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: Incidental parathyroidectomy is the most common and unexpected consequence of a total thyroidectomy. It can cause hypocalcemia symptoms such as muscle cramping and even seizures. We conducted this study to compare several factors including the preservation rate of parathyroid glands during both a bilateral axillo-breast approach endoscopic thyroidectomy (BABA) and a conventional open thyroidectomy (CT) for papillary thyroid carcinomas. METHODS: We retrospectively reviewed the medical records of 299 papillary thyroid cancer patients who had a total thyroidectomy between January 2008 and December 2011. We grouped the patients into two groups: BABA (n=70) and CT (n=229). We analyzed age, tumor size, operation time, the number of preserved and removed parathyroid glands, amount and duration of seroma drainage, pain score, hypocalcemia symptoms, and serum total calcium level in both the BABA and CT groups. RESULTS: We observed a younger age (under 45 years old) (P=0.000), smaller tumor size (P=0.000), longer operation time (P=0.000), larger amount of drainage (P=0.000), longer duration of drainage (P=0.007), and larger pain score (P=0.000) in the BABA group. Of the 70 patients that received an endoscopic thyroidectomy, we preserved all four parathyroid glands in 56 patients (78.6%). Of the 229 patients that received an open thyroidectomy, we preserved all four parathyroid glands in 141 patients (61.6%, P=0.004). CONCLUSION: BABA results in more extensive tissue damage over a longer period of time than CT. However, BABA was an excellent method for preserving parathyroid glands when compared with CT for thyroid carcinoma. Thus, it seems to be feasible performing BABA when it matches the indications.
Calcium ; Drainage ; Humans ; Hypocalcemia ; Hypoparathyroidism ; Medical Records ; Methods ; Muscle Cramp ; Parathyroid Glands* ; Parathyroidectomy ; Retrospective Studies ; Seizures ; Seroma ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy*

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: 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 optimal sequence of chemotherapy (CT) and radiotherapy (RT) remains uncertain although both can reduce breast cancer recurrence after breast-conserving surgery (BCS). The current study was performed to evaluate whether concurrent RT with CT increases chemotherapy-associated toxicities. METHODS: Two hundred and thirty-eight patients with stage I and II breast cancers were prospectively allocated concurrent CT and RT (N=133) or sequential CT and RT (N= 105) after BCS. In the sequential group, the RT was started after completion of 3 cycles of CT with an additional 3 cycles of CT delivered after the RT. All patients underwent intravenous CMF chemotherapy composed of cyclophosphamide (500 mg/m2), methotrexate (50 mg/m2) and 5-FU (500 mg/ m2), every 3 weeks for 6 cycles following surgery. RESULTS: There were no significant differences between the two groups with regard to the grade 3 or 4 hematologic toxicities during chemotherapy or in abnormal liver enzyme elevation. Radiation related adverse effects, such as moist desquamation and pneumonitis symptom, were no different between the two groups. During the median 42 month follow-up period, range 16- to 60 months, 18 (13.5%) and 20 (19.1%) patients in the concurrent and sequential groups had systemic recurrences of breast cancer. The disease-free survival and local recurrence rates were no different between the two groups. CONCLUSION: Concurrent CT and RT were not associated with an increased toxicity and reasonable cosmetic results were achieved in this current study. The current study indicates that concurrent RT with CT after BCS is a feasible treatment modality, with the advantage of a shortening treatment time.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant* ; Cyclophosphamide ; Disease-Free Survival ; Drug Therapy ; Fluorouracil ; Follow-Up Studies ; Humans ; Liver ; Mastectomy, Segmental* ; Methotrexate ; Pneumonia ; Prospective Studies ; Radiotherapy* ; Recurrence

A 59-year-old woman displayed multiple palpable right breast masses along with ipsilateral cervical and axillary lymphadenopathy. She had a previous history of bilateral salpingo-oopho- rectomy for serous papillary adenocarcinoma two and half years ago. She underwent mastectomy for the lesions located in the upper inner breast quadrant. A 1 cm-sized primary ductal carcinoma was present; however, the other breast lesions and the metastatic axillary lymph nodes were confirmed as showing papillary serous adenocarcinoma, which were similar to the previous ovarian tumor. After the patient underwent postoperative adjuvant chemotherapy, of 8 cycles of doxorubicin and docetaxel, she has been stable during the clinical follow-up for 10 months with decreases in size of the metastatic nodules.
Adenocarcinoma ; Adenocarcinoma, Papillary* ; Breast* ; Carcinoma, Ductal* ; Carcinoma, Ductal, Breast ; Chemotherapy, Adjuvant ; Doxorubicin ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; Lymphatic Diseases ; Mastectomy ; Middle Aged ; Neoplasms, Multiple Primary ; Ovarian Neoplasms