Ja Seong Bae

Catholic University of Korea, Seoul, Seoul, South Korea

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Publications (29)57.79 Total impact

  • Article: Molecular genotyping of follicular variant of papillary thyroid carcinoma correlates with diagnostic category of fine needle aspiration cytology: values of RAS mutation testing.
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    ABSTRACT: Background: The follicular variant of papillary thyroid carcinoma (FVPTC) presents distinct histologic subtypes and molecular genotyping. The preoperative diagnosis of FVPTC through fine needle aspiration cytology (FNAC) is challenging. Methods: We reviewed 59 archival thyroid FNAC specimens of surgically confirmed FVPTC according to histologic subtype: encapsulated FVPTC (n=30) and infiltrative FVPTC (n=29). Galectin-3 immunostaining and molecular analyses for BRAF and three RAS genes (NRAS, HRAS, and KRAS) were performed. Results: FNAC diagnoses of FVPTC included benign (5%), atypia of undetermined significance (19%), follicular neoplasm/suspicious for follicular neoplasm (14%), suspicious for PTC (29%), and PTC (34%). Galectin-3 immunostaining was positive in 50% of FNAC specimens. A BRAF mutation was only found in 14 (24%) tumors with the FNAC diagnosis of PTC or suspicious for PTC; 13 cases with the usual c.1799T>A (p.V600E) mutation and one case with a 3 base-pair deletion (c.1799_1801delTGA) resulting in a deletion of lysine at codon 601 and a valine-to-glutamate substitution at codon 600 (p.V600_K601>E) while preserving the reading frame of the gene. A BRAF K601E mutation was not found. RAS mutations were observed in 18 (33%) tumors (NRAS, 22%; HRAS, 6%; KRAS, 6%). Mutations of the three RAS genes were detected in codon 61 but not in codons 12 and 13. There was a decreasing trend of RAS mutation rate associated with increasing in risk of being malignant from benign to malignant FNAC diagnostic categories. The triage efficacy of FNAC to make a recommendation for surgery was 73% for encapsulated tumors and 79% for infiltrative tumors. Addition of galectin-3 or the BRAF test to FNAC showed no significant improvement in the triage efficacy. However, RAS mutations significantly improved the triage efficacy of FNAC. There was no significant difference in the triage efficacy of FNAC, galectin-3 expression, and the prevalence of somatic mutations between encapsulated and infiltrative tumors. Conclusion: Thyroid FNAC has a low sensitivity for the detection of FVPTC regardless of histologic subtype. Encapsulated FVPTC and infiltrative FVPTC have similar molecular profiles and rates of galectin-3 expression. RAS mutational analysis is more useful than BRAF testing to improve the triage efficacy of FNAC for FVPTC.
    Thyroid: official journal of the American Thyroid Association 04/2013; · 2.60 Impact Factor
  • Article: Breast cancer after kidney transplantation: a single institution review.
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    ABSTRACT: BACKGROUND: Improvements in immunosuppression have resulted in long life expectancy of kidney transplants. Unfortunately, the incidence of post-transplant malignancy (PTM) is increasing. The aim of this study was to evaluate the nature and stage-specific prognosis of post-transplant breast cancer (PTBC) compared with breast cancer in the general population, and to suggest optimal treatment strategies. METHODS: A prospectively collected database of 2,139 consecutive kidney transplant patients was reviewed;11 of the patients developed breast cancer. These 11 PTBC cases underwent operations between 1999 and 2011. Next, 2,554 breast cancer patients treated in the same period were reviewed. Kaplan--Meier curves and the log-rank test were used to assess stage-specific survival of breast cancer in our hospital. RESULTS: In total, 142 cases experienced post-transplant malignancy (PTM; 6.6%) and 11 (0.5%) developed PTBC. No one required an adjusted dose of immunosuppressive agent. Two stage III patients died. For all breast cancer patients, 5-year survival by stage was 97.7% for stage I, 92.9% for stage II, 78.6% for stage III, and 49.9% for stage IV. The 5-year survival for expected stage III-specific survival was 66.7% and no significant statistical difference was seen compared to that of the total breast cancer patients (P = 0.213). CONCLUSIONS: The prognosis of PTBC was comparable to that of the general population. These results suggest that the use of immunosuppressants per se does not adversely affect breast cancer.
