Young Bum Yoo

Surgical Results of Thyroid Nodules according to a Management Guideline Based on the BRAFV600E Mutation Status

CONTEXT In Korea, where PTC comprises about 90-95% of the reported thyroid cancers, the prevalence of BRAF(V600E) mutation in papillary thyroid carcinoma (PTC) is above 80%. OBJECTIVE We analyzed the surgical result according to a management guideline based on the BRAF(V600E) mutation status of thyroid nodules. DESIGN A total of 865 thyroid nodules were prospectively analyzed for their cytology and BRAF(V600E) mutation status by pyrosequencing. For the patients who had a diagnosis of atypical cells of undetermined significance (ACUS), we recommended surgery when there was positivity for BRAF(V600E) mutation or the nodules were clinically suspicious. RESULTS Among 865 cases, 504, 141, 54, 140, 10, and 16 were diagnosed as benign, ACUS, suspicious for malignancy, malignant, suspicious for follicular neoplasm, and nondiagnostic, respectively. None of the 504 benign, 45 (31.9%) of the 141 ACUS, 46 (85.2%) of the 54 suspicious for malignancy, 129 (92.1%) of the 140 malignant, and one (10%) of the 10 suspicious for follicular neoplasm cases showed BRAF(V600E) mutation. Surgery was recommended to all 45 patients with BRAF(V600E) mutation-positive ACUS nodules; among them, 30 patients underwent surgery, 29 had PTC, and one had nodular hyperplasia. All the patients diagnosed as suspicious for malignancy or malignant were advised to undergo an operation, and they turned out to have PTCs regardless of their BRAF(V600E) mutation status. CONCLUSIONS We found that performing BRAF(V600E) mutation analysis on the fine-needle aspiration biopsy specimens was of great help to make a therapeutic decision for thyroid nodules when the fine-needle aspiration biopsy results were equivocal.

Clinical and Pathological Features and the BRAFV600E Mutation in Patients with Papillary Thyroid Carcinoma with and without Concurrent Hashimoto Thyroiditis

BACKGROUND It has been reported that patients with papillary thyroid carcinoma (PTC) have a high incidence of background Hashimoto thyroiditis (HT); however, the linkage of HT to PTC is controversial. Recent studies have shown that the prevalence of activating point mutations in BRAFV600E is much higher (73-86%) in Korea than in Western countries (29-69%), and associated with a poor prognosis in PTC. The purpose of the present study was to investigate the frequency of the BRAFV600E mutation in PTC with and without HT, and to determine clinical and pathological features that were associated with concomitant HT and PTC. METHODS Fine-needle aspiration slides from 101 patients with surgically confirmed PTC were studied. The DNA was extracted from the atypical cells that were scraped from slides. It was then analyzed for the BRAFV600E mutation by pyrosequencing. In addition, the presence of background HT in surgical specimens and other clinical and pathological features of the patients were characterized. RESULTS HT was present in 37 (36.6%) of the patients. The BRAFV600E mutation was present in 27 (72.9%) of patients with HT but was present in 61 (95.3%) of patients without HT ( p#0.01). The inverse correlation of concurrent HT with the BRAFV600E mutation was significant for both males and females ( p < 0.01). The presence of background HT was not associated with tumor size, extrathyroidal invasion, lymph node (LN) metastasis, or tumor stage. The patients were younger in the group without background HT (44.1 +/- 13.2 vs. 49.8 +/- 13.9, p 1/40.05). The BRAFV600E mutation was present in 88 (87.1%) of the 101 patients with PTC. The presence of the BRAFV600E mutation was significantly associated with LN metastasis ( p < 0.02; odds ratio, 6.24; 95% confidence interval, 1.51-25.79). CONCLUSION In Korean patients with PTC, the BRAFV600E mutation is associated with a lower frequency of background HT and a high frequency of LN metastasis.

