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The Relationship between Plasminogen Acti- vator Inhibitor-1 and Bone Marrow Microme- tastases in Breast Cancer.

Jung Han YOON ; Young Jong JAEGAL ; Soon Pal SUH

Journal of Korean Breast Cancer Society.2001;4(2):192-197. doi:10.4048/jkbcs.2001.4.2.192

PURPOSE: Plasminogen Activator Inhibitor-1 (PAI-1) is the principal physiological urokinase-type plasminogen activator and is thought to regulate the overall invasive and metastatic behaviors of cancer cells. Although the occurrence of bone marrow micrometastases is an independent prognostic factor in breast cancer, its pathomechanism is not yet fully revealed until. We hypothesize that PAI-1 has a major role in the development of bone marrow micrometastases in breast cancer. Accordingly, we attempted to establish a correlation between PAI-1 activity in tumor tissues and bone marrow micrometastases in breast cancer. Additionally, we studied the relationship between PAI-1 level and selected clinicopathological characteristics such as tumor size, lymph node metastases, and steroid receptor positivity. METHODS: we used the RT-PCR targeting mRNA of cytokeratin 19 to detect bone marrow micrometastases and an ELISA kit to estimate PAI-1 activity in frozen tumor tissues. RESULTS: (1) The median PAI-1 level was 13.55 ng/ml+/- 16.38 in the cases with bone marrow metastases, and 6.02 ng/ml+/-10.85 in the cases without bone marrow micrometastases. The difference was statistically significant (p-value= 0.0165). (2) PAI-1 levels did not show any significant differ-ences according to lymph node status, variation of tumor size or the expression status of the steroid receptors. CONCLUSION: PAI-1 is considered to have a role to hematogenous metastases of breast cancer cells. However, further study is recommended to reveal its significance as an independent prognstic factor for breast cancer.
Bone Marrow* ; Breast Neoplasms* ; Breast* ; Enzyme-Linked Immunosorbent Assay ; Keratin-19 ; Lymph Nodes ; Neoplasm Metastasis ; Neoplasm Micrometastasis ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Plasminogen* ; Receptors, Steroid ; RNA, Messenger ; Urokinase-Type Plasminogen Activator

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The Significance of Cytokeratin-20 Detection in Peripheral Blood and Bone Marrow of Breast Cancer Patients.

Youn Ki MIN ; Namryeol KIM ; Seok Hyung KANG ; Seong Jin CHO ; Han Kyeom KIM ; Jeoung Won BAE ; Bum Hwan KOO

Journal of Korean Breast Cancer Society.2001;4(2):185-191. doi:10.4048/jkbcs.2001.4.2.185

PURPOSE: It is very important to detect hematogenous spread of cancer cells early in breast cancer patients in order to properly determine the prognosis and adjuvant therapy. In this study, we attempted to detect Cytokeratin-20 (CK-20) as a mRNA marker of cancer cells in peripheral blood and bone marrow using the reverse transcriptase-polymerase chain reaction (RT-PCR). METHODS: We obtained peripheral blood and bone marrow from 41 breast cancer patients who had been treated by Korea University Hospital. Using the RT-PCR method, we detected the CK-20 and compared the positive detection rate and concordance rate between two sources. Furthermore, we analysed the correlation with other known prognostic and predictive factors. RESULTS: The CK-20 detection rate was 36.5% in peripheral blood and in bone marrow. The concordance rate between both sources was 56%. In CK-20 detection, there was no significant correlation seen between peripheral blood and bone marrow (p>0.05). Additionally, there were no statistically significant correlations found between the other predictive factors (ER, PR, p53 protein expression, nm23 protein expression). Six cases who were CK-20 positive and were detected in both (peripheral blood, bone marrow) source showed advanced stage and axillary lymph node metastasis (p<0.05). CONCLUSION: The detection of CK-20 in peripheral blood and bone marrow correlated with stage and axillary nodal status. Therefore, this may suggest poor clinical prognosis if CK-20is detected in both sources in a breast cancer patient. The RT-PCR assay for detection of CK-20 is a very sensitive method, however the standardization and quality control of the RT-PCR method are important and multi-center trials are required.
Bone Marrow* ; Breast Neoplasms* ; Breast* ; Humans ; Keratin-20* ; Korea ; Lymph Nodes ; Neoplasm Metastasis ; Neoplasm Micrometastasis ; Prognosis ; Quality Control ; RNA, Messenger