    World Journal of Surgical Oncology 03/2013; 11(1):77. · 1.12 Impact Factor
  • Article: Combination of Initial Stimulation Thyroglobulins and Staging System by Revised ATA Guidelines Can Elaborately Discriminate Prognosis of Patients With Differentiated Thyroid Carcinoma After High-Dose Remnant Ablation.
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    ABSTRACT: The aim of this study was to evaluate prognostic role of thyroglobulin (Tg) levels at the time of ablation (A-Tg) and stimulation Tg levels at 6-12 months after remnant ablation (S-Tg) combined with revised American Thyroid Association (ATA) guidelines risk stratification. Data of 359 patients (median follow-up duration: 66.3 months) with papillary thyroid carcinoma who had high-dose remnant ablation were analyzed. The cutoff value of A-Tg to predict the persistent/recurrent disease was calculated by receiver operating characteristic curve analysis. In each risk group by ATA guidelines, the association of A-Tg with persistent/recurrent disease was evaluated. The role of A-Tg and ATA risk stratification in each S-Tg group (group with S-Tg <2 ng/mL, 2-10 ng/mL, or >10 ng/mL) was also evaluated. Tg response was determined by the difference between A-Tg and S-Tg with consideration of the dose of radioactive iodine ablation. A-Tg above 5.22 ng/mL was associated with persistent/recurrent disease in all risk groups by ATA guidelines. A-Tg above the cutoff value and ATA risk assessment was related to persistent/recurrent disease in patients with S-Tg 2 to 10 ng/mL (P = 0.003) and S-Tg above 10 ng/mL (P = 0.019). However, no difference in the incidence of persistent/recurrent disease was found according to Tg response. The scoring system made up of A-Tg, S-Tg, and ATA staging showed elaborate discrimination of prognosis. Risk stratification using combined scoring with initial stimulated Tg levels, including A-Tg and S-Tg, and staging system by revised ATA guidelines can effectively predict persistent/recurrent disease in patients with papillary thyroid carcinoma.
    Clinical nuclear medicine 09/2012; 37(11):1069-74. · 3.92 Impact Factor
  • Article: Present condition analysis of physician assistant in Korea.
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    ABSTRACT: This study intended to identify the need for the legalization and development of a systematic program for physician assistants (PAs) by understanding the actual state of PA operation in hospitals. In 114 hospitals assigned as resident training hospitals for surgery, a survey was conducted on the personnel working as PAs in those hospitals; the survey included general personal information, working conditions, training time, and satisfaction. A total of 192 PAs in surgery at 35 hospitals responded to the survey. The types of PAs are Surgical Assistant, Clinical Physician Assistant, Wound Ostomy Care Nurse, Coordinator, and Clinical Research Coordinator. Types of work PAs preformed are surgical assistance, wound dressing, educating patients, overlooking consultation, doing paper works, writing operation records, and confirming examination results which were ordered. The satisfaction level for the position which PAs hold were 29.1% and and satisfaction level which doctors see towards PA was 15%. The role and the job descriptions of PAs are not clear cut, there are many discrepancies among hospitals we studied. As a result, legalization and the implementation of standardized role of PAs will lead to increase level of satisfactions in the work force and the quality of work which PAs perform will be greater.
    Journal of Korean medical science 09/2012; 27(9):981-6. · 0.84 Impact Factor
  • Article: Absence of Galectin-3 Immunostaining in Fine-Needle Aspiration Cytology Specimens from Papillary Thyroid Carcinoma Is Associated with Favorable Pathological Indices.
