A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial) / 한국유방암학회지

Purpose@#Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. @*Methods@#This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.Discussion: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy.We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.

Antiproliferation and Redifferentiation in Thyroid Cancer Cell Lines by Polyphenol Phytochemicals

Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and refractory to radioiodine and thyroid stimulating hormone (TSH) suppression therapy. Redifferentiating agents have been shown to inhibit tumor growth and improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in fruits and vegetables have been reported to inhibit cancer initiation, promotion, progression and induce redifferentiation in selected types. In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These findings suggest that PPs may provide a useful therapeutic intervention in thyroid cancer redifferentiation therapy.

The Author Response: Antiproliferation and Redifferentiation in Thyroid Cancer Cell Line by Polyphenol Phytochemicals

No abstract available.

alphaB-Crystallin is a Novel Oncoprotein Associated with Poor Prognosis in Breast Cancer / 한국유방암학회지

PURPOSE: alphaB-crystallin, a small heat shock protein, is an anti-apoptotic protein associated with aggressive tumor behavior. A recent study revealed that alphaB-crystallin is overexpressed in a metastatic variant of the GI101A human breast carcinoma cell line. The purpose of this study was to investigate whether alphaB-crystallin is related to other breast tumor markers and can predict a breast cancer prognosis. METHODS: Eighty-two patients who underwent breast cancer surgery at Hallym Sacred Heart Hospital were enrolled. alphaB-crystallin expression was determined by immunohistochemical staining. Estrogen receptor, progesterone receptor (PR), human epidermal growth factor receptor, lymphovascular invasion, histological grade, other tumor markers and time to recurrence were compared with alphaB-crystallin expression. RESULTS: alphaB-crystallin expression in breast cancer tissues was associated with PR (p=0.030), the number of metastatic lymph nodes (pN) (p=0.020), lymphovascular invasion (p=0.022), histological grade (p=0.004) and triple negative breast cancer (TNBC) (p=0.004). alphaB-crystallin expression significantly decreased time to recurrence (p=0.039). CONCLUSION: The results revealed a strong relationship between alphaB-crystallin and poor prognostic factors such as the number of metastatic lymph nodes (especially pN2), TNBC, and rapid time to recurrence. We believe that alphaB-crystallin could be a novel oncoprotein biomarker of a poor prognosis in breast cancer.

The Use of a Corrective Procedure with Vicryl Mesh for Oncoplastic Surgery of the Breast / 한국유방암학회지

PURPOSE: In addition to the oncological results, cosmetic results are very important to cancer patients. Currently, the use of oncoplastic surgery is an emerging approach. In this study, we examined the clinical outcomes of the use of a corrective procedure with an absorbable implant, a Vicryl mesh(R), as compared with the use of conventional breast conserving surgery (BCS). METHODS: Fifty six patients who completed questionnaire were enrolled in the study. For 33 cases, BCS was performed concurrently with the use of a Vicryl mesh and for the other 23 cases, conventional BCS alone was performed. Contraindications of the use of corrective procedure were a patient age over 60 year, diabetes, neoadjuvant chemotherapy and a previous excisional biopsy performed on the same breast. Patients rated their cosmetic outcomes by use of a four point scale. RESULTS: For one of 34 cases, the Vicryl mesh was removed due to infection and this patient was excluded from the study. Twenty seven of the remaining 33 patients (82%) who underwent the corrective procedure with Vicryl mesh were satisfied with their outcome. For patients that received conventional BCS only ten of 23 patients (43%) were satisfied with their outcome (p=0.05). Patient age, body mass index (BMI) and tumor location did not affect the cosmetic outcomes of the corrective procedure. When the resection area of the breast was 40-70 cm2, 88% of the patients were satisfied with their outcome. CONCLUSION: This study suggested that the use of Vicryl mesh correction was superior to the use of conventional BCS alone for cosmesis. This method appears to provide a satisfactory outcome for oncoplastic surgery of the breast.

