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.

Clinical Significance of ReceptorInteracting Protein 3 and Parkin, Essential Molecules for Necroptosis, in Breast Cancer / 한국유방암학회지

Purpose@#Receptor-interacting protein 3 (RIP3) is the main initiator of necroptosis. Parkin prevents the formation of the RIP1–RIP3 complex by promoting polyubiquitination of RIP3. However, the mechanism by which necroptosis affects the clinical features of breast cancer and prognosis is not known. Here, we aimed to study the effect of necroptosis on the clinical features and prognosis of breast cancer by assessing the expression of RIP3 and Parkin. @*Methods@#Tissue microarrays (TMAs) were constructed from 257 cases of breast cancer.Immunohistochemistry was performed on 4-μm tissue sections from each TMA block. The χ2 test, Kaplan-Meier survival analysis with log-rank test, and Cox regression proportional hazard model were used for statistical analysis. @*Results@#Low RIP3 expression resulted in a large tumor size and high nuclear grade. Low RIP3 expression was correlated with human epidermal growth factor receptor 2 positivity, short overall survival (OS), and short disease-free survival (DFS). The triple negative breast cancer group with low RIP3 expression and lymph node (LN) positive group with low RIP3 expression had the shortest OS. High Parkin expression was associated with high histological grade, estrogen and/or progesterone receptor negativity, and lymphatic emboli, but was not correlated with OS and DFS. OS was correlated with LN metastasis and RIP3 loss and DFS with large tumor size, LN metastasis, and RIP3 loss. @*Conclusion@#Low RIP3 and high Parkin expression are associated with aggressive clinical features in breast cancer. RIP3, a molecular marker of necroptosis, is an independent factor associated with survival in breast cancer. Further in-depth studies are needed to investigate the role of necroptosis in breast cancer development, metastasis, and treatment in the future.

Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006) / 한국유방암학회지

Purpose@#In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. @*Methods@#In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. @*Results@#Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. @*Conclusion@#Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Clinical Significance of ReceptorInteracting Protein 3 and Parkin, Essential Molecules for Necroptosis, in Breast Cancer / 한국유방암학회지

Purpose@#Receptor-interacting protein 3 (RIP3) is the main initiator of necroptosis. Parkin prevents the formation of the RIP1–RIP3 complex by promoting polyubiquitination of RIP3. However, the mechanism by which necroptosis affects the clinical features of breast cancer and prognosis is not known. Here, we aimed to study the effect of necroptosis on the clinical features and prognosis of breast cancer by assessing the expression of RIP3 and Parkin. @*Methods@#Tissue microarrays (TMAs) were constructed from 257 cases of breast cancer.Immunohistochemistry was performed on 4-μm tissue sections from each TMA block. The χ2 test, Kaplan-Meier survival analysis with log-rank test, and Cox regression proportional hazard model were used for statistical analysis. @*Results@#Low RIP3 expression resulted in a large tumor size and high nuclear grade. Low RIP3 expression was correlated with human epidermal growth factor receptor 2 positivity, short overall survival (OS), and short disease-free survival (DFS). The triple negative breast cancer group with low RIP3 expression and lymph node (LN) positive group with low RIP3 expression had the shortest OS. High Parkin expression was associated with high histological grade, estrogen and/or progesterone receptor negativity, and lymphatic emboli, but was not correlated with OS and DFS. OS was correlated with LN metastasis and RIP3 loss and DFS with large tumor size, LN metastasis, and RIP3 loss. @*Conclusion@#Low RIP3 and high Parkin expression are associated with aggressive clinical features in breast cancer. RIP3, a molecular marker of necroptosis, is an independent factor associated with survival in breast cancer. Further in-depth studies are needed to investigate the role of necroptosis in breast cancer development, metastasis, and treatment in the future.

Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006) / 한국유방암학회지

Purpose@#In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. @*Methods@#In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. @*Results@#Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. @*Conclusion@#Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Use of positron emission tomography-computed tomography to predict axillary metastasis in patients with triple-negative breast cancer

PURPOSE: Axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) are important for staging of patients with node-positive breast cancer. However, these can be avoided in select micrometastatic diseases, preventing postoperative complications. The present study evaluated the ability of axillary lymph node maximum standardized uptake value (SUVmax) on positron emission tomography-computed tomography (PET-CT) to predict axillary metastasis of breast cancer.METHODS: The records of invasive breast cancer patients who underwent pretreatment (surgery and/or chemotherapy) PET-CT between January 2006 and December 2014 were reviewed. ALNs were preoperatively evaluated by PET-CT. Lymph nodes were dissected by SLNB or ALND. SUVmax was measured in both the axillary lymph node and primary tumor. Student t-test and chi-square test were used to analyze sensitivity and specificity. Receiver operating characteristic (ROC) and area under the ROC curve (AUC) analyses were performed.RESULTS: SUV-tumor (SUV-T) and SUV-lymph node (SUV-LN) were significantly higher in the triple-negative breast cancer (TNBC) group than in other groups (SUV-T: 5.99, P < 0.01; SUV-LN: 1.29, P=0.014). The sensitivity (0.881) and accuracy (0.804) for initial ALN staging were higher in fine needle aspiration+PET-CT than in other methods. For PET-CT alone, the subtype with the highest sensitivity (0.870) and negative predictive value (0.917) was TNBC. The AUC for SUV-LN was greatest in TNBC (0.797).CONCLUSION: The characteristics of SUV-T and SUV-LN differed according to immunohistochemistry subtype. Compared to other subtypes, the true positivity of axillary metastasis on PET-CT was highest in TNBC. These findings could help tailor management for therapeutic and diagnostic purposes.

Clinical Characteristics and Prognosis Associated with Multiple Primary Cancers in Breast Cancer Patients / 한국유방암학회지

PURPOSE: Breast cancer is one of the most common malignancies worldwide and the second most common cancer among Korean women. The prognosis of breast cancer is poor in patients with other primary cancers. However, there have been few clinical studies regarding this issue. Therefore, we analyzed the characteristics and prognosis of patients with breast cancer with multiple primary cancers (MPCs). METHODS: Data from the Korean Breast Cancer Society Registry were analyzed. Data from enrolled patients who underwent surgery for breast cancer were analyzed for differences in prognosis dependent on the presence of MPCs, and which MPC characteristics affected their prognosis. RESULTS: Among the 41,841 patients analyzed, 913 patients were found to have MPCs, accounting for 950 total MPCs. There was a significant difference in survival rates between the breast cancer only group and the MPC group. The 5-year survival rates were 93.6% and 86.7% and the 10-year survival rates were 87.5% and 70.4%, respectively. Among the 913 patients with MPCs, patients with two or more MPCs had significantly worse prognoses than patients with a single MPC. With respect to the time interval between breast cancer and MPC occurrence, patients with a 5-year or greater interval had significantly better prognoses than patients with less than 1 year between occurrences. Among MPCs, thyroid cancer was the most common primary cancer. However, this type was not related to the prognosis of breast cancer. Gynecologic cancer, colorectal cancer, upper gastrointestinal cancer, and lung cancer were related to breast cancer prognosis. CONCLUSION: MPCs were a poor prognostic factor for patients with breast cancer. Two or more MPCs and a shorter time interval between occurrences were worse prognostic factors. Although MPCs were a poor prognostic factor, thyroid cancer did not affect the prognosis of patients with breast cancer.

Pectoral nerve block (Pecs block) with sedation for breast conserving surgery without general anesthesia

Most regional anesthesia in breast surgeries is performed as postoperative pain management under general anesthesia, and not as the primary anesthesia. Regional anesthesia has very few cardiovascular or pulmonary side-effects, as compared with general anesthesia. Pectoral nerve block is a relatively new technique, with fewer complications than other regional anesthesia. We performed Pecs I and Pec II block simultaneously as primary anesthesia under moderate sedation with dexmedetomidine for breast conserving surgery in a 49-year-old female patient with invasive ductal carcinoma. Block was uneventful and showed no complications. Thus, Pecs block with sedation could be an alternative to general anesthesia for breast surgeries.

Erratum: Can We Omit Intraoperative Frozen Section According to the Result of the Preoperative Fine-needle Aspiration Cytology of a Thyroid Nodule? / 대한내분비외과학회지

We change the first author and corresponding author of this paper.