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    ABSTRACT: Background: Galectin-3 (G3) immunostaining of fine-needle aspiration (FNA) samples from thyroid nodules is very useful for the diagnosis of malignancy. The objective of the present study was to determine whether the absence of G3 immunostaining in preoperative FNA samples is associated with favorable clinicopathological parameters, including lymph node (LN) metastasis, in papillary thyroid carcinoma (PTC). Methods: The records of 868 patients with PTC who had prethyroidectomy ultrasonography-guided FNA with G3 immunostaining between January 2006 and December 2009 were retrospectively reviewed. G3 immunostaining was considered positive if the percentage of tumor cells showing definite cytoplasmic immunostaining exceeded 5%. Patients who had negative G3 immunostaining of FNA samples were assigned to the G3-negative (G3N) group; whereas those who had positive G3 immunostaining were assigned to the G3-positive (G3P) group. Results: There were 92 patients who were assigned to the G3N group (10.6%) because of the negative staining for G3 in the preoperative FNA samples from their thyroid nodules. The proportion of PTC subtypes in the G3N and G3P groups was similar (p=0.376). There was less frequent thyroid capsular invasion (46.7% vs. 66.5%, p<0.001), extrathyroidal extension (28.3% vs. 48.5%, p<0.001), and LN metastasis (22.2% vs. 48.7%, p<0.001) in the G3N group than the G3P group. In multivariate regression analysis, G3N expression predicted a lower risk of LN metastasis (odds ratio=0.37, 95% confidence interval 0.18-0.78) after adjustment for other clinicopathological parameters. Over a median follow-up of 33 months, no association was observed between G3N and disease-free survival. Conclusion: The absence of G3 expression in FNA samples from PTC is associated with pathological parameters considered less aggressive than is the case for PTCs with G3 expression, including being a negative predictor of negative LN involvement. Long-term follow-up studies, however, are needed to verify whether G3N patients have lower recurrence and mortality rates.
    Thyroid: official journal of the American Thyroid Association 08/2012; · 2.60 Impact Factor
  • Article: DHPLC is a highly sensitive and rapid screening method to detect BRAF(V600E) mutation in papillary thyroid carcinoma.
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    ABSTRACT: The BRAF(V600E) mutation has been reported to occur in 30% to 80% of papillary thyroid carcinomas (PTCs). Although direct sequencing is the method most commonly used to identify mutations, this technique is not sensitive enough to accurately detect low level mutation. To determine the optimal diagnostic method for detecting the BRAF(V600E) mutation in PTC, we compared the diagnostic efficacy of four representative detection methods in formalin-fixed paraffin-embedded thyroid tissues obtained from 40 patients diagnosed with PTC. To detect the BRAF(V600E) mutation, we amplified exon 15 of the BRAF gene and performed mutational analysis with direct sequencing, denaturing high-performance liquid chromatography (DHPLC), pyrosequencing and colorimetric assay. The BRAF mutation was detected in 33 cases (82.5%) by DHPLC, 23 cases (57.5%) by direct sequencing, 22 cases (55.0%) by pyrosequencing, and 37 cases (92.5%) by colorimetric assay. The sensitivity, negative predictive value and accuracy of DHPLC were 100%. The specificity and positive predictive values for DHPLC, direct sequencing and pyrosequencing were 100%, and for colorimetric assay they were 14.3% and 83.8%, respectively. The kappa value for DHPLC was a perfect 1.0, which was superior to the other methods. In conclusion, DHPLC is a sensitive, specific and accurate method for detecting the BRAF(V600E) mutation, especially low level mutation, in PTC.
    Experimental and Molecular Pathology 06/2012; · 2.42 Impact Factor
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    Article: Multidisciplinary team approach in breast cancer: a nationwide survey in Korea.
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    ABSTRACT: This assesses the current workings of multidisciplinary team (MDT) meetings across Korea through surgeons' reports and their current commitments to MDT meetings pertaining to breast cancer, and to determine any perceived areas of potential improvement. A questionnaire was sent out to 307 members of The Korean Breast Cancer Society (KBCS) who worked at comprehensive or university medical centers in Korea. The mailing lists of the KBCS members were obtained with the approval of the society. From December 2008 to February 2009, the survey was distributed by surface and electronic mail, with an initial mailing followed by another distribution to non-responders eight weeks later. Sixty-five individuals (21.2%) returned the completed survey. Of these, 38 responders (62.3%) participated in MDT meetings. Most (97.4%) breast health specialists regarded MDT meetings as an effective method for treatment planning. Most responders (94.7%) reported that the MDT leader was a breast surgeon. The MDT approach is perceived as an effective method for breast cancer treatment planning and is a feature in most major centers in Korea. Further work is needed to ensure that the MDT approach operates as intended and that all breast cancer patients have access to an MDT.