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Jeong Soo KIM ; Kee Hwan KIM ; Chang Hyeok AHN ; Hae Myung JEON ; Sang Seol JUNG ; Seock Ah IM

Journal of Korean Breast Cancer Society.2001;4(2):179-184. doi:10.4048/jkbcs.2001.4.2.179

PURPOSE: In order to confirm the clinical application of a tissue microarrays method, the expression rate and relationship between factors related apoptosis, hormonal receptors and the clinical factors were investigated. METHODS: A tissue microarrays of 59 breast cancer tissues, and apoptosis related factors were examined by immunohistochemical staining using monoclonal antibodies. RESULTS: The median age of the patients was 49.9 years and 86.4% had a pathological stage of over stage II. The average number of metastatic lymph nodes was 3.8. p53 expression was noted in 21 cases (35.6%) and was related to Bcl-2, ER and PR expression. PTEN was expressed in 39 cases (66.1%) and related to FAS, Bcl-2, ER and PR expression. Fas was expressed in 34 cases (57.6%) and related with PR and BAX expression. BAX expression was observed in 42 cases (71.2%) and was related to the metastatic axillary lymph nodes, and both Bcl-2 and PR expression. Bcl-2 expression was noted in 33 cases (55.9%) and related to ER and PR expression. ER was expressed in 34 cases (57.6%) and was related positively with PR expression. CONCLUSION: The tissue microarrays method can be used for both screening and analyzing many factors or different tumor types. This new technique may be very powerful for the rapid identification of the tumor characteristics.
Antibodies, Monoclonal ; Apoptosis* ; Breast Neoplasms* ; Breast* ; Humans ; Lymph Nodes ; Mass Screening

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Relationship between Cathepsin D Expression and Other Prognostic Factors in Primary Breast Cancer.

Woo Jin CHUNG ; Dong Eun PARK ; Kwang Man LEE ; Kwon Mook CHAE ; Ki Jung YOON

Journal of Korean Breast Cancer Society.2001;4(2):172-178. doi:10.4048/jkbcs.2001.4.2.172

PURPOSE: Cathepsin D, a lysosomal protease has been proposed to play a role in the local invasion and metastatic dissemination in primary breast cancer. Although there are many conflicting results, the overexpression of cathepsin D has been considered to be related with a poorer prognosis of breast cancer. This study was designed to verify whether cathepsin D expression is related to other prognostic factors in breast cancer. METHODS: Cathepsin D was assessed by immunohistochemistry using murine monoclonal anti-cathepsin D antibody (ZyMED) in 79 paraffin-embedded primary breast cancer specimens. Cathepsin D expression was compared to other prognostic parameters such as tumor size, axillary lymph node metastasis, tumor histologic grades, hormone receptors (ER & PR), p53, c-erb B2, Ki-67, MVD (microvessel density), and Pgp (P-glycoprotein). RESULTS: A high-expression of cathepsin D was found in 35 of 79 patients (44.3%) with primary breast cancer. Cathepsin D expression was not related to tumor size, axillary lymph node metastasis, tumor histologic grades, hormone receptors, p53, Ki-67, or CD31. However, a significant relationship was found between cathepsin D expression and c-erb B2 (p=0.007), and between cathepsin D expression and Pgp (p=0.003). CONCLUSION: These results suggest that cathepsin D expression may be an indicator of a poor prognosis in breast cancer. However, further studies are required to verify the xact role of cathepsin D in the prognosis of breast cancer.
Breast Neoplasms* ; Breast* ; Cathepsin D* ; Cathepsins* ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis

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Prognosis of GLUT1 Expression in Human Breast Carcinoma.