The Number of Removed Lymph Nodes for an Acceptable False Negative Rate in Sentinel Lymph Node Biopsy for Breast Cancer / 한국유방암학회지

PURPOSE: This study was performed to find the adequate number of removed lymph nodes to achieve an acceptable false-negative rate when performing sentinel lymph node biopsy for breast cancer. METHODS: A total of 179 sentinel node biopsies combined with conventional axillary lymph node dissection for breast cancer were performed between November 2003 and June 2007. RESULTS: The overall identification rate of sentinel lymph node and the false negative rate of the biopsy were 95.0% and 8.1%, respectively. Yet the false negative rate of the biopsy was lowered as the number of the removed nodes was increased. Especially, the false negative rate was 0% when more than 4 lymph nodes were removed. CONCLUSION: We recommend that four lymph nodes should be removed to obtain accurate results in sentinel node biopsy for breast cancer.

A Case of Endoscopic Marsupialization of a Nasopalatine Duct Cyst

Nasopalatine duct cysts (NPDC) are common cystic lesions of non- odontogenic origin of the maxilla. Patients with NPDC generally undergo surgical enucleation via transoral approach. However, with the recent introduction of sinonasal endoscopy and subsequent advances in surgical techniques, endoscopic management has become possible. This study reviews a case of a 40- year-old man had a one-month history of nasal obstruction and swelling of the hard palate. Nasal endoscopy revealed a cyst in the nasal floor and hard palate. He underwent successful endoscopic marsupialization of NPDC. This simple and less invasive surgical procedure should be considered in the future treatment of NPDC.

Pathologic Findings of Residual Tumor according to the Response Rate after Neoadjuvant Chemotherapy for Breast Cancer

PURPOSE: There are questions about selecting the best postoperative chemotherapeutic regimen for breast cancer patients who have different response rates after neoadjuvant chemotherapy. The aim of this study was to examine the pathologic findings of residual tumors according to the response rate after neoadjuvant chemotherapy for breast cancer. METHODS: We obtained specimens of residual tumors from 43 breast cancer patients who received neoadjuvant chemotherapy followed by curative operation at the Department of Breast and Endocrine Surgery, Sacred Heart Hospital, between Oct. 2002 and Oct. 2006. Four patients received 3 cycles of FAC (5-FU, Adriamycin, Cyclophosphamide) and 39 patients received 3 cycles of AT (Adriamycin, Docetaxel). We analyzed the pathologic characteristics according to the response rate. RESULTS: The clinical response rate for neoadjuvant chemotherapy was 69.8%. There was no significant difference in the response rate for neoadjuvant chemotherapy between the AT and the FAC regimen groups. The tumors of the complete response group showed to be more ER-negative, PR-positive, p53-negative and c-erb-B2-positive and they had a lower Ki-67 staining index than the tumors of the partial response group. Moreover, the tumors of the clinical complete response group showed more triple (ER/PR/c-erb-B2) negative tumor than did the tumors of the partial response group. CONCLUSION: Although the tumor responded to neoadjuvant chemotherapy, the pathologic findings of the residual tumors in the clinical complete response group differed from that of the partial response group. So, this should be considered for the selection of postoperative chemotherapeutic agents.

The Role of Heat Shock Proteins 70/90 as Potential Molecular Therapeutic Targets in Breast Cancer / 한국유방암학회지

PURPOSE: Heat shock proteins (hsps) are molecular chaperones that are synthesized by cells in response to various stress conditions. The expression of hsps have been shown to be associated with carcinogenesis and the expression of hsps have been implicated in the biological behavior of tumors. Recently, hsps have emerged as novel molecular targets in anticancer protocols. The objectives of this study were to investigate the significance of hsp 70/90 in breast carcinogenesis and effect of geldanamycin (a blocker of hsp 90) and quercetin (a blocker of hsp 70) on growth inhibition in different breast cancer cell lines. METHODS: Breast tissues from 82 patients were obtained between June 2003 and May 2005 at the Department of Surgery, Hallym University Hospital. Expression of hsp 70/90 was studied by immunohistochemistry (IHC) on tissue sections from 63 breast carcinomas and 19 benign breast tissues. Both cytoplasmic and nuclear expression was measured. Expression of hsp 70/90 was also analyzed by use of a Western blot with the breast cancer cell lines. We next investigated the effects of blockers of hsp 70/90 on cell growth of the human breast cancer cell lines. RESULTS: More prominent hsp 90 expression was observed in malignant tissue than in benign tissue by both cytoplasmic and nuclear IHC staining (p<0.001, p<0.001). Nuclear hsp 90 expression was associated with a positive lymph node status (p=0.003) and the presence of poorly differentiated tumors (p=0.028). Expression of hsp 70 was not different in malignant and benign tissues as determined by both cytoplasmic and nuclear IHC staining. The breast cancer cell lines all expressed hsp 70/90. Geldanamycin markedly inhibited the cell growth of these breast cancer cell lines in a dosedependent manner and induced apoptosis in the cell lines. Quercetin inhibited cell growth of the cell lines less efficiently. CONCLUSION: The expression of hsp 90 was associated with breast carcinogenesis and the presence of more aggressive tumors. Geldanamycin inhibited cell growth of hsp 90 expressing breast cancer cell lines. We suggest that Hsp 90 may be a possible molecular target against breast cancer.