    Journal of the Korean Surgical Society. 06/2012; 82(6):340-6.
  • Article: Mutational patterns and novel mutations of the BRAF gene in a large cohort of Korean patients with papillary thyroid carcinoma.
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    ABSTRACT: Background: BRAF mutation is the most common genetic event in papillary thyroid carcinoma (PTC); however, the prevalence and patterns of the mutation vary worldwide. We investigated the frequency and type of BRAF mutations based on the histologic subtypes in a large cohort of Korean patients with PTC. A total of 1041 consecutive PTCs were classified according to histologic subtypes. BRAF mutations were examined by denaturing high-performance liquid chromatography and direct sequencing. Rare complex mutations were confirmed by molecular cloning of polymerase chain reaction amplicons and sequencing of the products. BRAF mutations were found in 839 (80.6%) of 1041 patients with PTC. The histologic subtype-specific prevalence of BRAF mutation was as follows: 85.3% (249/292) were classic, 45.8% (11/24) were follicular, 79.9% (576/721) were microcarcinoma, and 75.0% (3/4) were other variants. In addition to the usual c.1799T>A mutation, we identified other four mutation types: c.[1795_1796insA;1770_1795dup26], c.[1742-10T>C;1799T>A] and c.[1796C>G;1799T>A], and c.1799_1800TG>AA, respectively. The former three were novel mutations in thyroid tumors. Within the series of microcarcinoma variants, the BRAF mutation rate was lower in tumors with follicular morphology than those with nonfollicular types (66.7% vs. 80.9%, p=0.0145). Out of 1041 Korean patients with PTC, 0.4% had rare types of BRAF mutation and three new somatic mutations were identified. The BRAF mutation rate was quite low in PTC with follicular morphology regardless of tumor size. However, the prevalence of BRAF mutation in microcarcinoma and follicular variants of PTC is relatively high in Korea and its analysis may be clinically useful for managing the patients.
    Thyroid: official journal of the American Thyroid Association 04/2012; 22(8):791-7. · 2.60 Impact Factor
  • Article: Role of [(18)F]-fluorodeoxy-D-glucose positron emission tomography and computed tomography in the early detection of persistent/recurrent thyroid carcinoma in intermediate-to-high risk patients following initial radioactive iodine ablation therapy.
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    ABSTRACT: Positron emission tomography/computed tomography (PET/CT) scan has a role in the surveillance of patients with a history of thyroid carcinoma. Its efficacy after remnant ablation as far as detecting persistent or recurrent thyroid carcinoma before other surveillance methods is not known, however. In intermediate-to-high risk thyroid carcinoma patients we studied whether PET/CT scan, performed 6-12 months after the first remnant ablation, could provide more information than ultrasonography (US) and thyrotropin-stimulated serum thyroglobulin (Tg) determination with diagnostic whole-body scan (DxWBS). We studied 71 subjects with differentiated thyroid cancer (DTC) who were intermediate-to-high risk for persistent/recurrent disease and who had received PET/CT scan, US, and DxWBS simultaneously with stimulated Tg levels 6-12 months after remnant ablation. To evaluate the diagnostic efficacy of PET/CT scan, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. Ten subjects (14%) had persistent/recurrent disease detected 6-12 months after remnant ablation. Persistence/recurrence was detected in nine (12.7%) of these patients by conventional methods, including US and DxWBS, along with stimulated Tg levels. The remaining case was detected solely by a PET/CT scan, which showed a mediastinal prevascular lesion; this was confirmed by a therapeutic WBS after additional radioiodine therapy. Among the six patients whose PET/CT scan showed positive results, five had persistent/recurrent disease. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of PET/CT scan for detecting persistent/recurrent thyroid carcinoma were 50%, 98.4%, 83.3%, 92.3%, and 91.5%, respectively. In intermediate-to-high risk patients with DTC seen 6-12 months after their first remnant ablation, there is almost no complementary role for adding a PET/CT scan to conventional follow-up methods, an US and a DxWBS simultaneously with stimulated Tg levels.
