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

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

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

PURPOSE: 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. METHODS: We conducted a randomized prospective study to investigate whether concurrent chemotherapy and radiation therapy after breast conserving surgery are associated with increased toxicity. Fifty-seven patients with stage I or II breast cancer were randomly assigned to receive CMF chemotherpy either simultaneously with (n=37) or before (n=20) radiation therapy. RESULTS: Moist desquamation was the most common adverse effect which occurred in 46% (16/37) of the patients treated with concurrent chemotherapy and radiation therapy and 40% (8/20) of those treated with the sequential regimen. This difference between two groups was not statistically significant. Also the incidence of severe neutropenia (WBC<1,800) or abnormal elevation of liver enzymes was not influenced by the sequencing of the adjuvant therapies. Arm edema was observed in 2 patients of the concurrent group and in 2 patients of the sequential regimen. Two patients treated with the concurrent regimen did not complete 6 cycles of chemotherapy while only one patient treated with sequential regimen did not. The incidence of toxicity during chemotherapy was not altered by the timing of radiation therapy. CONCLUSION: Chemotherapy and radiation therapy can be given concurrently after breast conserving surgery in stage I or II breast cancer patients without increase in serious toxicity.
Arm ; Breast Neoplasms* ; Breast* ; Consensus ; Drug Therapy* ; Edema ; Humans ; Incidence ; Liver ; Mastectomy, Segmental ; Neoplasm Metastasis ; Neutropenia ; Prospective Studies ; Radiotherapy*

PURPOSE: It has been reported that the antibody against p53 is detected in a certain proportion of patients with malignancies. The authors designed this study to investigate the correlation between appea rance of the serum p53 antibody and tissue expression of the mutant p53 protein in primary breast carcinomas. METHODS: We conducted assays for the serum p53 antibody in 76 patients with primary breast cancer by using a sandwich enzyme linked immunosorbent assay (ELISA). Immunohistochemical assays for tissue expression of the p53 mutant protein were also undertaken in the same patients, and the results were analyzed according to the patients' outcomes and the clinical/histopathologic parameters. RESULTS: Antibody against p53 was detected as a high titer in the sera of 12 patients (16.9%) whereas the mutant p53 protein was detected in 41.1% of the breast cancer tissues. We found a significant correlation between serum p53 antibody status and tissue expression of the mutant p53 protein (p=0.019), whereas serum p53 antibody status did not correlate with any clinical/histopathologic parameters except the histologic grade of the tumors. The antibody against the p53 protein was more frequently detected in the patients with undifferentiated tumors. In the survival analysis, the serum p53 antibody had no significant correlation with recurrence of the disease or with patient survival. CONCLUSION: It seems likely that accumulation of p53 protein in tumor cells may induce an immune response with the appearance of p53 antibodies in the sera of cancer patients. However, serum p53 antibody status failed to discriminate high risk population of breast cancer patients.
Antibodies ; Breast Neoplasms* ; Breast* ; Enzyme-Linked Immunosorbent Assay ; Humans ; Mutant Proteins ; Prognosis ; Recurrence

PURPOSE: Valid determination of HER2 status is a prerequisite to establish an adequate treatment strategy for breast cancer patients, regardless of the disease stage. The goal of this study was to examine the feasibility of the newly developed silver-enhanced in situ hybridization (SISH) technique as an alternative to fluorescence in situ hybridization (FISH) for HER2 assay in primary invasive breast cancer. METHODS: FISH and SISH for HER2 amplification were performed using tissue microarray. Both methods were used in 257 consecutive primary breast cancers. RESULTS: HER2 amplification was observed in 62 (23.1%) of a total of 257 breast cancers based on SISH. Of the 257 breast cancers measured using both methods, the results of the two methods were consistent in 248 (concordance, 96.5%; kappa=0.903). When we compared HER2 amplification in the primary tumor with the metastatic lymph nodes of the same patients, HER2 amplification was observed in nine cases (14.0%) out of 64 cases in which HER2 was not amplified in the primary tumors. In contrast, HER2 status was completely preserved in metastatic lymph nodes showing HER2 amplification in the primary tumor. CONCLUSION: These results indicate that SISH can be a feasible alternative to FISH in the clinical setting. In node-positive breast cancer, confirmation of the HER2 status of the metastatic lymph nodes appears to be mandatory, regardless of the HER2 status of the primary tumors.
Breast ; Breast Neoplasms ; Fluorescence ; Humans ; In Situ Hybridization ; Lymph Nodes