Microbiology of Chronic Maxillary Sinusitis in Children / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Problems with antibiotic susceptibility have recently been raised in the treatment of paranasal sinusitis. Therefore, well-established antimicrobial policy is needed. Samples collected in children who have sinusitis can be useful to monitor the evolution of resistance. However, relatively a little is known about the maxillary sinus flora in children with chronic sinusitis. This study aims to get a better insight into the maxillary sinus flora and its resistance. SUBJECTS AND METHOD: Maxillary sinus samples were obtained through inferior meatal puncture from 120 children with history of chronic sinusitis, who have undergone adenoidectomy or adenotonsillectomy. Samples were sent to the laboratory for bacterial cultures and antibiotics sensitivity tests. RESULTS: Organisms were isolated from 142 sinuses (59.0%) of 240 sinus culture, and 98 sinuses (41.0%) were sterile. Among the 142 sinuses, 97 sinuses have single strain, and 45 sinuses have mixed strains. Most recovered organisms were gram (+) aerobes. Among the gram (+) aerobes, Staphylococcus aureus strains in 41 strains (17.1%), -hemolytic Streptococcus in 42 strains (17.5%), coagulase negative Staphylococcusin 15 strains (6.3%) were the commonly encountered organism. In an antibiotic sensitivity test for gram (+) bacteria, Vancomycin and Teicoplanin showed sensitivity over 95%. CONCLUSION: Most isolated organisms were Staphylococcus aureus and -hemolytic Streptococcus. These organisms showed increased resistance to previously used antibiotics, as compared with the result of similar study carried 18 years ago.

Changes of Tumor-infiltrating Lymphocytes in Breast Cancer after Neoadjuvant Chemotherapy

PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study, whether changes in tumor infiltrating lymphocytes take place after neoadjuvant chemotherapy, and if these correlate with the response to treatment in breast cancer were analyzed. METHODS: Neoadjuvant chemotherapy (Adriamycin: 50 mg/m2 +docetaxel: 75 mg/m2, q3wks, 3 treatments) was followed by definitive surgical management. Histological sections from the pre-treatment core-needle biopsy and post-treatment surgical specimens of 17 patients were analyzed for the extent of lymphocytes infiltration. Infiltrated lymphocytes have been recognized as tumor-infiltrating lymphocytes (TILs; lymphocytes present within tumor cell nests). The modified Black's scoring system was used for grading the extent of lymphocytes infiltration, with immunohistochemical (IHC) staining used to characterize the TILs. RESULTS: Pre-treatment lymphocytic infiltrates within the tumor were minimal in the majority of patients, and showed no relationship with the response. A marked increase of TILs after chemotherapeutic treatment was noted in patients according to the following response; complete response: 4/4 (100%), partial response: 2/6 (33.3%), stable disease: 0/7 (0%) (P=0.004). Histological sections stained with IHC staining revealed the increased TILs were CD8 positive cytotoxic T-lymphocytes. CONCLUSION: These results suggest that the development of TILs after treatment correlate with the response to neoadjuvant chemotherapy. Despite the limitation of this preliminary study, the extent of TILs change might be used as a predictor for the therapeutic efficacy of neoadjuvant chemotherapy in breast cancer.