    Thyroid: official journal of the American Thyroid Association 02/2012; 22(2):157-64. · 2.60 Impact Factor
  • Article: Mutational patterns and novel mutations of BRAF gene in a large cohort of Korean patients with papillary thyroid carcinoma.
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    ABSTRACT: Background: BRAF mutation is the most common genetic event in papillary thyroid carcinoma (PTC); however, the prevalence and patterns of the mutation vary worldwide. We investigated the frequency and type of BRAF mutations based on the histologic subtypes in a large cohort of Korean patients with PTC. Methods: A total of 1041 consecutive PTCs were classified according to histologic subtypes. BRAF mutations were examined by denaturing high performance liquid chromatography and direct sequencing. Rare complex mutations were confirmed by molecular cloning of PCR amplicons and sequencing of the products. Results: BRAF mutations were found in 839 (80.6%) of 1041 patients with PTC. The histologic subtype specific prevalence of BRAF mutation was as follows: 85.3% (249/292) in classic, 45.8% (11/24) in follicular, 79.9% (576/721) in microcarcinoma, and 75.0% (3/4) in other variants. In addition to the usual c.1799T>A mutation, we identified other four mutation types: c.[1795_1796insA;1770_1795dup26], c.[1742-10T>C;1799T>A] and c.[1796C>G;1799T>A], and c.1799_1800TG>AA, respectively. The former three were novel mutations in thyroid tumors. Within the series of microcarcinoma variants, BRAF mutation rate was lower in tumors with follicular morphology than those with non-follicular types (66.7% vs 80.9%, p = 0.0145). Conclusion: Out of 1041 Korean patients with PTC, 0.4% had rare types of BRAF mutation and three new somatic mutations were identified. The BRAF mutation rate was quite low in PTC with follicular morphology regardless of tumor size. However, the prevalence of BRAF mutation in microcarcinoma and follicular variants of PTC is relatively high in Korea and its analysis may be clinically useful for managing the patients.
    Thyroid: official journal of the American Thyroid Association 01/2012; · 2.60 Impact Factor
  • Article: Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer.
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    ABSTRACT: Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer. In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR), and human epithelial receptor-2 (HER2) were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC) according to ER, PR, and HER2 status. Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes. Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.
    World Journal of Surgical Oncology 01/2012; 10:4. · 1.12 Impact Factor
  • Article: Notch1 receptor as a marker of lymph node metastases in papillary thyroid cancer.
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    ABSTRACT: Notch functions as an oncogene or tumor suppressor according to the type of malignancy, and the BRAF(V600E) mutation is commonly observed in thyroid cancer. However, the role of Notch and BRAF(V600E) in papillary thyroid cancer (PTC) is unclear. This study sought to elucidate the clinicopathological characteristics in patients with PTC regarding the expression of Notch1/Notch3 receptors and BRAF(V600E) mutation. Clinicopathological characteristics were evaluated according to the Notch1/Notch3 receptors and BRAF(V600E) mutation in 187 patients with PTC who underwent definitive surgery. Expression of the Notch1 receptor was significantly associated with poor prognostic markers including large tumor size, nodal metastasis, capsular invasion, and extrathyroidal extension. However, there was no significant association between the clinicopathological characteristics and Notch3 receptor expression/BRAF(V600E) mutation. In multivariate analysis, Notch1 receptor expression showed a significant relationship with lymph node metastasis (P = 0.04). Notch1 receptor may be a predictor of lymph node metastasis and may be related to poor prognostic markers in patients with PTC. Further investigation of Notch1 receptor may further the understanding of the pathogenesis of nodal metastasis in PTC.
    Cancer Science 11/2011; 103(2):305-9. · 3.33 Impact Factor
  • Article: Comparison of surgical outcomes between endoscopic and robotic thyroidectomy.