Can We Omit Intraoperative Frozen Section According to the Result of the Preoperative Fine-needle Aspiration Cytology of a Thyroid Nodule? / 대한내분비외과학회지

PURPOSE: Fine needle aspiration (FNA) is a useful preoperative diagnostic tool for thyroid nodule because of the high sensitivity and specificity. The aim of this study is to determine the necessity of intraoperative frozen section (IOFS) after fine needle aspiration. METHODS: Data of 534 patients with a single thyroid nodule who underwent thyroidectomy from June 2006 to August 2013 were reviewed retrospectively. FNA was performed preoperatively in all patients and IOFS was performed selectively according to the intraoperative findings and FNA results. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNA and IOFS for malignant nodules were analyzed. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FNA for malignant nodules were 100%, 95.5%, 99.8%, 100%, and 99.8%, respectively. All nodules diagnosed as benign by FNA were reaffirmed as benign nodules by permanent sections. When the result of FNA was suspicious for malignancy, specific features of preoperative ultrasound, including hypoechoic, size<10 mm showed high positive predictive value and accuracy (98%, 86.9%, and 100%, 78.7% respectively). CONCLUSION: Performance of IOFS was not necessary when the result of FNA was consistent with malignancy or benign. However when the result of FNA was non-diagnostic or atypia, IOFS should be performed for more accurate detection of malignancy. When the result of FNA is suspicious for malignancy, IOFS is restrictively useful for excluding benign nodules using the features of ultrasound. In addition, IOFS is not useful in finding malignant thyroid nodules when the result of FNA is follicular neoplasm.

BRAF mutation may predict higher necessity of postoperative radioactive iodine ablation in papillary thyroid cancer

PURPOSE: The primary aim of the present study was to analyze the association between high-risk clinicopathologic characteristics and the BRAFV600E mutation. METHODS: From March 2010 to September 2012, we performed analysis of the BRAF mutation (assessing V600E point mutation of BRAF gene, exon 15, on chromosome 7q34 by real-time polymerase chain reaction kit) from 499 papillary thyroid carcinoma (PTC) patients who underwent thyroidectomy. We analyzed the relation between the mutation and known clinicopathologic risk factors of PTC. RESULTS: BRAF mutations were found in 353 of 499 patients (70.7%). On univariate analysis, BRAF mutations were more frequently detected in patients with central lymph node metastasis (78.5% vs. 66.7%, P = 0.007) and classic PTC type (71.3% vs. 16.7%, P = 0.011). Patients with one or more aggressive pathologic feature such as lymph node metastasis, multifocality, and extrathyroidal extension showed higher BRAF mutation rate (73.5% vs. 62.3%, P = 0.022). BRAF mutation group showed more aggressive pathologic features, which is considered as higher necessity of radioactive iodine ablation (relative risk, 1.617; P = 0.035). CONCLUSION: This study found that BRAF mutation is associated with classic PTC and central lymph node metastasis and higher necessity of radioactive iodine ablation.

Multiple Symmetric Lipomatosis (Madelung's Disease) Presenting as Bilateral Huge Gynecomastia / 한국유방암학회지

Multiple symmetric lipomatosis (MSL), or Madelung's disease, is a rare disease of unknown etiology. It is characterized by the presence of loose adipose tissue deposits localized in the cervical region and upper body. MSL presenting as bilateral huge gynecomastia is an extremely rare phenomenon. The present report describes a case of MSL in a 66-year-old man. The patients presented with bilateral breast bulging. He had a history of cigarette and alcohol use. His condition was treated with a bilateral nipple-sparing mastectomy. MSL can present as a form of gynecomastia, for its accurate diagnosis and proper treatment of MSL, increasing awareness of the clinical characteristics of the disease is required, especially amongst breast surgeons. Herein, we review the literature and discuss the clinical characteristics, pathology, and surgical treatment of MSL.

