and DCIS suggests a different origin of tumor cells. The growth pattern of mucinous carcinoma cell is different from the that of DCIS or IDC cell, which grow slowly.

Prognostic Value of Apoptosis and the Survivin, bcl-2, and p53 Expressions in Breast Cancer Patients / 한국유방암학회지

PURPOSE: Survivin is a member of the inhibitor of apoptosis (IAP) protein family, and it is involved in the regulation of cell division. The over-expression of survivin has been reported to be associated with the parameters for a poor prognosis in most human cancers, including lung, breast, colon, stomach, esophagus, pancreas, etc. In this study, we examined the expression of a member of a novel IAP protein family, survivin, in breast cancer and its association with tumor cell apoptosis and the overall prognosis. METHODS: 80 cases of formalin-fixed paraffin-embedded breast cancer tissue were immunostained with, using polyclonal survivin (Novus Biologicals, Littleton, USA), monoclonal bcl-2 (DAKO, Carpinteria, USA), and monoclonal p53 antibodies (DAKO, Carpinteria, USA). The histochemical method used for the analysis of apoptosis was based on ApopTag. Peroxidase In Situ OligoLigation (ISOL) Apoptosis Detection Kit (CHEMICON International Inc. Temecula, USA). RESULTS: Immunohistochemical analysis showed that cytoplasmic survivin expression was positive in 43 of 80 cases (53.8%) of breast carcinomas and it was positive for 70% of the cases that showed a bcl-2 expression tumors. Statistical analysis revealed that the survivin expression was correlated with lymph node metastasis, the tumor stage, and the histological grade. Although the survivin expression was not correlated with p53 mutations, the survivin positive cases were associated with a bcl-2 expression (p=0.015) and a reduced apoptotic index (p=0.024). On the Cox proportional hazard model analysis, the apoptotic index was not identified as a significant independent predictor of overall survival (p=0.072), although the patients with a low apoptotic index ( or =0.2%). CONCLUSION: The results suggest that apoptosis inhibition of apoptosis by survivin may be a prognostic parameter for a worse outcome in breast carcinoma patients.

Inhibitory Effect on Angiogenesis of a Selective Cyclooxygenase-2 Inhibitor with using Mouse Mammary Tumor cells / 한국유방암학회지

PURPOSE: Angiogenesis plays a key role in the growth and metastasis of malignant tumor. Angiogenesis is reportedly enhanced by prostaglandins (PGs). Cyclooxygenase (COX)-2 is an inducible enzyme that catalyzes the formation of PGs from arachidonic acid. The COX enzyme system is composed of two isoenzymes, COX-1 and COX-2. Recent sources of experimental and epidemiological evidence suggest a significant role for the COX enzymes, particularly COX-2, in the pathogenesis of breast cancer. COX-2 overexpression in a murine mammary gland is sufficient to cause tumor formation. We performed our study to determine the effect of COX-2 inhibitor in a in vivo mouse mammary tumor (MMT) cell line. METHODS: In order to test our study, 24 C57BL/6 type mice (Jackson Laboratory, Bar Harbor, USA) were randomized to receive 35 days of either placebo supplemented diet (n=11) or a 1,500ppm celecoxib (CELEBREX, Pfizer Inc. St. Louis, USA) supplemented diet (n=13) beginning at day 0. At 14 days after the beginning day, 30 microliter of a 1% India ink solution that contained 500,000 of MMT cells or dye alone (control) was intradermally inoculated at each flank (day 14). The animals were sacrificed 21 days later (day 35) and skin specimens were harvested/processed for quantification of the microvessel density (MVD) that was associated with each inoculated site. The aortas that were isolated according to each treatment group at the time of animal sacrifice were used to create identical aortic ring angiogenesis assays (media 199 supplemented with 20% FBS). Explants were evaluated for 14 days in culture to determine both the rate of angiogenesis initiation (% of explants exhibiting the angiogenic phenotype) and the neovessel growth rate (using a subjective angiogenic index score for the wells exhibiting initiation). Analysis of variance (ANOVA) was used to evaluate the differences between groups for each assay. RESULTS: According to the immunohistochemical staining, celecoxib administration resulted in a parallel decrease in the MVD at both the control and MMT inoculated sites (22% and 21%, p = 0.025 and p = 0.010 respectively). On the aortic ring assay, the dietary treatment group was not significantly inhibited compared with the placebo group (75% and 63.3%, respectively, p = NS). However, dietary celecoxib administration significantly inhibited the angiogenic index of the neovessel growth rate (5.0 +/- 2.38 and 8.9 +/- 3.44, respectively, p < 0.001). CONCLUSION: These results suggest that a selective COX-2 inhibitor had an antiangiogenic effect on the in vivo tumor cells. We will perform more investigations of a selective COX-2 inhibitors, and these may will be crucial drugs to use as new chemotherapy agents for treating in cancer.

Treatment of Breast Fibroadenoma with Interstitial Laser Photocoagulation / 한국유방암학회지

PURPOSE: Hyperthermia treatments (Laser, Macrowave, Microwave, Electromagnetic force, and Ultrasonic heating system etc.) haves been used for the purpose tof destroying the focus part of tumors. Interstitial Laser Photocoagulation (ILP), originally attempted by Bown in 1983, experimentally makes use of Nd:YAG Laser in breast cancer. This study attempted to evaluate the effect of ILP for the fibroadenomas of the breast under the local anesthesia. METHODS: From the physical examination findings, breast ultrasonogram, mammogram and Fine Needle Aspiration Cytology of 74 unmarried women patients, diagnosed as having a fibroadenoma, which is a breast benign tumor, who took ILP treatment and could be followed up based on their medical records 62 were examined and analyzed. After checking the accurate positioning of the optical fiber in the tumor, through an ultrasonogram under the local anesthesia, the ILP treatment was conducted using a Diode Laser (Diomed(r) Ltd.). RESULTS: The average age of the patients was 23 years, and the mean sizes of the tumors were as 1.6 and 1.8 cm on physical examination and 1.8 cm on the ultrasonogram, respectively. There were significant decreases in the clinical and sonographic sizes following the treatment (P<0.05, P<0.01). From a comparison of the tumor sizes before and after the ILP treatment, the tumor reduction rates from the physical examination and ultrasonogram findings were 92 and 80%, respectively, when the size of the tumors was below 1 cm, and the disappearance rates were 92% and 80%, respectively, when the size of the tumors was below 1 cm. CONCLUSION: Interstitial laser photocoagulation is a safe, precise, minimally invasive, and cosmetic procedure for the in situ destruction of breast fibroadenomas.