PURPOSE: Most tests developed for the determination of the HER2 status still require validation, although identification of the HER2 status is important for predicting the response to specific systemic therapy in breast cancer. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed for the HER2 expression on the tissue microarray (TMA) from primary breast cancers to validate the feasibility of IHC for HER2 assay. METHODS: A TMA was constructed from 134~231 primary breast cancers. FISH and IHC were repeated more than twice, and the results were analyzed. Three kinds of primary antibody for IHC were used and compared. RESULTS: The HER2 was amplified by FISH in 24~28% of breast cancer with a concordance between multiple assays of 92~100% (kappa=0.994-0.965), while the HER2 was overexpressed in 21~27% by IHC. The HER2 was amplified in 70~100% of the IHC 3+ cases, but was observed in only 45~78% and 5~12% of the IHC 2+ and IHC 0~1+ cases, respectively. The results from the IHC, using 3 different primary antibodies to HER2, were in good agreement each other at 88~92% (kappa=0.902-0.799). CONCLUSION: The results of the FISH appeared to be more reproducible than those of the IHC in the current study. The results of the IHC were not different from each other according to primary antibody used. However, a considerable proportions of the IHC positive cases were not confirmed by the FISH. This report indicates a need to improve the laboratory quality control measures when using the IHC for the HER2 assay, including the periodic testing for the concordance with FISH.
Antibodies ; Breast Neoplasms* ; Breast* ; Fluorescence* ; Immunohistochemistry* ; In Situ Hybridization* ; Quality Control

PURPOSE: Biologic characteristics of the tumors could be altered after chemotherapy. Accurate assessment of tumor biology before treatment is important for selecting treatment modalities. Current study was designed to investigate whether multiple molecular markers could be accurately assayed on the fine needle aspirates from the breast carcinoma. METHODS: Immunocytochemical assays (ICA) for p53, cyclin D1, and cathepsin D were performed on cytologic samples from 76 primary breast carcinomas, 37 ductal carcinoma in situ (DCIS), and 36 benign ductal hyperplasia. ICA for 3 molecules was also performed on the histologic sections from the matching tumor blocks, and the results were compared. RESULTS: Three molecular markers were successfully detected in cytologic samples from the breast carcinomas; p53 in 71.1% (54/76), cyclin D1 in 73.7% (56/76), and cathepsin D in 44.7% (34/76). Their expression was rarely observed in benign hyperplasia; p53 in 0/36, cyclin D1 in 7/36, and cathepsin D in 4/36. Increase of expression frequency of 3 molecules was apparent through the progress of the disease. Results of ICA for each molecules were well correlated between cytologic and histologic samples; concordance was 93.4% (71/76) for p53, 81.6% (62/76) for cyclin D1, and 73.7% (56/76) for cathepsin D. When 3 molecular markers were integrated to the preoperative diagnosis, positive predictive value was 90.6% for malignant breast disease. CONCLUSION: Three molecular markers were successfully assayed on cytologic samples and well correlated with the results from the histologic sections. The results indicate that the biologic information from the fine needle aspirates can be reliably integrated to patients treatment.
Biology ; Breast Diseases ; Breast Neoplasms* ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Cathepsin D* ; Cathepsins* ; Cyclin D1* ; Cyclins* ; Diagnosis ; Drug Therapy ; Humans ; Hyperplasia ; Needles ; Population Characteristics