Overexpression of MMP-9 and HIF-1alpha in Breast Cancer Cells under Hypoxic Conditions / 한국유방암학회지

PURPOSE: Hypoxia, which is a loss of oxygen in tissues, is a common condition in solid tumors due to the tumor outgrowing existing vasculature. Under hypoxic conditions, hypoxia-inducible factor (HIF)-1alpha rapidly accumulates and transactivates hundreds of genes, such as matrix metalloproteinases (MMPs). MMPs contribute to invasion and metastasis of tumor cells by degrading the surrounding basement membrane and extracellular matrix barriers, which enables the easy migration and spread of cancer cells. We examined whether hypoxia increases tumor cell invasion, and whether increased invasiveness was due to HIF-1alpha and MMP-9 expression. METHODS: Transwell invasion assays were performed to demonstrate whether hypoxia enhance tumor invasion by use of MDA-MB-231 breast cancer cells. An immunofluorescence assay was used to demonstrate expression of HIF-1alpha and MMP-9 under hypoxic conditions. Luciferase and ChiP assays were performed to demonstrate that MMP-9 promoter activity was regulated by HIF-1alpha. RESULTS: HIF-1alpha was stabilized under hypoxic conditions and stimulated MMP-9 expression, which affected the tumor invasiveness of breast cancer cells. HIF-1alpha transactivated the MMP-9 promoter by forming a transcriptional unit with p300, thus increasing expression of MMP-9 transcripts. Zymography indicated that MMP-9 had more gelatinase activity under hypoxic conditions than normoxic conditions. Furthermore, the small GTPase Ras was also activated in response to hypoxia, which then aids stabilization of HIF-1alpha, and in turn upregulates MMP-9 expression. We also demonstrate that MMP-9 is upregulated concurrently with HIF-1alpha in tumor tissues from patients with breast cancer. CONCLUSION: These results suggest that HIF-1alpha promotes cell invasion through a MMP-9-dependent mechanism and that future antitumor agents could be used to target HIF-1alpha and MMP-9.

A missense polymorphism (rs11895564, Ala380Thr) of integrin alpha 6 is associated with the development and progression of papillary thyroid carcinoma in Korean population / 대한외과학회지

PURPOSE: Integrins play crucial roles in the pathogenesis of papillary thyroid carcinoma (PTC). The aim of this study was to investigate whether two single nucleotide polymorphisms (SNPs) (rs2141698, -1687A/G; rs11895564, Ala380Thr) of the integrin alpha 6 (ITGA6) gene are associated with the development and clinicopathologic characteristics of PTC such as the size ( or =1 cm), number (unifocality and multifocality), location (one lobe and both lobes), extrathyroid invasion, and cervical lymph node metastasis. METHODS: We enrolled 104 PTC patients and 318 control subjects. Genotypes of each SNP were determined by direct sequencing. SNPStats, SNPAnalyzer, and Helixtree programs were used to evaluate odds ratios (ORs), 95% confidence intervals (CIs), and P-values. Multiple logistic regression models were performed to analyze genetic data. RESULTS: A missense SNP rs11895564 was associated with the development of PTC. The A allele frequency of rs11895564 was higher in PTC patients than in controls (13.5% vs. 7.1%; P = 0.005; OR, 2.04; 95% CI, 1.24 to 3.37). In the clinicopathologic characteristics, the A allele frequency of rs11895564 showed difference in the size (19.6% in or =1 cm; P = 0.010; OR, 0.30; 95% CI, 0.12 to 0.75) and number (8.5% in unifocality vs. 20.8% in multifocality; P = 0.015; OR, 2.85; 95% CI, 1.23 to 6.59) of PTC. CONCLUSION: These results suggest that the A allele of rs11895564 (Ala380Thr) in ITGA6 may be a risk factor of PTC, and also contribute to the progression of PTC in the Korean population.

A missense polymorphism (rs11895564, Ala380Thr) of integrin alpha 6 is associated with the development and progression of papillary thyroid carcinoma in Korean population / 대한외과학회지