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    ABSTRACT: Gasless transaxillary endoscopic thyroidectomy offers a distinct advantage over the conventional open operation because it leaves no visible neck scar. Indications have expanded with the development of new surgical techniques and instruments. However, because of the two-dimensional view and the nonflexible instruments, this procedure is not easily amenable for total thyroidectomy. So, robotic surgery has been introduced and offers improved visualization and dexterity. But, it remains unclear whether robotic thyroidectomy offers any potential benefits over endoscopic thyroidectomy. The aim of this present study was to determine whether robotic surgery is superior to endoscopic surgery through a comparison of surgical outcomes. Between May 2009 and February 2011, 165 patients underwent endoscopic thyroidectomy (endoscopy group) and 46 patients underwent robotic thyroidectomy (robot group). A gasless transaxillary approach was used in both groups. The two groups were compared in terms of patient characteristics, perioperative clinical results, pathologic findings, and postoperative complication. Both patient groups were similar in terms of patient characteristics, mean number of retrieved central lymph nodes, pathological features, length of hospital stays, postoperative complication rate, and serum Tg level. However, the mean total operation time for thyroidectomy was 126.2 ± 37.84 min in the endoscopy group and 179.6 ± 44.34 min in the robot group (P < 0.001). Postoperative total drainage for lobectomy was 153.3 ± 45.64 for the endoscopy group and 179.9 ± 49.15 for the robot group (P = 0.031). Cost effectiveness is also an important consideration when evidence for predominance of two surgical techniques is lacking. The mean cost of robotic thyroidectomy was $6,655, compared with $829 for endoscopic thyroidectomy (P < 0.001). There was no significant difference in postoperative complications as hypocalcemia, recurrent laryngeal nerve injury, chyle leakage and tracheal injury in the two groups (P = 0.332). Robotic thyroidectomy was lengthier in duration than endoscopic thyroidectomy, more costly, and associated with increased postoperative drainage with no improvement in oncologic outcomes or complication rates. Therefore our data do not support any advantage of robotic surgery over endoscopic surgery.
    Journal of Surgical Oncology 09/2011; 105(7):705-8. · 2.10 Impact Factor
  • Article: Performing contralateral central lymph node dissection in papillary thyroid carcinoma: a decision approach.
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    ABSTRACT: Substantial controversy exists over the role of prophylactic neck dissection for patients with papillary thyroid carcinoma (PTC). We hypothesized that a therapeutic strategy of performing a routine intraoperative frozen section of the ipsilateral central lymph node (CLN) after elective ipsilateral CLN dissection (CLND) for all unilateral PTC and then performing a contralateral CLND if the frozen section is positive for malignancy would reduce morbidity compared to a therapeutic strategy of routine bilateral CLND. In a group of 419 patients with PTC undergoing thyroidectomy during study the period, the 203 patients who had unilateral PTC and no evidence of adenopathy on ultrasonography were prospectively enrolled in our nonrandomized study that was performed between March 2009 and February 2010. Patients underwent a total thyroidectomy if tumor size was over 1 cm or extrathyroidal was detected on ultrasonography. Patients underwent a subtotal or near-total thyroidectomy if tumor size was <1 cm and additional benign tumor existed on contralateral lobe. There were 25 patients who had a unilateral CLND with a subtotal or near-total thyroidectomy, and 178 patients who underwent a unilateral or bilateral CLND with a total thyroidectomy. There was no difference in the rate of major complications between unilateral CLND group and bilateral CLND group. The rate of transient hypocalcemia was 31.8% in the unilateral CLND group and 45.7% in the bilateral CLND group (p = 0.084). The rate of voice change was 7.6% in the unilateral CLND group 4.3% in the bilateral CLND group (p = 0.438). The ratio of malignant to all nodes retrieved was 0.5/7.88 in the unilateral CLND group and 5.13/17.20 in the bilateral CLND group. There was 78.3% sensitivity and 100% specificity for frozen biopsy of ipsilateral CLN to predict contralateral CLN metastasis. A positive ipsilateral CLN frozen biopsy was significantly associated with contralateral CLN metastasis (p < 0.001), as was younger age (p = 0.002) and existence of extrathyroidal extension (p = 0.031), each on univariate analysis. In patients with unilateral PTC, routine ipsilateral CLND with intraoperative reading of the frozen section can be employed to assess the risk of contralateral CLN metastasis. This information should be of value in deciding whether to perform contralateral CLND or not.
