Clinicopathologic Significance of BRAF Mutation and Extracellular Signal Regulated Kinase 1/2 Expression in Patients With a Colorectal Adenocarcinoma

PURPOSE: BRAF mutation and expression of extracellular signal regulated kinase (ERK) are linked with colorectal carcinogenesis through the serrated pathway. BRAF and ERK1/2 play important roles in the activation of mitogen-activated protein (MAP) kinase signaling pathways. The present study investigated the clinicopathologic outcomes of BRAF mutation and ERK1/2 expression in patients with colorectal cancer (CRC) and the possibility of using them as prognostic indicators. METHODS: Dual-priming oligonucleotide-based multiplex polymerase chain reaction for BRAF(V600E) mutation and immunohistochemical analysis of ERK1/2 were performed using 65 formalin-fixed, paraffin-embedded samples from patients with CRC. We analyzed the dependences of the clinicopathologic features on BRAF mutation and ERK1/2 expression. RESULTS: Out of 65 samples from CRC patients, BRAF mutation was detected in 3 (4.6%). The 3 patients with BRAF mutation presented with T3 CRC with lymph node metastasis (stage III) showing moderately or poorly differentiated histology. ERK1 and ERK2 were positively detected in 73.8% and 15.4% of the patients with CRC, respectively. ERK1 expression was significantly correlated with lymph node metastasis (P = 0.049). ERK2 expression was significantly correlated with tumor emboli (P < 0.05), tumor invasion (P = 0.035), lymph node metastasis (P = 0.017), and stage (P = 0.02). CONCLUSION: BRAF mutation and ERK1/2 expression may be associated with advanced or more aggressive CRC. These molecular markers might play prognostic roles in CRC developed through the serrated pathway.

Occurrence of colonic liposarcoma after retroperitoneal liposarcoma

No abstract available.

Double Intussusceptions with Necrotizing Enterocolitis Diagnosed in a Premature Infant

Intussusception in neonates, especially in preterm infants, is rare. Common symptoms of intussusception, which include distended abdomen and gastric residuals, lead to misdiagnosis as necrotizing enterocolitis (NEC). Delayed diagnosis of neonatal intussusception delays treatment as well, which can lead to life-threatening complications. The predominant location of intussusception in preterm neonates is the small bowel; therefore, ultrasonography is not indicated. We report the case of an 834g male baby born at 25 weeks 6 days of gestation, who was diagnosed with double intussusceptions with NEC.

Single port laparoscopic appendectomy in children using glove port and conventional rigid instruments

PURPOSE: To further improve the advantages of minimally invasive surgery, single port laparoscopic techniques continue to be developed. We report our initial experience with single port laparoscopic appendectomy (SPLA) in children and compare its outcomes to those of conventional laparoscopic appendectomy (CLA). METHODS: Clinical data were prospectively collected for SPLA cases performed at Chung-Ang University Hospital by a single surgeon between March 2011 and December 2011, including operative time, perioperative complications, conversion rate, and length of hospital stay. Each case of SPLA was performed using conventional laparoscopic instruments through Glove port placed into the single umbilical incision. To compare outcomes, a retrospective review was performed for those patients who underwent CLA between March 2010 and December 2010. RESULTS: Thirty-one patients underwent SPLA and 114 patients underwent CLA. Mean age (10.5 years vs. 11.1 years, P = 0.43), weight (48.2 kg vs. 42.9 kg, P = 0.27), and operation time (41.8 minutes vs. 37.9 minutes, P = 0.190) were comparable between both groups. Mean hospital stay was longer for CLA group (2.6 days vs. 3.7 days, P = 0.013). There was no conversion to conventional laparoscopic surgery in SPLA group. In CLA group, there were nine complications (7.9%) with 3 cases of postoperative ileuses and 6 cases wound problems. There was one complication (3.2%) of umbilical surgical site infection in SPLA group (P = 0.325). CONCLUSION: The results of this study demonstrated that SPLA using conventional laparoscopic instruments is technically feasible and safe in children. SPLA using conventional laparoscopic instruments might be popularized by eliminating the need for specially designed instruments.