Hyung Joon AHN ; Kil Yeon LEE ; Sang Mok LEE ; Suck Hwan KOH ; Sung Wha HONG ; Soo Myung OH ; Youn Wha KIM

Journal of Korean Breast Cancer Society.2001;4(2):167-171. doi:10.4048/jkbcs.2001.4.2.167

PURPOSE: An increase of glucose uptake and glycolytic metabolism has been reported in malignant cells as compared with normal cells and tissues. We hypothesized that human erythrocyte glucose transporter-1 (GLUT1) expression is increased in breast carcinoma and may be correlated with long term clinical outcome. METHODS: Two hundred ninety formalin fixed, paraffin embedded sections of infiltrating ductal carcinomas of the breast were immunostained with anti-GLUT1. RESULTS: Among the known clinicopathological prognostic factors, GLUT1 expression was correlated positively with histological grade (p=0.000) and tumor size (p=0.003). In a multivariate analysis, lymph node involvement and GLUT1 expression were statistically significant prognostic factors. The cummulative survival rates of GLUT1 expression and LN involvement were statistically significant (p=0.0061, p=0.0009) respectively. Our results suggest that 1) GLUT1 expression is correlated with histological grade and tumor size, and 2) GLUT1 expression correlates with a poorer prognosis in patients with infiltrating ductal carcinoma of the breast. CONCLUSION: The results of our study suggest that immunohistochemical staining of GLUT1 expression is strongly associated with neoplastic progression in breast carcinoma, and that GLUT1 expression has value in estimating the prognosis of patients with breast carcinoma.
Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Erythrocytes ; Formaldehyde ; Glucose ; Humans* ; Lymph Nodes ; Metabolism ; Multivariate Analysis ; Paraffin ; Prognosis* ; Survival Rate

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Aromtase Inhibitors in Breast Cancer.

Woo Shin SHIM

Journal of Korean Breast Cancer Society.2002;5(4):323-337. doi:10.4048/jkbcs.2002.5.4.323

No abstract available.
Breast Neoplasms* ; Breast*

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Prognostic Significance of Hormonal Receptors in Very Young Women with Early Breast Cancer.

Woo Chan PARK ; Kwan Su SUNG ; Jeong Soo KIM ; Se Jung OH ; Seung Hye CHOI ; Young Kyoung YOU ; Hea Myung CHUN ; In Chul KIM ; Sang Seol JUNG

Journal of Korean Breast Cancer Society.2002;5(4):319-322. doi:10.4048/jkbcs.2002.5.4.319

PURPOSE: The prognosis of breast cancer in very young women is generally considered to be unfavorable. In addition, younger patients (<35 years) with estrogen- receptor (ER) positive tumor had shown a significantly worse disease- free survival than younger patients with ER negative tumors. To confirm the prognostic effects of ER on the survival in very young Korean women with early breast cancer, we performed a retrospective study with survival analyses according to the expression of hormonal receptors. METHODS: Total 74 very young women with early breast cancer (invasive ductal carcinoma, NOS, < or=35 years, and stage Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Case-Control Studies ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Medical Records ; Prognosis ; Retrospective Studies ; Survival Rate

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Neoadjuvant Chemotherapy for the Local Advanced Breast Cancer.

Seung Sang KO ; Il Kyoon LEE ; Seung Ki KIM ; Seung Il KIM ; Byeong Woo PARK ; Kyong Sik LEE

Journal of Korean Breast Cancer Society.2002;5(4):311-318. doi:10.4048/jkbcs.2002.5.4.311