    Thyroid: official journal of the American Thyroid Association 08/2011; 21(8):873-7. · 2.60 Impact Factor
  • Article: Is the BRAF(V600E) mutation useful as a predictor of preoperative risk in papillary thyroid cancer?
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    ABSTRACT: Recent studies have shown that a BRAF(V600E) reflects poor prognosis, mainly in Western countries. However, some clinicians in Japan have suggested that the BRAF(V600E) mutation is not associated with a poor prognosis. Therefore, we investigated a relationship between BRAF(V600E) mutation and clinicopathologic factors. From September 2008 to December 2009, we performed routine analysis of the BRAF(V600E) mutation using thyroid cancer tissue from 424 patients who underwent thyroidectomy with cervical lymph node dissection. The BRAF(V600E) mutation was found in 335 of 424 cases (79%) and was higher in classic papillary thyroid carcinoma (PTC) (79.7%) than in the follicular variant of PTC (62.5%) (P = .019). On univariate analysis, the BRAF(V600E) mutation was associated with extrathyroidal extension (P = .009) and variants of PTC (P = .019), but a high-risk Metastasis, Patient Age, Completeness of resection, local Invasion and Tumor Size (MACIS) score (≥ 6) (P = .146) and lymph node metastasis (P = .628) were not significantly associated with the BRAF(V600E) mutation. Multivariate analysis showed that extrathyroidal extension is independently associated with the BRAF(V600E) mutation (relative ratio: 2.466; 95% confidence interval, 1.213-5.011; P < .013). It is not clear that the BRAF(V600E) mutation is useful for prediction of poor prognosis of PTC.
    American journal of surgery 07/2011; 203(4):436-41. · 2.36 Impact Factor
  • Article: Measurement of ER and PR status in breast cancer using the QuantiGene2.0 assay.
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    ABSTRACT: The QuantiGene2.0 assay has low interlaboratory variability and can directly measure RNA levels without a reverse transcription step or a polymerase chain reaction process. To evaluate the utility of the QuantiGene2.0 assay for the assessment of oestrogen receptor (ER) and progesterone receptor (PR) status as an alternative to immunohistochemistry (IHC), we compared disease-free survival according to quantitative ER and PR measurements when using IHC and the QuantiGene2.0 assay. Samples were collected from 171 patients who underwent breast cancer surgery between January 2003 and December 2006. Cox proportional hazard analysis was performed and concordance between IHC and the QuantiGene2.0 assay for the assessment of ER and PR status was evaluated. ER and PR assessments were well correlated between IHC and the QuantiGene2.0 assay. The difference in disease-free survival was statistically significant according to expression of PR, but not ER, between the two groups. The QuantiGene2.0 assay showed results similar to those of IHC for the assessment of ER and PR in response to treatment. Therefore, our data suggest that the QuantiGene2.0 assay can be used to determine ER and PR status and corroborate IHC findings, which at present are considered as the standard for the evaluation of ER and PR status.
    Pathology 04/2011; 43(3):248-53. · 2.38 Impact Factor
  • Article: Expression of nuclear receptor DAX-1 and androgen receptor in human breast cancer.