Case of Small Bowel Perforation due to Enteropathy-Type T-Cell Lymphoma

Enteropathy-type T-cell lymphoma (ETTL) is a rare disease with a poor prognosis. According to the World Health Organization (WHO) classification, it is a subtype of the peripheral T-cell lymphomas. This disease is associated with gluten-sensitive enteropathy, has a high risk of intestinal perforation and obstruction, and is refractory to chemotherapeutic treatment. We report the case of a 73-year-old woman who was diagnosed with enteropathy-type T-cell lymphoma of the small intestine, which was positive for the markers of cytotoxic T cells, CD3, CD8, and CD56, on immunohistochemical staining after resection of the perforated terminal ileum.

Expression of Proteins Related Cell Cycle and Apoptosis during Diethylnitrosamine (DEN)-induced Hepatocarcinogenesis in Rats

PURPOSE: To explore the role of cell cycle and apoptosis regulators during hepatocarcinogenesis, the expression of cell cycle-related proteins (cyclin D1 and p27kip1) and apoptosis-related proteins (p53, survivin, caspase 3). METHODS: Sprague-Dawley rats were given 120 ppm diethylnitrosamine (DEN) as a carcinogen and sequentially sacrificed. The expression of cell cycle and apoptotic related proteins were examined by light microscopy and immunohistochemistry. RESULTS: During the DEN-induced hepatocarcinogenesis, sequential histologic changes from preneoplastic lesions (altered hepatic cellular foci, hyperplastic nodules, and hepatocellular adenomas) and ultimately overt hepatocellular carcinomas and metastatic lesions were noted. The cyclin D1 were progressively increased from preneoplastic lesions to hepatocellular carcinomas. However, the p27kip1 and the survivine proteins did not show any other difference with the increasing degree of carcinogenesis. The p53 and caspase 3 proteins were more significantly increased in hepatocellular carcinomas than preneoplastic lesions. The cyclin D1 protein expression did not show any correlation with the expression of p27Kip1 protein, but the p53 expression was related to the expression of survivin and caspase 3. CONCLUSION: From the above results, over-expression of cyclin D1 plays a role in the early and late stages of hepatocarcinogenesis. In addition p53 and caspase 3 might be useful markers for evaluating the risk of malignant transformation.

Significance of Intra & Extra Hepatic Duct Stone Removal via Percutaneous Transhepatic Biliary Drainage Tube in Patients Undergoing Laparoscopic Cholecystectomy

PURPOSE: One of the popular and widespread treatments for intra- & extra-hepatic duct (IEHD) stone associated gallbladder (GB) stone is laparoscopic cholecystectomy (LC) with stone removal through endoscopic retrograde cholangiopancreatography (below ERCP). Because LC with stone removal through percutaneous transhepatic biliary drainage (below PTBD) is well known for its safety and feasibility in removing IEHD stones, we did this study to see the significance (safety, feasibility, effectiveness etc) of PTBD and stone removal. METHODS: We compared the odds by collecting 71 retrospective cases, victims of IEHD stone associated GB stone from January, 2004 to December, 2007 in Chung-Ang University Hospital. Comparative analysis took place in 51 cases who underwent PTBD and 20 cases treated with ERCP. We excluded 6 patients who underwent PTBD for intra hepatic duct stone. Age, sex, American Society of Anesthesiologists score, pain, nausea, pre- and post- laboratory value, symptoms, size, location and number of stones, diameter of extra hepatic duct, recurrence and clearance rate, frequency of each procedure, complications, cost were investigated in this study. RESULTS: There were no statistical differences in each group in recurrence and clearance rate or frequency of procedure. However post-procedure pancreatitis and amylase level were significantly difference in each group. PTBD group experienced much longer hospital stay but was not significantly different. Although procedure cost is three times more expensive than that of PTBD group, there were no differences in total cost and patients' expenses between the two groups. CONCLUSION: PTBD would be an alternative solution in managing IEHD stone associated with GB stone for its lower rate of complication, higher clearance with minimal discomfort.