PURPOSE: The purposes our study was to find out any histologic factors associated with negative conversion of axillary lymph node (ALN) after neoadjuvant chemotherapy (NAC). We also evaluated the association between the decrease in size of primary breast tumor and negative conversion of ALN. METHODS: From January 2012 to November 2014, we included 133 breast cancer patients who underwent NAC and who had ALN metastases which were confirmed on fine-needle aspiration or core needle biopsy at initial diagnosis. All 133 patients underwent initial magnetic resonance imaging (MRI) at the time of diagnosis and preoperative MRI after completion of NAC. We measured the longest dimension of primary breast cancer on MRI. RESULTS: Of 133 patients, 39 patients (29%) showed negative conversion of ALN and of these 39 patients, 25 patients (64%) showed pathologic complete remission of primary breast. On univariate analysis, mean percent decrease in longest dimension, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status and histologic grade were significantly associated with the ALN status after NAC (p<0.001, p=0.001, p< 0.001, p=0.001, p=0.002, respectively). On multivariate logistic regression analysis, percent decrease in longest dimension (odds ratio, 1.026; 95% confidence interval [CI], 1.009-1.044) and histologic grade (odds ratio, 3.964; 95% CI, 1.151-13.657) were identified as being independently associated with the ALN status after NAC. The area under the receiver operating characteristic curve was 0.835 with the best cutoff value of 80% decrease in longest dimension. Combination of high histologic grade and more than 80% decrease in longest dimension showed 64% sensitivity and 92% specificity. CONCLUSION: High histologic grade and more than 80% decrease in primary tumor dimension were associated with negative conversion of ALN after NAC.
Biopsy, Fine-Needle ; Biopsy, Large-Core Needle ; Breast Neoplasms* ; Breast* ; Diagnosis ; Drug Therapy* ; Estrogens ; Humans ; Logistic Models ; Lymph Nodes* ; Magnetic Resonance Imaging ; Neoplasm Metastasis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; ROC Curve ; Sensitivity and Specificity

BACKGROUND: Periampullary cancer is a relatively common malignancy, and its incidence is increasing. Prognosis in these patients depends upon resection of the tumor because surgery is the only effective treatment for irradicating the disease. There has, therefore, been a renewed interest in the role of serological markers early diagnostic tools for periampullary cancer. The potential role of serological markers is not limited only to early detection, but may also be of assistance in the difficult clinical dilemma of differentiating periampullary cancer from other diseases. Furthermore, serological markers of periampullary cancer might be used in follow-up patients after treatment, particularly after surgical resection, in order to select those with minimal disease likely to respond better to adjuvant treatment and/or radiotherapy. METHODS: From March 1989 to May 1997, 54 patients were admitted to Sanggye Paik Hospital, InJe University, and had pathologically confirmed periampullary cancer. Of those, 28 patients underwent a biliary bypass or a drainage procedure [Group I], and the others received resection procedures (Whipple's operation or pylorus-preserving pancreatoduodenectomy)[Group II]. Preoperative and postoperative serum levels of bilirubin, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9(CA19-9) were measured in all patients. We evaluated the relation of the postoperative increase or decrease in those tumor markers to survival, and we discuss the usefulness of those markers as prognostic indicators in periampullary cancer. In this study, we focused on the changes in the CEA and the CA19-9 levels as function of the serum bilirubin concentration change. RESULTS: The bilirubin, CEA, and CA19-9 concentrations decreased significantly in Groups I and II after operation. The correlation between the decreases of the bilirubin and the CEA levels was statistically significant, but that between the bilirubin and CA19-9 had no statistical significance, in spite of the fact that the preoperative and the postoperative tumor marker concentrations had changed markedly. The reason for the statistical insignificance of the CA19-9 result may be the its relatively small sample size and the wide standard variation. The overall median and mean survival time of Group I were 4 months and 11 months, respectively, and those of Group II were 17 months and 21 months. CONCLUSION: We found that the serum the CEA and the CA19-9 levels could be used as a useful prognostic indicator change according to the serum bilirubin concentration even after a biliary drainage procedure and a biliary bypass. We conclude that various biliary bypass and drainage procedures can be effective treatments in periampullary cancer. However, because it is thought that many tumor markers are greatly affected by hyperbilirubinemia, liver dysfunction or cholestasis, further studies of the exact mechanism for the decrease or the increase in the tumor marker level as a function of the serum bilirubin concentration are mandatory. Precise information obtained by using multivariate analysis of large samples is essential for more accurate evaluation.
Biomarkers, Tumor ; Bilirubin* ; Carcinoembryonic Antigen ; Cholestasis ; Drainage* ; Humans ; Hyperbilirubinemia ; Incidence ; Liver Diseases ; Multivariate Analysis ; Pancreaticoduodenectomy* ; Prognosis ; Pylorus* ; Radiotherapy ; Sample Size ; Survival Rate

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*