Breast conserving surgery is increasingly performed in early stage breast cancer patients. A certain propotion of these patients are at substantial risk for systemic metastasis. However, there is no valid consensus about optimal sequencing of chemotherapy and radiation therapy. We conducted a randomized prospective study to investigate whether concurrent chemotherapy and radiation therapy after breast conservation surgery are associated with increased toxicity. Fifty-seven patients with stage I or II breast cancer were randomly assigned to receive CMF chemotherapy either simultaneously (n=37) or before (n=20) radiation therapy. Moist desquamation was the most common adverse effect which occurred in 46% (16/37) treated with concurrent chemotherapy and radiation therapy while 8 patients (38%) treated with sequential regimen had the finding. Difference between two groups was not statistically significant. Incidence of severe neutropenia (WBC>1,800) or abnormal elevation of liver enzymes was also not influenced by sequencing of adjuvant therapies. Arm edema was observed in 2 patients of concurrent group and was observed in 2 patients treated with sequential regimen. Two patients treated with concurrent regimen did not complete 6 cycles of chemotherapy while one patient with sequential regimen did not complete. Incidence of toxicity during chemotherapy was not altered by timing of radiation therapy. In conclusion, chemotherapy and radiation therapy can be given concurrently after breast conservation surgery in stage I or II breast cancer patients without increase of serious toxicity.
Arm ; Breast Neoplasms* ; Breast* ; Consensus ; Drug Therapy* ; Edema ; Humans ; Incidence ; Liver ; Mastectomy, Segmental ; Neoplasm Metastasis ; Neutropenia ; Prospective Studies

Solid and papillary epithelial neoplasm of the pancreas(SPENP) is an uncommon low grade malignant tumor histologically distinct from the usual ductal adenocarcinoma and amenable to cure by surgical excision. The main features of SPENP are a peculiar morphology, favorable prognosis, and prediction for women 10 and 40 years of age. In men, the occurrence of SPENP seems to be exceedingly rare. The tumor is usually large at the time of presentation, and surgical excision is the treatment of choice. Gross pathologic examination revealed apparent encapsulation, cystic degeneration, and hemorrhagic necrosis. Microscopically, the tumor was characterized by distinctive solid and papillary patterns. This benign or low-grade malignant epithelial tumor is composed of monomorphous cells variably expressing epithelial, mesenchymal, and endocrine markers. The tumor is known to have good prognosis; although local invasion and infiltration of the capsule may occur. Despite growing recognition of this tumor, its histogenesis remains a matter of controversy i.e. pancreatic ductal cell origin, acinar cell origin, pluripotential cell origin. A 44-year-old male presented with an one-year history of postprandial abdominal pain. Following abdominal ultrasonography, computed axial tomography and angiography, a SPENP suspected. The patient underwent exploratory laparotomy. The tumor was located in the head of pancreas. And thus the patient underwent a pylorus-preserving pancreaticoduodenectomy. His postoperative course was uneventful, and he remains well.
Abdominal Pain ; Acinar Cells ; Adenocarcinoma ; Adult* ; Angiography ; Carcinoma ; Female ; Head ; Humans ; Laparotomy ; Male* ; Necrosis ; Neoplasms, Glandular and Epithelial* ; Pancreas* ; Pancreatic Ducts ; Pancreaticoduodenectomy ; Prognosis ; Ultrasonography

PURPOSE: c-myc and HER2 have been reported be amplified in 20% to 30% of clinical breast cancers and appears to be related with poor clinical outcome. The relationship between amplification of c-myc and HER2 and other clinical and biological characteristics of the breast cancers, including clinical outcome, are described. METHODS: c-myc and HER2 amplification were analyzed on 225 consecutive non-selected breast cancers by fluorescence in situ hybridization using tissue microarray technology. RESULTS: c-myc was amplified in 33 cases (15.4%) and HER2 was amplified in 49 cases (23.3%). c-myc amplification was significantly increased with HER2 amplification (p<0.001) and closely linked with cell proliferative activity measured by Ki67 labeling index (p=0.010). In univariate survival analysis, lymph node status, tumor size, and histologic grade of the tumors were significant prognostic factors. However, lymph node status was the only significant prognostic factor for predicting patient survival in multivariate analysis. Patient survival was not different according to c-myc amplification status and c-myc amplification showed no significant correlation with clinco-pathologic parameters of the tumors. CONCLUSION: A strong correlation between c-myc and HER2 amplifications, and cell proliferative activity indicate a biologic link between c-myc and HER2 in breast cancer.
Breast Neoplasms ; Breast* ; Fluorescence ; Humans ; In Situ Hybridization ; Lymph Nodes ; Multivariate Analysis ; Population Characteristics