PURPOSE: Integrins play crucial roles in the pathogenesis of papillary thyroid carcinoma (PTC). The aim of this study was to investigate whether two single nucleotide polymorphisms (SNPs) (rs2141698, -1687A/G; rs11895564, Ala380Thr) of the integrin alpha 6 (ITGA6) gene are associated with the development and clinicopathologic characteristics of PTC such as the size ( or =1 cm), number (unifocality and multifocality), location (one lobe and both lobes), extrathyroid invasion, and cervical lymph node metastasis. METHODS: We enrolled 104 PTC patients and 318 control subjects. Genotypes of each SNP were determined by direct sequencing. SNPStats, SNPAnalyzer, and Helixtree programs were used to evaluate odds ratios (ORs), 95% confidence intervals (CIs), and P-values. Multiple logistic regression models were performed to analyze genetic data. RESULTS: A missense SNP rs11895564 was associated with the development of PTC. The A allele frequency of rs11895564 was higher in PTC patients than in controls (13.5% vs. 7.1%; P = 0.005; OR, 2.04; 95% CI, 1.24 to 3.37). In the clinicopathologic characteristics, the A allele frequency of rs11895564 showed difference in the size (19.6% in or =1 cm; P = 0.010; OR, 0.30; 95% CI, 0.12 to 0.75) and number (8.5% in unifocality vs. 20.8% in multifocality; P = 0.015; OR, 2.85; 95% CI, 1.23 to 6.59) of PTC. CONCLUSION: These results suggest that the A allele of rs11895564 (Ala380Thr) in ITGA6 may be a risk factor of PTC, and also contribute to the progression of PTC in the Korean population.

Chemotherapy Response Assay Test and Prognosis for Breast Cancer Patients Who Have Undergone Anthracycline- and Taxane-Based Chemotherapy / 한국유방암학회지

PURPOSE: A chemotherapy response assay test is performed to evaluate the degree of tumor growth inhibition by a chemotherapeutic agent. Several studies have been done on its usefulness; however, to the best of our knowledge, only a few studies concerning the relationship between chemotherapy response assay test results and breast cancer patients' prognoses have been conducted. Thus, we performed this study to analyze this relationship. METHODS: Among breast cancer patients who underwent curative surgery and neoadjuvant or adjuvant chemotherapy between August 2004 and December 2009, 102 were enrolled in this study. Chemotherapeutic regimens for patients were doxorubicin plus taxane or doxorubicin plus cyclophosphamide followed by taxane. We divided these patients into two groups (sensitive group [n=19] and resistant group [n=83]) and analyzed the relationship between chemosensitivity results and patient prognosis. RESULTS: The sensitive group was associated with poor disease-free survival (DFS) (p=0.003) and overall survival (OS) (p<0.001). No significant differences were observed in tumor histology (p=0.548), tumor size (p=0.479), number of metastatic lymph nodes (p=0.326), histologic grade (p=0.077), or nuclear grade (p=0.216) between the two groups. However, in respect to molecular subtype, the HER2-positive type and triple negative breast cancer were more frequently observed in the sensitive group (p=0.001). In a univariate and multivariate analysis for DFS, doxorubicin sensitivity was significantly associated with a poor prognosis (p<0.05). CONCLUSION: Better chemosensitivity results are associated with a poor prognosis in breast cancer patients who have undergone anthracycline- and taxane-based chemotherapy, however, examination of additional cases and the use of a longer study period are needed.

A Case of Small Bowel GIST Initially Suspected as Peritoneal Seeding of Gastric Cancer

Gastrointestinal stromal tumors (GISTs) constitute the most common primary mesenchymal tumors of the digestive tract and characteristically express c-kit (CD117). GISTs are the most common non-epithelial tumor of the GI tract and frequently originate from the stomach and small bowel. Specifically, the synchronous occurrence of a GIST with other epithelial tumors is rarely reported. Recently, we discovered one case of a concurrent gastric cancer and a small bowel GIST that was initially suspected to be peritoneal seeding from gastric cancer. The patient was initially admitted with epigastric pain. Gastric cancer with peritoneal seeding was suspected after an evaluation. Following a laparoscopic examination, a distal gastrectomy with D2 lymph node dissection and small-intestine segmental resection was performed. The final pathologic diagnosis was early gastric cancer and high-risk small bowel GIST. The patient refused adjuvant therapy for the GIST, and currently shows no other marked indisposition. He has been disease-free for 14 months.