The Immunohistochemical Expression of Nuclear Retinoid Receptor and CREB in Gastric Adenocarcinoma

PURPOSE: Transcriptional factors of CREB (cAMP response element binding protein) are involved in regulating the gene expression in response to a variety of signaling pathways. The proteins produced by the CREB genes play key roles in many physiological processes, including memory and long-term potentiation. The retinoic acid receptor (RAR) axis mediates epithelial cell differentiation and proliferation in many tissues. This study examined the expressions of RAR and CREB and their relationship with the clinicopathologic factors and their significance. MATERIALS AND METHODS: The levels of the RAR and CREB expressions were measured in 150 gastric adenocarcinomas by performing immunohistochemical staining. RESULTS: 1. An RAR protein expression was found in 63.3% of the adenocarcinomas (95/150) and a CREB expression was found in 60.7% (91/150) of the adenocarcinomas. 2. An RAR protein expression was found in 72.2% (78/108) of the intestinal type adenocarcinomas and in 40.5% (17/42) of the diffuse type adenocarcinomas (P0.05). Based on the depth of invasion, a CREB expression was found in 50% (12/24) of the T1 adenocarcinomas, in 52.4% (11/21) of the T2 adenocarcinomas, in 64.6% (62/96) of the T3 adenocarcinomas, in 66.6% (6/9) of the T4 adenocarcinomas, in 71.1% (59/83) of the adenocarcinomas with lymph node metastasis and in 47.8% (32/67) of the adenocarcinomas without lymph node metastasis (P<0.01). 4. The RAR protein and CREB expressions coincided in 71.4% of the gastric adenocarcinomas, and a significant correlation between them was found (P<0.05). CONCLUSION: We found a significant relationship between the expression of RAR and CREB and the histology and lymph node metastasis of gastric cancer. Further studies are needed to confirm their biologic meaning in gastric carcinogenesis.

Immunohistochemical Study of the C-erbB-2, COX-2, MMP-9, p53 and VEGF Expressions in Hepatobiliary and Pancreatic Adenocarcinoma

PURPOSE: Researching the inhibitors of the gene products that participate in the multistep carcinogenetic events of human cancer is important for chemoprevention or adjuvant cancer therapy. This study was performed to search for basic data for the chemoprevention or adjuvant therapy of human hepatobiliary and pancreatic adenocarcinoma, and we wanted to evaluate the coexpression of each gene product and the relationship between the expression of each gene product and the clinocopathologic factors and the prognosis. METHODS: The following formalin-fixed paraffin embedded surgical specimens were immunohistochemically stained by the avidin-biotin complex method for C-erbB-2, COX-2, MMP-9, p53 and VEGF. There were 15 cases of intrahepatic cholangiocarcinoma, 12 cases of metastatic adenocarcinoma in the liver, 15 cases of gallbladder adenocarcinoma, 25 cases of extrahepatic bile duct adnocarcinoma involving the ampullary region and 20 cases of pancreatic ductal adenocarcinoma. RESULTS: Varying frequencies of the overexpressions of the five gene products in the hepatobiliary and pancreatic adenocarcinomas were noted. Although the coexpression of the five gene products was observed to various degrees, the VEGF expression was statistically correlated with the expressions of COX-2 (in the intrahepatic cholangiocarcinoma) MMP-9 (in the glalbladder adenocarcinoma) and p53 (in the extrahepatic bile duct and pancreatic duct adenocarcinoma) (P<0.05). There was also statistical correlation between the C-erbB-2 and COX-2 expressions and the clinical stage of adenocarcinoma of the extrahepatic bile ducts (P<0.05). CONCLUSION: These results suggest that the overexpression of the five gene products was one of the important multistep carcinogenetic events, and the VEGF expression might play an important role in the coexpression of other gene products of hepatobiliary and pancreatic adenocarcinoma.

Adrenal Ganglioneuroma Treated by Laparoscopic Surgery

Adrenal ganglioneuromas are rare benign tumors arising from the neural crest tissue of the sympathoadrenal nervous system. Because most of these tumors are hormonally silent and patients with them are often asymptomatic, they are often identified incidentally in patients undergoing abdominal imaging studies for unrelated reasons. Diagnosis of this entity is very difficult to make, with definitive diagnosis being based on histological examination. Surgical resection may be both diagnostic and therapeutic. A technique for laparoscopic adrenalectomy of benign adrenal tumors has recently been developed. If the tumor is excised with an adequate resection margin, the postoperative prognosis is very good. In this report, we describe two cases of adrenal ganglioneuroma that were treated using a laparoscopic resection procedure, and we also present a review of the pertinent literature.