PURPOSE: The aim of the present study was to evaluate the clinical utility of Ki 67 labelling index and proliferative indices measured by flow cytometry in breast carcinomas. METHODS: We conducted immunohistochemical assay for Ki 67 and analyzed the DNA content and S-phase fraction by flow cytometry in 113 cases of primary breast carcinomas. Relationship between proliferative indices measured by two method and clinical biological parameters was also analyzed. RESULTS: Ki 67 labelling index than average was increased in 53 tumors (46.9%) and demonstrated a significant correlation with S-phase fraction. Higher Ki 67 labelling index was found in 28 (59.6%) of 47 tumors with high S-phase fraction whereas it was found in only 8 tumors (30.8%) with low S-phase fraction. Concordance between Ki 67 labelling index and S-phase fraction was 63.1% (p=0.017). Tumor with high S-phase fraction had a tendency to have an aneuploid. Ki 67 labelling index correlated significantly with histologic grade (p=0.001) and nuclear grade (p=0.001). An inverse correlation was found between Ki 67 and estrogen receptor expression (p=0.004). CONCLUSION: Ki 67 labelling index significantly correlated with S-phase fraction measured by flow cytometry. Ki 67 labelling index seems to be a clinically useful method because it is rapid, practical and easily performed by immunohistchemical assay.
Aneuploidy ; Breast Neoplasms* ; Breast* ; DNA ; Estrogens ; Flow Cytometry*

PURPOSE: We wanted to evaluate the accuracy of sentinel lymph node biopsy (SLNB) in patients with clinically negative lymph node after neoadjuvant chemotherapy. METHODS: Fifty-nine women underwent 4 cycles of neoadjuvant chemotherapy with epirubicin (75 mg/m2) plus docetaxel (75 mg/m2), or with doxorubicin (50 mg/m2), cyclophosphamide (600 mg/m2) and 5-fluorouracil (500 mg/m2) for their primary breast cancer. Their median age was 41 yr (range: 29-62) and all the tumors were larger than 3 cm in maximum diameter. SLNB was performed 3 min after periareolar injection of 1% isosulfan blue dye. All the patients underwent lymph node dissection at the level 1 and 2 axillary areas irrespective of their nodal status. RESULTS: A clinical response after neoadjuvant chemotherapy was observed in 46 patients (88%) and 11 (18.7%) patients had a complete pathologic response. Thirty-five patients (62.7%) underwent breast conserving surgery. The sentinel lymph node was identified in 96.6% and the median number of sentinel nodes was 3 (range: 1-6). The median number of dissected nodes was 14 (range: 11-47). Metastasis to the lymph node was observed in 56% of the patients. The sentinel lymph node was the only metastatic node in 12 patients. Three patients with a negative sentinel lymph node were confirmed to have metastasis to non-sentinel nodes after the final histologic examination (false negative rate: 9.1%). The overall accuracy of SLNB was 94.7%. CONCLUSION: SLNB after neoadjuvant chemotherapy was a safe method in patients with clinically negative lymph node.
Breast Neoplasms ; Cyclophosphamide ; Doxorubicin ; Drug Therapy* ; Epirubicin ; Female ; Fluorouracil ; Humans ; Lymph Node Excision ; Lymph Nodes* ; Mastectomy, Segmental ; Neoplasm Metastasis ; Sentinel Lymph Node Biopsy*