PURPOSE: The definition of locally advanced breast cancer (LABC) includes stage III breast cancer. In order to investigate the factors influencing on the final outcome we analysed the data of LABC patients that received neoadjuvant chemotherapy prior to definitive surgery. METHODS: 122 LABC patients, who underwent neoadjuvant chemotherapy between 1980 and 1997, were included for the analysis. Clinical responses to neoadjuvant chemother apy were classified as complete response (CR), partial response (PR), and no response (NR). Overall survival (OS), Loco-regional relapse free survival (LRRFS), and distant relapse free survival (DRRFS) probabilities were investigated according to initial clinical stage, clinical response to neoadjuvant chemotherapy, and pathologic stage after neo adjuvant chemotherapy. Statistical analyses were performed with chi2-test, Kaplan-Meier, and Cox-regression methods using SPSS. RESULTS: The mean age at diagnosis was 47 years old (range 31~73) and median follow-up period was 61.6 months (range 3~227 months). Among 122 LABC patients, 69 (56.6%) were included in stage IIIA, 37 (30.3%) in stage IIIB, and 16 (13.1%) in IIIC at diagnosis. 10 patients (8.2%) have shown CR, 85 (69.7%) patients PR, and the remaining 27 (22.1%) patients showed NR. The overall response rate to neoadjuvant chemotherapy was 77.5%. However, only 51 (41.8%) were demonstrated to have pathologically down-staged results. There were 32 loco-regional recurrences and 59 distant metastases. All of the initial clinical stage, clinical response to neoadjuvant chemotherapy, and pathologic stage influenced the final outcome of 10 year OS, LRRFS, DRFS. However, in multivariate analysis pathologic stage after neoadjuvant chemotherapy was the most influencing factor on the final outcome. CONCLUSION: Pathologic stage after neoadjuvant chemotherapy could be the most important prognostic factor of the LABC.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Diagnosis ; Drug Therapy* ; Follow-Up Studies ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Metastasis ; Recurrence

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Dietary Habit and Cancer Related Information Use in Postoperative Breast Cancer Patients.

Min Hee DO ; Sang Sun LEE ; Pa Jong JUNG

Journal of Korean Breast Cancer Society.2002;5(4):305-310. doi:10.4048/jkbcs.2002.5.4.305

Breast Neoplasms* ; Breast* ; Food Habits* ; Humans

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Detection of Micrometastasis in Peripheral Blood of Breast Cancer Patients Using RT- PCR Assay: Comparison of MUC1, CK19 and hMMG.

Hee Joon KANG ; Sung Hee HONG ; Ho Sung YOON ; Sei Hyun AHN

Journal of Korean Breast Cancer Society.2002;5(4):298-304. doi:10.4048/jkbcs.2002.5.4.298

PURPOSE: Many of breast cancer patients develop distant recurrences after curative surgery. Therefore, tumor cell dissemination must have occurred at the time of disease presentation. We investigated the expression of candidate gene markers: MUC1, cytokeratin 19 (CK19) and mammaglobin (hMMG) in peripheral blood of breast cancer patients to demonstrate prognostic significance of multiple marker RT-PCR assay for detection of micrometastasis in circulation METHODS: RT-PCR assay was used to analyze MUC1, CK19 and hMMG transcripts in peripheral venous blood samples of 47 patients with breast cancer and 14 patients with benign breast disease. Blood samples of 10 healthy volunteers served as negative controls. RESULTS: MUC1 was detectable in all blood samples of patients with breast cancer, benign breast disease and negative controls. CK19 was detectable in blood samples of 31 of 47 patients with breast cancer, 11 of 14 patients with benign breast disease and 10 of 10 negative controls tested positive. While hMMG was detectable in none blood samples with benign breast disease and negative controls, only 3 of 47 breast cancer patients could be detected hMMG expression. CONCLUSION: MUC1, CK19 showed very low specificity and hMMG showed low sensitivity as candidate marker for the detection of micrometastasis. The prognostic significance of RT-PCR assay using these markers could not be demonstrated.
Breast Diseases ; Breast Neoplasms* ; Breast* ; Healthy Volunteers ; Humans ; Keratin-19 ; Neoplasm Micrometastasis* ; Polymerase Chain Reaction* ; Recurrence ; Sensitivity and Specificity

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