Angiogenic and Lymphangiogenic Microvessel Density in Terms of the Expression of CD31 and D2-40 in Colon Cancer

PURPOSE: Angiogenesis and lymphangiogenesis play important roles in the growth, progression and metastasis of colon cancer. We performed this study in order to investigate the significance of the CD31 and D2-40 expressions as prognostic factors in colon cancer. METHODS: The angiogenic and lymphagiogenic microvessel density was assessed by immunohistochemical staining of CD31 and D2-40 on samples that were resected from 66 patients with colorectal cancer. RESULTS: Strong correlation was observed between the CD31 microvessel density and being positive for having tumor emboli and lymph node metastasis (P=0.001, P=0.003). The D2-40 lymphatic vessel density was correlated with being positive for having tumor emboli (P=0.0001), the depth of invasion (P=0.0001), lymph node metastasis (P= 0.0001) and the cancer stage (P=0.0001). The D2-40 lymphatic vessel density was also correlated with the CD31 count (P=0.003). CONCLUSION: These results suggested that the CD31 and D2-40 expressions are useful predictors of lymph node metastasis and they are prognostic factors for colon cancer.

Significance of the Decreased Expressions of Claudin-1 and ZO-1 Protein as Prognostic Factors in Breast Cancer

PURPOSE: Tight junction proteins are either over-expressed or suppressed in some cancers. These suppressions of claudin-1 and ZO-1 protein are known to have a significant relationship with the progression of breast cancer. The authors reviewed 42 cases of breast cancer and the staining status of claudin-1 and ZO-1 in order to evaluate Claudin-1 and ZO-1 as clinicopathologic risk factors. METHODS: Immunohistological staining for Claudin-1 and ZO-1 was performed in 42 post-operative pathologically diagnosed infiltrating duct carcinoma specimens. The rate of expression was compared with the clinical record, the pathological diagnosis, the estrogen receptor and progesteron receptor status and the c-erbB2 gene to evaluate the protein expression-breast cancer progression relationship and to investigate the expressions of Claudin-1 and ZO-1 as a prognostic factors in breast cancer. RESULTS: The claudin-1 and ZO-1 expressions were both decreased in all the post-operative specimens. The claudin-1 expressions were significantly decreased 100%, 82.4% and 66.7% as the histologic grade increased. The ZO-1 expressions were shown in 44.8% of the lymph node metastasis negative group and in 7.7% of the lymph node positive group. The expression of ZO-1 decreased by 53.3%, 28.6% and 0%, with statistical significance, as the stage increased. CONCLUSION: The claudin-1 expressions were decreased in the poorly differentiated group, i.e., a high histologic grade, and the ZO-1 expressions were decreased in the lymph node positive group and in the high stage cancer. This shows the possibility of Claudin-1 and ZO-1 as factors for tumorigenesis and progression and as prognostic factors in breast cancer.

Amplification of the HER-2/neu Oncogene and Topoisomerase II-alpha by Chromogenic in Situ Hybridization in Breast Cancer