Correlation of Immunohistochemical Expression of MDR1, MRP1, Topoisomerase IIalpha with Prognostic Factors and Histoculture Drug Response Assay (HDRA) Result in Breast Carcinoma / 한국유방암학회지

PURPOSE: Drug resistance plays an important role in the failure of chemotherapy in breast cancer. The purpose of the study was to investigate the chemosensitive and chemoresistance indices of breast carcinomas and see if the in vitro chemosensitivity test correlated with the prognostic indices. METHODS: The immunohistochemical expressions of MDR1, MRP1 and topoisomerase IIalpha(topo IIalpha) were studied and then correlated these with the in vitro chemosensitivities using the histoculture drug response assay (HDRA) and clinicopathological factors in 51 breast carcinomas. RESULTS: In the breast carcinomas examined, the immunohistochemical expressions of MDR1, MRP1 and topo II alpha were strongly observed in 26 (51.0%), 16 (32.0%), 15 (31.3%) carcinomas, respectively. The MRP1 was more frequently expressed in poorly differentiated carcinomas (P= 0.006), and those of MDR1 and topo II alpha were more frequently observed in tumor overexpressing cerbB2 (P=0.038, P=0.036). The expression of MDR1 was related to that of topo II alpha (P=0.015). Comparing these markers with the in vitro chemosensitivities to cyclophosphamide, 5-FU, adriamycin, taxol and taxotere, no correlations were found between the expression of MDR1, MRP1, and topo II alpha but from the chemosensitivity using the HDRA, the growth inhibition rate for cyclophosphamide was higher in MRP1 expressing carcinomas (P=0.009). CONCLUSION: MDR1, MRP1 and topo II alpha were all found to be associated with the poor prognostic indices, but assessment of their immunohistochemical expressions did not allow for prediction of the response to chemotherapy by the in vitro chemosensitivity test in breast carcinomas.

Expression of c-met Gene in Thyroid Tumors

PURPOSE: The hepatocyte growth factor, (HGF)/c-Met, pathway may play various roles in the carcinogenesis of various organs. HGF, a ligand for c-Met, is a pleiotrophic factor that was originally identified as a polypeptide growth factor for hepatocytes. Met protein, known as the HGF receptor, is a transmembrane 190 kDa heterodimer with tyrosine kinase activity, which is encoded by the c-met oncogene. The HGF/ c-Met signalling pathway has been shown to demonstrate various cellular responses including mitogenic, proliferative, morphogenic and angiogenic activities. Although the c-met gene is known to be expressed in a variety of tissues and play important roles in signal transduction, studies of its expression in thyroid tumors are rare. Our objectives were to evaluate the c-met gene expression in benign and malignant thyroid tumors and to correlate this with various clinicopathological facors. METHODS: In this study, the mRNA expression of the c-met was examined by means of a RT-PCR method and the from immunohistochemical expression of c-Met protein in 100 cases of thyroid tumors cases, including 50 papillary carcinomas (pc), 10 follicular carcinomas (fc), and 20 follicular adenomas (fa), 20 nodular hyperplasia (nh). RESULTS: c-met mRNA expression was detected in 10, 20, 40 and 86% of the nh, fa, fc and pc, respectively. Also, c-Met protein expression was detected in 5, 15, 20 and 88% of the nh, fa, fc and pc, respectively. Especially, the c-Met protein expression was higher in well differentiated papillary carcinomas than those that were poorly differentiated, and was statistically significant. Correlation between c-met mRNA and protein expression was recognized in papillary carcinomas. CONCLUSION: These results suggest that the expression of c-met gene expression may be associated with the development of papillary carcinomas of the thyroid. Also, both c-met mRNA and protein expressions may contribute to the morphogenesis of well differentiated papillary carcinomas.

Survival Analysis and Its Prognostic Factors after Distant Relapse in Breast Cancer Patients

PURPOSE: Little attention has been paid to predictive the factors for recurrence and survival after relapse in patients with breast cancer in Korea. The purpose of this study was to identify the survival and potential prognostic factors associated with survival from the time of a distant relapse. METHODS: Between 1989 and 2000, 2355 patients were treated by surgery for breast cancer at the Breast Clinic of the Asan Medical Center. We retrospectively analyzed 247 women who developed a distant relapse among that. RESULTS: The median follow-up duration from the first distant relapse was 10.5 months (0.5-101 months) and the median age at the time of relapse was 46.8 years, retrospectively. The median survival was 19.2 months with a 41.5% and 19.5%, two and five year overall survivals. The dominant sites for the spread were bone (32.0%), lung (29.3%), soft tissue (20.0%) and other visceral organs (18.7%). The median survivals along the site of the relapse were as follows: bone, 26.6; soft tissue, 19.5; lung, 15.8; and other visceral organs, 9.0 months. The location of recurrence, number of metastatic site (both visceral and multiple), the axillary lymph node status (above 4), and operation methods (breast conserving operation) were significantly associated with shorter survivals from the first distant relapse. Conversely, the estrogen receptor status, adjuvant chemotherapy and disease free interval, all failed to reach statistical significance. CONCLUSION: We confirmed that our results for survival of the distant relapsed patients were similar, when comparing to those of Western countries. In this study, the site of the initial recurrence and the axillary lymph node status were important factors for predicting survival after distant recurrence and should help in designing new therapeutic strategies for this group of patients.