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    ABSTRACT: The functions of nuclear receptor DAX-1 and androgen receptor (AR) in breast cancer are unknown and have not been well-characterized in terms of their importance as a predictive or a prognostic factor. The study investigated the relationship between expression of AR, DAX-1, and clinicopathological factors in primary breast cancer patients. The data of 476 breast cancer patients who were treated at Seoul St. Mary's hospital from January 2004 to March 2006 were reviewed. Among them, 169 cases (35.5%) were consecutively evaluated for AR and DAX-1 expression. DAX-1 expression was associated with smaller tumor size; earlier disease stage; and higher expression of estrogen receptor (ER), progesterone receptor (PgR) and AR. AR was significantly expressed in patients with smaller tumor size and higher expression of ER, PgR, and DAX-1. In the subgroup analysis of triple negative breast cancer patients, the expression rate of DAX-1 (4/12, 33.3%) was higher than AR (1/12, 8.3%). The present review revealed a very high expression rate of DAX-1 in human breast cancer (74%). DAX-1 might modify steroidogenic hormone systems like as AR, estrogen receptor, and progesterone receptor. DAX-1 might be a more effective target than AR for triple negative breast cancer.
    Journal of Surgical Oncology 01/2011; 103(8):768-72. · 2.10 Impact Factor
  • Article: Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma.
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    ABSTRACT: Although many attempts have been made to predict the occurrence of lymph node metastases from papillary thyroid carcinoma, there are currently no reliable means to accurately predict cervical nodal metastasis. In this study, we present a novel prediction system for the lymph node metastasis based on the histological and cyclin D1 staining features. The frequency of lymph node metastases from a series of 210 papillary thyroid carcinomas was analyzed according to the clinicopathological variables, cyclin D1 staining patterns and BRAF(V600E) mutation in tumor tissue. A total of 113 (54%) patients had lymph node metastasis. Cyclin D1 was constantly expressed at the invasive tumor front and revealed well-defined isolated glands of tumor cells in the extra-tumoral region (isolated glands) and laterally spreading tubular growth along the fibrous septa around the invasive front of the tumor (lateral tubular growth). Upon univariate analysis, an age of less than 45 years (P<0.001), tumor size of 10 mm or more (P<0.001), non-follicular variant (P=0.005), invasive growth pattern (P=0.007), extrathyroid extension (P=0.006), isolated glands (P<0.001), lateral tubular growth (P<0.001) and tumor multiplicity (P=0.005) predicted lymph node metastasis, whereas BRAF(V600E) mutation did not. Upon multivariate analysis, age (P=0.001, odds ratio (OR)=5.146), tumor size (P=0.034, OR=3.119), isolated glands (P<0.001, OR=21.042) and lateral tubular growth (P<0.001, OR=24.652) were found to be strong independent predictors of lymph node metastasis. Cyclin D1 staining of papillary thyroid carcinoma is very useful for identifying the intrathyroidal spreading or multifocality of the tumors. Tumor growth patterns verified by cyclin D1 staining can be used for the identification of papillary thyroid carcinomas with metastatic potential.
    Modern Pathology 09/2010; 23(9):1201-8. · 4.79 Impact Factor
  • Article: Bilateral primary breast lymphoma.
    Chinese medical journal 06/2010; 123(11):1482-4. · 0.86 Impact Factor
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    Article: Genomic alterations of primary tumor and blood in invasive ductal carcinoma of breast.
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    ABSTRACT: Genomic alterations are important events in the origin and progression of various cancers, with DNA copy number changes associated with progression and treatment response in cancer. Array CGH is potentially useful in the identification of genomic alterations from primary tumor and blood in breast cancer patients. The aim of our study was to compare differences of DNA copy number changes in blood and tumor tissue in breast cancer. DNA copy number changes in blood were compared to those in tumor tissue using array-comparative genomic hybridization in samples obtained from 30 breast cancer patients. The relative degree of chromosomal changes was analyzed using log2 ratios and data was validated by real-time polymerase chain reaction. Forty-six regions of gains present in more than 30% of the tissues and 70 regions of gains present in more than 30% of blood were identified. The most frequently gained region was chromosome 8q24. In total, agreement of DNA copy numbers between primary tumor and blood was minimal (Kappa = 0.138, p < 0.001). Although there was only a slight agreement of DNA copy number alterations between the primary tumor and the blood samples, the blood cell copy number variation may have some clinical significance as compared to the primary tumor in IDC breast cancer patients.
    World Journal of Surgical Oncology 01/2010; 8:32. · 1.12 Impact Factor