PURPOSE: HER-2/neu is the most frequently amplified oncogene in breast cancer. Topoisomerase II-alpha is a key enzyme in DNA replication and it is a molecular target for many anti-cancer drugs that are called topo II inhibitors; in addition, it is a new marker of proliferation. Because of the physical proximity of the ER-2/neu and topoisomerase II-alpha genes, co-amplification of the HER-2/neu and topoisomerase II-alpha may be important determinates of the response to chemotherapy for advanced breast cancer patients. METHODS: We studied the correlation of gene amplification of HER-2/neu and topoisomerase II-alpha by chromogenic in situ hybridization (CISH) in 43 infiltrating duct carcinomas of the breast. The over-expression of HER-2/neu protein and the staining index for the proliferation marker of topoisomerase II-alpha were examined immunohistochemically. The correlations between the status of HER-2/neu and topoisomerase II-alpha and the other clinicopathologic variables such as tumor size, lymph node metastasis, TNM stage, histologic grade, nuclear grade, and the estrogen receptor and progesteron receptor were investigated. RESULTS: Of the 43 infiltrating ductal carcinomas, the amplifications of HER-2/neu and topoisomerase II-alpha by CISH were observed in 8 cases (18.6%) and 14 cases (32.6%), respectively. Amplification of HER-2/neu showed the statistically significant correlations with tumor size, histologic grade and the topoisomerase II-alpha staining index. Amplification of topoisomerase II-alpha showed statistically significant correlations with axillary lymph node metastasis, the stage, the nuclear grade and the estrogen receptor status. CONCLUSION: These data suggest that amplification of HER-2/neu oncogene and topoisomerase II-alpha by CISH may be valuable for determining the response to chemotherapy, and detection of HER-2/neu and topoisomerase II-alpha in tumor sections may have prognostic value in human breast cancer.

Expression of Panendothelial and Lymphatic Vessel Markers of a Pre-operative Biopsy Specimen from Colorectal Cancer

PURPOSE: Panendothelial markers such as factor VIII, CD34, CD31, CD105 (endoglin) and D2-40 are useful to identify proliferating endothelium that is related to tumor invasion. This study was designed to identify the correlation between the expressions of panendothelial and lymphatic vessel markers in preoperative biopsy specimens and the clinicopathologic factors. METHODS: Preoperative biopsy specimens from 72 patients were immunostained for CD105, CD34, CD31, Factor VIII and D2-40. The microvessel and lympathic vessel densities (MVD and LVD) were counted in dense vascular foci (hot spots) on a x200 field in each specimen. The correlation between these factors and the clinicopathologic parameters were analyzed. RESULTS: The MVD by CD105 showed statistically significant correlation with tumor emboli, the T-stage, nodal metastasis and the stage, and the MVD by CD34 had statistically significant correlation with tumor emboli, nodal metastasis and the stage. The lympathic vessel density (LVD) by D2-40 showed a statistically significant correlation with tumor emboli, the T-stage and nodal metastasis. CONCLUSION: The MVD by CD105 and the LVD by D2-40 in preoperative biopsy specimens of colorectal cancers may be useful markers for the prediction of invasiveness.

Changes of Plasma and Liver Tissue Levels of VEGF, bFGF and Endostatin in the N, N- Diethylnitrosamine-induced Hepatocarcinogenesis and Progression in Rat Liver

PURPOSE: Proangiogenic and antiangiogenic growth factors are related to control of cancer progression and metastasis. The expression of Factor VIII-Related antigen in liver, that is marker of the vascular endothelial cell antigen, may be an indicator of neovascularization. This study aimed to monitor the change of plasma and tissue levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and endostatin in rat liver carcinogenesis and to determine the possibility of the future predictive indicator and antiangiogenic therapy application. METHODS: Sprague-Dawley Rats received 120 ppm concentration diethylnitrosamine (DEN) in drinking water as a carcinogen and in control and experimental groups, sequentially sacrificed by three and seven rats at 3, 6, 9, 12, 15 and 18 weeks, respectively. The liver tissue was examined with light microscopy, immunohistochemistry and enzyme immunoassay method. RESULTS: In hepatocarcinogenesis, the preneoplastic nodules appeared at 6 weeks after oral 120 ppm concentration DEN administration. The hepatocellular carcinomas and their pulmonary metastatic foci developed at 15 weeks and 18 weeks, respectively. The immunohistochemical staining of Factor VIII-Related antigen was negative in all sinusoids in normal control livers, but focal or scattered expression in preneoplastic nodules and diffuse expression were found in hepatocellular carcinomas. The tissue levels of VEGF and bFGF were found to have a direct correlation with the plasma levels, but not endostatin. The levels of VEGF and bFGF increased slightly in preneoplastic nodules and markedly elevated in hepatocellular carcinoma. However, there was no significant difference between the levels of VEGF and bFGF and the state of metastasis. There was no significant relation between the levels of endostatin and carcinogenesis and progression of the rat liver. CONCLUSION: From the above results, it could be suggested that VEGF and bFGF may play an important role in initiation and progression of hepatocellular carcinomas in rat liver, but not endostatin. Also, there was no correlation between the levels of VEGF and bFGF and the state of metastasis. Therefore, further study to determine the relationship between the angiogenic regulators and its receptors will serve as a promising research in the predictive indicator and antiangiogenic therapy.