Histologically, the diagnosis of a pure follicular carcinoma of the thyroid is difficult. It is generally not possible to distinguish between a follicular adenoma and a follicular carcinoma without examining the removed specimen, although follicular neoplasms can be identified on cytologic specimens from fine needle aspiration cytology(FNAC). The purpose of the present study is to evaluate the diagnostic accuracy of preoperative FNAC. A total of 42 cases were diagnosed as follicular neoplasms by FNAC while 50 cases were confirmed as follicular tumors after histologic examinations of removed specimens; follicular carcinoma 34, follicular adenoma 10, Hurthle cell carcinoma 3, Hurthle cell adenoma 3. When we compared the postoperative histologic diagnosis of the 42 cases which had been thought to be follicular neoplasms based on FNAC, 31(74.6%) had true follicular tumor; 20 carcinomas, 5 adenomas, and 6 Hurthle cell tumors. The other 11 cases were comprised of 6 follicular variant papillary carcinomas, 4 adenomatous goiters, and 1 instance of Hashimoto's disease. The 34 preoperative diagnoses of follicular carcinomas which were confirmed postoperatively were as follows; follicular neoplasm 20, adenoma 6, papillary carcinoma 5, and Hurthle cell tumor 3. Diagnosis of 10 follicular adenoma was made preoperatively as follicular neoplasm in 5 cases, adenomatous goiter in 3, and Hurthle cell tumor in 2 cases. It was impossible to distinguish a follicular carcinoma from a benign adenoma in 9 cases by using FNAC. Three patients with follicular carcinoma, who underwent a unilateral lobectomy because of inaccurate diagnosis, experienced recurrent disease, 2 with pulmonary metastasis and 1 with bone metastasis, with median follow-up period of 38 months(range: 6~71 months). There are no reliable diagnostic tools to dicriminate between follicular carcinoma and follicular adenoma preoperatively. In conclusion, the best way to establish a diagnosis and to predict prognosis is to surgically remove the tumor for a proper histopathologic examination.
Adenoma ; Adenoma, Oxyphilic ; Biopsy, Fine-Needle* ; Carcinoma, Papillary ; Diagnosis* ; Follow-Up Studies ; Goiter ; Hashimoto Disease ; Humans ; Neoplasm Metastasis ; Prognosis ; Thyroid Gland*

PURPOSE: Breast mass - the most common occurences in the breast must be managed by a method that provides both the best medical and cosmetic results. METHODS: Two hundred seventy-eight patients evaluated and managed for breast mass at our center between January 1998 and December 1999 were analysed. In this study, we compare the results of the triple test score (TTS; sum of physical examination, mammography, and fine needle aspiration cytology) with those from each separate diagnostic test according to a standard formula incorporating sensitivity, specificity, positive predictive value, and negative predictive value. The TTS was modified to substitute sonography for mammography-TTSs. The TTS was also compared to the TTS-2 that double weighted the results of fine needle aspiration (FNA), but was otherwise the same as the TTS. RESULTS: The sensitivity and specificity of breast sonography were 90% and 84% whereas those of mammography were 84% and 73%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of the TTSm (triple test score-mammography) were 99%, 97%, 99% and 97% respectively. The scores of the TTSm-2 were 99%, 100%, 100% and 97%. And those of the TTSs were 100%, 100%, 100% and 100%. CONCLUSION: The TTS was more accurate than each of the elements separately in evaluating breast masses. The TTSs was also more effective than the TTSm. The TTS-2 was more useful than the TTS, being less likely to miss malignancy due to the high accuracy of FNA.
Biopsy, Fine-Needle ; Breast* ; Diagnostic Tests, Routine ; Humans ; Mammography ; Physical Examination ; Sensitivity and Specificity

Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) uptake is known to be increased in breast cancer because of increased blood flow from angiogenesis and heightened metabolism. We performed a 99mTc-MIBI scan in a patient with mammary Paget's disease. The patient had underlying invasive cancer in the same side of the breast. 99mTc-MIBI scan exhibited a scintigraphic image of the uptake from the invasive cancer lesion located deeply in the breast toward the epidermis. 99mTc-MIBI showed an uptake in the deeply located invasive cancer lesion as well as nipple lesion. Especially, the delayed phase of Tc-MIBI scan demonstrated the tumor site more accurately. In conclusion, 99mTc-MIBI scan could be a useful adjunct to clinical decision making in the management of Paget's disease of the breast.
Breast Neoplasms/radionuclide imaging* ; Breast Neoplasms/pathology ; Case Report ; Female ; Human ; Middle Age ; Nipples/pathology ; Paget's Disease, Mammary/radionuclide imaging* ; Paget's Disease, Mammary/pathology ; Skin/pathology ; Technetium Tc 99m Sestamibi/diagnostic use*