Effects of combination therapy of docetaxel with selenium on the human breast cancer cell lines MDA-MB-231 and MCF-7

Purpose The anticancer property and cytoprotective role of selenium in chemotherapy have been reported. However, the combination effects of selenium on chemotherapy for advanced breast cancer have not yet been clearly defined. The purpose of this study was to investigate the combined effects of selenium on chemotherapy using docetaxel on breast cancer cell lines. Methods Under adherent culture conditions, two breast cancer cell lines, MDA-MB-231 and MCF-7, were treated with docetaxel at 500pM and selenium at 100nM, 1µM, or 10µM. Changes in cell growth, cell cycle duration, and degree of apoptosis after 72 hours in each treated group were evaluated. Results In the MDA-MB-231 cells, the combination therapy group (docetaxel at 500pM plus selenium at 10µM) showed a significantly decreased percentage of cell growth (15% vs. 28%; P = 0.004), a significantly increased percentage of late apoptosis (63% vs. 26%; P = 0.001), and an increased cell cycle arrest in the G2/M phase (P = 0.001) compared with the solitary docetaxel therapy group. Isobologram analysis demonstrated the synergistic effect of the combination therapy in the MDA-MB-231 cells. However, in the MCF-7 cells, no significant differences in the percentage of cell growth apoptosis, the percentage of apoptosis, and the pattern of cell cycle arrest were noted between the combination therapy groups and the solitary docetaxel therapy group. Conclusion Our in vitro study indicated that the combination of selenium with docetaxel inhibits cell proliferation through apoptosis and cell arrest in the G2/M phase in MDA-MB-231 breast cancer cells.

RAS mutations in indeterminate thyroid nodules are predictive of the follicular variant of papillary thyroid carcinoma.

RAS mutations are the most common mutations in thyroid nodules with indeterminate cytology by fine‐needle aspiration cytology (FNAC), and are mutually exclusive with BRAF mutations. However, the diagnostic utility of RAS mutation analysis is uncertain. We evaluated the diagnostic utility of RAS mutation analysis in indeterminate thyroid nodules.

Axillary sparganosis which was misunderstood lymph node metastasis during neoadjuvant chemotheraphy in a breast cancer patient

Sparganosis of the breast is an uncommon disease, but should be considered in the differential diagnosis of unusual and suspicious breast masses. A history of ingesting contaminated water and direct ingestion of snakes and frogs may help in differential diagnosis of the mass. Complete surgical removal is the treatment of choice and provides a definite diagnosis. We report a case of multiple axillary lymph node sparganosis. It was first considered as an axillary metastasis of breast cancer because a newly axillary mass appeared in follow-up radiologic study after neoadjuvant chemotherapy. We performed curative breast cancer surgery and sparganosis was confirmed by extracting the worm during axillary dissection.

Imaging mass spectrometry in papillary thyroid carcinoma for the identification and validation of biomarker proteins.

Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization and time-of-flight (MALDI-TOF) mass spectrometry has become increasingly important in biology and medicine, because this technology can detect the relative abundance and spatial distribution of interesting proteins in tissues. Five thyroid cancer samples, along with normal tissue, were sliced and transferred onto conductive glass slides. After laser scanning by MALDI-TOF equipped with a smart beam laser, images were created for individual masses and proteins were classified at 200-µm spatial resolution. Based on the spatial distribution, region-specific proteins on a tumor lesion could be identified by protein extraction from tumor tissue and analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using all the spectral data at each spot, various intensities of a specific peak were detected in the tumor and normal regions of the thyroid. Differences in the molecular weights of expressed proteins between tumor and normal regions were analyzed using unsupervised and supervised clustering. To verify the presence of discovered proteins through IMS, we identified ribosomal protein P2, which is specific for cancer. We have demonstrated the feasibility of IMS as a useful tool for the analysis of tissue sections, and identified the tumor-specific protein ribosomal protein P2. Graphical Abstract

Preoperative RAS Mutational Analysis Is of Great Value in Predicting Follicular Variant of Papillary Thyroid Carcinoma

Follicular variant of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6%) had a point mutation in one of the BRAF V600E (n = 57), BRAF K601E (n = 11), or RAS (n = 64) genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.