Expression of Thyroid Transcription Factor-1 and Ki-67 in the Thyroid Neoplasms

PURPOSE: Thyroid transcription factor-1 (TTF-1) has been known to regulate the transcriptional activity of thyroid-specific genes. Ki-67 has been known as a marker for indicating tumor growth. This study was designed to campare the expressions of TTF-1 and Ki-67 on non- neoplastic and neoplastic thyroid tissues. METHODS: The surgically resected specimens of various histological types of thyroid tumor, from the files of the Dept. of surgery, Chung-Ang University Pil-Dong Hospital, between January 1998 and June 2002 were reviewed, and 55 cases selected for immunohistochemical studies. The materials consisted of tissues from 10 nodular hyperplasias, 28 papillary carcinomas, 15 follicular adenomas and 12 follicular carcinomas. All specimens were routinely processed, and paraffin blocks were available in all cases. Immunohistochemical stains for TTF-1 and Ki-67 were also performed. RESULTS: In all the cases, including the nodular hyperplasias, papillary carcinomas, follicular adenomas and follicular carcinomas, expressions of the TTF-1 were observed. The properties of the TTF-1 expression, including staining intensity, extent and index were not related to the tumor type. The expression of TTF-1 was inversely correlated with the tumor proliferation fraction, as assessed by the Ki-67 staining index. CONCLUSION: TTF-1 was expressed in almost all the benign lesions and well differentiated carcinomas, and correlated with the tumor proliferation fraction.

Clinical Analysis of Primary Hyperparathyroidism / 대한내분비외과학회지

The authors present a clinical analysis of 69 cases of primary hyperparathyroidism during the last 32 years from 1963 to 1994 which were reported in Korean Medical Journals. There were 69 patients, 21 males and 48 females, with a male to female ratio of 1 to 2.3. The age distribution was between 4 months and 65 years. The presenting clinical manifestations were musculoskeletal symptoms (66.7%), renal symptoms (49.3%), and general weakness (21.7%) in that order of frequency. There were 2 patients with asymptomatic hypercalcemia. The mean preoperative serum Ca and P levels were 13.1 mg% and 2.4 mg%. The mean postoperative serum Ca and P levels were 8.0 mg% and 2.7 mg%. The mean preoperative and postoperative PTH levels were 3275 pg/dl (normal range; 220~660 pg/dl) and 392 pg/dl. Preoperative localization was done using ultrasonogram, computed tomogram, thallium-technetium subtraction scan, and arteriogram. Positive localization was made in 84.8% (28/33), 72.7% (24/33), 84.2% (16/19), and 100% (9/9), respectively. In one patient, magnatic resonance imaging was performed and positive localization was made. The location of the lesion was more common in the lower part of thyroid than the upper part and on the left side rather than the right side. There were 7 patients with ectopic locations including the thoracic inlet (2), intrathymus (1), intrathyroidal (1), mediastinum (2), and right subclavicular (1). All patients were treated surgically. The final histopathologic findings were single adenoma in 63, carcinoma in 3, and primary hyperplasia in 2 patients. There was 1 patient with double tumors composed of adenoma and carcinoma.

A Case of Femoral Neuropathy after Renal Transplantation / 대한이식학회지

A few cases of femoral neuropathy that were developed after renal transplantation have been reported in western literature. The possible causes of this neuropahty that discussed in recent studies are compression of nerve by self-retaining retractor during operation, ischemia of femoral nerve by iliac muscle hematoma etc. We experienced one case of femoral nerve neuropathy after right iliac fossa renal transplantation that developed at first postoperative day without definitive etiology in all study. It was improved symptomatically after 2 weeks of postoperative day, so we reported this case with brief review of the literatures.