Cyclooxygenase (COX)-1, Cyclooxygenase (COX)-2 and E-cadherin Expression in Colorectal Cancer Patients with Hepatic Metastasis

PURPOSE: Recent studies have shown that cyclooxygenase (COX)-2 may be involved in colorectal carcinogenesis. In this study, we evaluate the differences of COX-2 expression in patients with synchronous and metachronous hepatic metastasis of colorectal cancer. In addition, the expression of COX-1 and E-cadherin were also evaluated. METHODS: Paraffin embedded blocks were obtained from 41 patients who underwent surgery for colorectal cancer with hepatic metastasis. Samples from primary colorectal cancer, synchronous and metachronous hepatic lesions were stained by immunohistochemistry for monoclonal antibody against COX-1, COX-2, and E-cadherin. RESULTS: In colonic COX-1 expression, there was no significant difference in the degree of COX-1 expression between primary colorectal cancer with synchronous hepatic metastasis and that of metachronous hepatic metastasis (P=0.507). In colonic COX-2 and E-cadherin expression, the degree of COX-2 expression was not different between the two groups. But, the patient survival rate in the positive group of COX-1 and COX-2 expression was lower than in the negative group, respectively (P=0.023, P=0.006). CONCLUSION: The degree of colonic COX-1 and COX-2 expression has an impact on prognosis in synchronous and metachronous hepatic metastasis. Further large-scale study is necessary to determine the meaning of COX-2 expression in colorectal cancer.

Uncoupling Protein 2 (UCP2) and p53 Expression in Invasive Ductal Carcinoma of Breast

BACKGROUND: Uncoupling protein 2 (UCP2) is a recently identified mitochondrial inner membrane anion carrier and a negative regulator of reactive oxygen species production. In this study, we evaluated the characteristics and relationships of UCP2 and p53 expression in breast cancer tissues. METHODS: Tissue microarray slides from 107 cases of invasive ductal carcinoma of the breast were constructed, UCP2 and p53 immunohistochemical staining was conducted, and clinicopathological correlations were investigated. RESULTS: UCP2 expression in invasive ductal carcinoma was high in 53 cases (49.5%), while p53 expression in invasive ductal carcinoma was high in 37 cases (34.6%). UCP2 expression was correlated significantly with histological grade (p = 0.038) and mitotic count (p = 0.050). UCP2 expression was correlated significantly with p53 expression in invasive ductal carcinoma of the breast (p = 0.045). UCP2 expression (p = 0.8308) and p53 expression (p = 0.3292) showed no significant difference for the overall survival rate in patients with invasive ductal carcinoma. CONCLUSIONS: UCP2 expression in invasive ductal carcinoma increased proportionally with histological grade and mitotic count. High UCP2 expression in invasive ductal carcinoma was observed in conjunction with high p53 expression.

Diagnosis of Papillary Thyroid Cancer via Detection of BRAF Mutation on Fine Needle Aspiration Cytology Slides / 대한내분비외과학회지

PURPOSE: The prevalence rate of the BRAF mutation in papillary thyroid cancer (PTC) is as high as about 52 to 83% in Korea. Preoperative detection of BRAF mutation on fine needle aspiration cytology (FNAC) slides may help the surgeon make better therapeutic decisions. The present study aims to assess the feasibility of the mutant allele specific amplification (MASA) and restriction fragment length polymorphism (RFLP) method with using conventional FNAC slides and we also wanted to evaluate the clinical role of preoperatively detecting BRAF mutation. METHODS: We extracted the genomic DNA from 59 FNAC slides and performed direct sequencing (DS) for detecting BRAF mutation. We could use only 17 slides for the MASA method and 6 slides for the RFLP method due to the shortage of extracted DNA. Additionally, we retrospectively analyzed the cases for which a histological diagnosis could be made. RESULTS: Genomic DNA was extracted from 23 out of the 59 FNAC slides. The BRAF mutation status could be assessed via DS in 33 out of the 59 FNAC slides. The concordance between the MASA method and DS and the RFLP method and DS was 36.3% and 66.7% respectively. The positive and negative predictive value of the 13 indeterminate nodules was 87.5% and 20%, respectively. We could not find any association between the BRAF mutations and the alleged risk factors of PTC. CONCLUSION: We believe that the purity and the amount of the DNA template must be increased to detect BRAF mutation with using a FNAC slide. Preoperative detection of the BRAF mutation on a FNAC slide may refine the cytological diagnosis, but the application of assessing BRAF mutation as a prognostic marker is debatable.