Immediate Breast Reconstruction Following Mastectomy for the Treatment of Advanced Breast Cancer Patients

PURPOSE: To elucidate whether there is a delay of adjuvant treatment or detection of recurrences, or an increasing of the recurrence of tumorsin clinically advanced breast cancer patients. METHODS: The study group included 55 patients underwent mastectomy with immediate reconstruction (IBR), and 563 patients who received the mastectomy without reconstruction (non-IBR), and who were stage IIB and IIIA breast cancer patients, at Asan Medical Center between Jun 1993 and December 2000. We retrospectively assessed the comparative outcomes through using follow-up data. RESULTS: Out of 2,057 patients who had undergone the mastectomy on during the period, 175 (8.5%) underwent immediate reconstruction. 55 of them (31.6%) were stage IIB and IIIA patients, a similar portion (29.9%) was seen in the 563 patients of same stages without reconstruction. The mean ages of these groups were 37.1 and 46.9 years, that is, the reconstruction group was about 10 years younger. All these patients voluntarily underwent immediate reconstruction. For the patients who were followed up, the local recurrence was 3.6% (2/55) for the IBR group and 5.2% (29/563) for the non-IBR group. On the other hand, the distant relapse rates were 12.7% and 13.9%. The administration of adjuvant chemotherapy was not delayed and radiotherapy was used as an adjuvant treatment after reconstruction in nine of the cases (16.4%). Chemotherapy was also conducted in 98.2% of the IBR group and 77.3% of the non-IBR group. While radiotherapy was used in the IBR group less frequently, there was no statistical difference between the two groups (P=0.63). CONCLUSION: Immediate reconstruction following mastectomy for the treatment of breast cancer is now more frequently performed. IBR can be done in clinically advanced breast cancer without increasing the risk of treatment failure or modification.

Detection of Axillary Lymph Node Micrometastases in Breast Cancer Using RT-PCR Comparison the Results of MUC1, Cytokeratin 19 / 한국유방암학회지

PURPOSE: The detection of axillary lymph-node micrometastases in breast-cancer patients by using the reverse transcriptase-polymerase chain reaction (RT-PCR) may provide a good guide for postoperative therapy. To evaluate effectiveness of RT-PCR for the detection of micrometastasis, we have compared the results of conventional, immunohistochemical (IHC) staining with those of RT-PCR. Breast cancer, Lymph node micrometastases, MUC1, Cytokeratin 19, RT-PCR ] METHODS: We conducted RT-PCR amplifications of MUC1 and cytokeratin (CK) 19 on lymph nodes from 40 breast- cancer patients and conducted IHC staining for cytokeratin. The results of histological examination and cytokeratin IHC staining were compared with the RT-PCR results for the detection of lymph-node micrometastases. RESULTS: Nineteen of 40 cases (47.5%) were lymph-node positive and twenty-one cases (52.5%) were lymph-node negative. Using RT-PCR MUC1 and CK19 expressions were detected in all positive lymph nodes and in 4 (19.0%) and 5 (23.8%), in negative nodes, respectively. Not all positive nodes were stained by IHC (94.7%), and none of the negative lymph nodes were stained by IHC. Thus, IHC staining was ineffective in detecting micrometastases. CONCLUSION: Detection of MUC1 and CK19 by using RT- PCR can be a more accurate and useful method than IHC staining for the detection of axillary lymph-node micrometastases in breast cancer.