Expression of Topoisomerase II-alpha and c-erbB-2 in Breast Cancer / 한국유방암학회지

PURPOSE: Topoisomerase II-alpha is a key enzyme in DNA replication and a molecular target for many anti-cancer drugs. The C-erbB-2 oncogene (HER-2/neu) is the most frequently amplified oncogene in breast cancer. Because of the physical proximity of c-erbB-2 and topoisomerase II-alpha, co-amplification of the c-erbB-2 and topoisomerase II-alpha may occur. To investigate the clinical significance of the topoisomerase II-alpha and c-erbB-2, the correlation between topoisomerase II-alpha and c-erbB-2 was examined by immunohistochemical staining in 43 invasive ductal breast carcinomas and its relationship with other prognostic factors. METHODS: Topoisomerase II-alpha and c-erbB-2 expression was studied immunohistochemically using sections of formalin fixed, paraffin-embedded tumor specimens from 43 invasive ductal breast carcinomas. The correlation between topoisomerase II-alpha and c-erbB-2 expression, and its relationship with the clinicopathological factors such as the tumor size, lymph node metastasis, TNM stage, histological grade, nuclear grade, estrogen receptors and progesteron receptors was investigated. RESULTS: C-erbB-2 was expressed in 9 (20.9%) out of the 43 infiltrating ductal carcinoma cases. Among the prognostic factors, the tumor size, lymph node metastasis, tumor stage, nuclear grade, status of progesteron receptors and estrogen receptors did not significantly correlated with c-erbB-2 expression. The tumor size, lymph node metastasis, tumor stage, histological grade, and the absence of estrogen receptors displayed a significant relationship with the increase in the topoisomerase-alpha index. However, the topoisomerase II-alpha index did not correlate with the nuclear grade and the status of progesterone receptors. The topoisomerase II-alpha index was slightly higher in the c-erbB-2 positive expression cases compared to c-erbB-2 negative expression cases but this increase was not significant (P=0.503). CONCLUSION: These results suggest that topoisomerase II-alpha may play some role as a prognostic factor, but further investigation is needed.

Expression of Topoisomerase II-alpha and c-erbB-2 in Breast Cancer

PURPOSE: Topoisomerase II-alpha is a key enzyme in DNA replication and a molecular target for many anti-cancer drugs. The C-erbB-2 oncogene (HER-2/neu) is the most frequently amplified oncogene in breast cancer. Because of the physical proximity of c-erbB-2 and topoisomerase II-alpha, co-amplification of the c-erbB-2 and topoisomerase II-alpha may occur. To investigate the clinical significance of the topoisomerase II-alpha and c-erbB-2, the correlation between topoisomerase II-alpha and c-erbB-2 was examined by immunohistochemical staining in 43 invasive ductal breast carcinomas and its relationship with other prognostic factors. METHODS: Topoisomerase II-alpha and c-erbB-2 expression was studied immunohistochemically using sections of formalin fixed, paraffin-embedded tumor specimens from 43 invasive ductal breast carcinomas. The correlation between topoisomerase II-alpha and c-erbB-2 expression, and its relationship with the clinicopathological factors such as the tumor size, lymph node metastasis, TNM stage, histological grade, nuclear grade, estrogen receptors and progesteron receptors was investigated. RESULTS: C-erbB-2 was expressed in 9 (20.9%) out of the 43 infiltrating ductal carcinoma cases. Among the prognostic factors, the tumor size, lymph node metastasis, tumor stage, nuclear grade, status of progesteron receptors and estrogen receptors did not significantly correlated with c-erbB-2 expression. The tumor size, lymph node metastasis, tumor stage, histological grade, and the absence of estrogen receptors displayed a significant relationship with the increase in the topoisomerase-alpha index. However, the topoisomerase II-alpha index did not correlate with the nuclear grade and the status of progesterone receptors. The topoisomerase II-alpha index was slightly higher in the c-erbB-2 positive expression cases compared to c-erbB-2 negative expression cases but this increase was not significant (P=0.503). CONCLUSION: These results suggest that topoisomerase II-alpha may play some role as a prognostic factor, but further investigation is needed.