Detection of Breast Cancer Micrometastases in Sentinel Lymph Nodes / 한국유방암학회지

PURPOSE: Axillary lymph node status is a powerful prognostic factor in breast carcinomas. However, patients without axillary lymph node metastases are not completely devoid of risk for relapse. Also, the axillary lymph node micrometastases significantly contribute to the selection of high-risk patients. Recently, sentinel lymph node (SLN) biopsy has been proposed as a potential alternative to full axillary lymph node dissection for staging breast carcinomas. To validate this hypothesis, we evaluated the distribution of occult metastases in sentinel and nonsentinel lymph nodes. METHODS: Twenty patients who had breast carcinomas and who underwent a SLN biopsy followed by an axillary lymph node dissection during March and July 2000 at Seoul National University Hospital were evaluated. Thirty SLNs devoid of metastasis, as determined by hematoxylin and eosin (H&E) staining, were evaluated for micrometastases by pan- cytokeratin immunohistochemistry (IHC) and reverse transcriptase polymerase chain reaction (RT-PCR) using Keratin 19 mRNA and MUC1 mRNA. Nonsentinel lymph nodes (NSLN) were also evaluated by pan-cytokeratin IHC. RESULTS: One out of the 30 SLNs (3.3%) had occult metastases which were identified by IHC and 4 out of the 30 SLNs (13.3%) had occult metastases which were identified by RT-PCR. NSLNs devoid of metastases by H&E staining proved to be free of micrometastases by IHC. CONCLUSION: IHC and RT-PCR are more sensitive methods for detecting micrometastases than conventional H&E stain-ing alone. If an SLN is tumor free by IHC or RT-PCR, we can assume that the remaining lymph nodes in the axilla are also tumor free, consequently, an SLN biopsy can bea substitute for axillary lymph node dissection.

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

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.

Experience of Photodynamic Therapy for Palliation of the Chest Wall and Skin Recurrence in a Patient with Breast Cancer

In patient treated by mastectomy for breast cancer, chest wall and skin recurrences are frequently encountered. Chest wall recurrence results in profound physical and psychological morbidity, and often heralds the appearance of other, more life threatening metastasis. Traditionally the two most common treatments have been site-specific radiation and resection. Photodynamic therapy (PDT) provided an alternative treatment modality using a photosensitizer and laser light to induce selective tumor necrosis. The patient was 64- years old female, had undergone breast conserving surgery for cancer of the right breast. Chest wall and skin metastasis recurred at 40 months after the adjuvant treatment of chemotherapy. The lesions were progressed despite 2nd, 3rd chemotherapy and hyperthermal therapy. The light was administered through a diode laser turned to 630 nm wave length (150 J/cm2 in light dosage, 200 mW/cm2 in intensity), 72 h after photosensitizing agent injection. There was clinical evidence of partial response, defined as granulation tissue with re-epitheliaization from the periphery of normal epithelium. PDT has demonstrated good results in other solid tumors at some hospitals, however there has been no application for breast cancer in Korea previously. Our experience suggests that PDT is non-invasive procedure that is highly tolerable, particularly when compared with other modalities, and an effective treatment method for chest wall or skin recurrence that shows no response to other treatments.

Assessment of MIB1 (Ki-67) Labeling Index and Correlation with Other Well Established Prognostic Factors in Breast Cancer

PURPOSE: The MIB1 labeling index is new method utilizing a monoclonal antibody against Ki-67 antigen and useful for evaluating the proliferation rate in breast cancer due to its ease of use and reliability. We compared the MIB1 labeling index to other, well established prognostic factors and assessed the prognostic value of MIB1 in 564 breast cancers. METHODS: The MIB1 (Ki-67 equivalent monoclonal antibody) proliferation rate, MIB1 labeling index, was determined in formalin-fixed, paraffin-embedded tissue specimens of 564 primary breast cancer patients who underwent surgery between March 1998 and February 2000 at Seoul National University Hospital. The clinicopathologic characteristics of the primary tumor such as age, tumor size, histologic type, nuclear grade, histologic grade, hormone receptor status and various tumor markers (p53, c-erbB-2, bcl-2) were compared with the value of the MIB1 labeling Index. RESULTS: The mean value of MIB1 labeling index was 6.9. MIB1 labeling index was correlated to younger age (p= 0.011), histologic types, low nuclear grade (p=0.0001), high histologic grade (p=0.0001), p53 positive (IDC) (p=0.0001), c-erbB-2 positive (DCIS) (p=0.01), comedo type (DCIS) (p= 0.001) and inversely correlated to hormone receptor positivity (p=0.0001), bcl-2 positive (IDC) (p=0.001). No correlation was found in tumor size, lymph node status and c-erbB-2 positive (IDC). CONCLUSION: The MIB1 labeling index correlated well with well-established poor prognostic factors. The MIB1 labeling index may be an important prognostic determinant in breast cancer.