False positive or negative results of shear-wave elastography in differentiating benign from malignant breast masses: analysis of clinical and ultrasonographic characteristics

Background Shear-wave elastography (SWE) has the potential to improve diagnostic performance of conventional ultrasound (US) in differentiating benign from malignant breast masses. Purpose To investigate false positive or negative results of SWE in differentiating benign from malignant breast masses and to analyze clinical and imaging characteristics of the masses with false SWE findings. Material and Methods From May to October 2013, 166 breast lesions of 164 consecutive women (mean age, 45.3 ± 10.1 years) who had been scheduled for biopsy were included. Conventional US and SWE were performed in all women before biopsy. Clinical, ultrasonographic morphologic features and SWE parameters (pattern classification and standard deviation [SD]) were recorded and compared with the histopathology results. Patient and lesion factors in the “true” and “false” groups were compared. Results Of the 166 masses, 118 (71.1%) were benign and 48 (28.9%) were malignant. False SWE features were more frequently observed in benign masses. False positive rates of benign masses and false negative rates of malignancy were 53% and 8.2%, respectively, using SWE pattern analysis and were 22.4% and 10.3%, respectively, using SD values. A lesion boundary of the masses on US (P = 0.039) and younger patient age (P = 0.047) were significantly associated with false SWE findings. Conclusion These clinical and ultrasonographic features need to be carefully evaluated in performance and interpretation of SWE examinations.

Complementary Role of Semiquantitative Analysis of Breast-Specific Gamma Imaging in the Diagnosis of Breast Cancer

OBJECTIVE We investigated whether the interpretation of breast-specific gamma imaging (BSGI) with visual and semiquantitative analyses can improve the diagnosis of breast cancer. MATERIALS AND METHODS The records of 114 women (mean age±SD, 49.6±9.8 years) who underwent BSGI, mammography, and ultrasound to evaluate a breast lesion or lesions were reviewed retrospectively. The breast lesions identified with BSGI were compared with those identified with mammography and ultrasound. BSGI was first interpreted visually, and then a semiquantitative analysis was performed. For the semiquantitative analysis, the uptake ratio for each breast lesion was calculated by dividing the tumor uptake by the contralateral normal breast uptake. RESULTS Four of the 114 patients had two breast lesions, so a total of 118 breast lesions (42 malignant lesions and 76 benign lesions) were evaluated. A BSGI uptake ratio cutoff of 1.5, with values less than 1.5 indicating negative for cancer, as determined by receiver operating characteristic curve analysis of our data (area under curve, 0.874), was used for semi-quantitative analysis. The sensitivity and specificity of BSGI with visual analysis alone for assessing malignant breast lesions were 76.2% (32/42) and 81.6% (62/76), respectively. For BSGI with visual and semiquantitative analyses, the sensitivity and specificity were 76.2% (32/42) and 92.1% (70/76), respectively. The sensitivity and specificity for mammography were 57.1% (24/42) and 81.6% (62/76), respectively. For ultrasound, the respective values were 97.6% (41/42) and 61.8% (47/76). BSGI with visual and semiquantitative analyses had a significantly higher specificity than BSGI with visual analysis alone, mammography, and ultrasound (all, p<0.01). CONCLUSION Semiquantitative analysis of BSGI with visual interpretation may be a useful complementary method for evaluating malignant breast lesions.

A comparative analysis of endoscopic thyroidectomy versus conventional thyroidectomy in clinically lymph node negative thyroid cancer

Purpose Differentiated thyroid cancer has a good prognosis and high incidence in young women. Since endoscopic techniques were first recorded in 1996, surgical indications of endoscopic thyroidectomy have broadened. Therefore, the aim of this study is to investigate the usefulness of endoscopic thyroidectomy in clinically lymph node negative (cN0) thyroid cancer patients, based on oncologic completeness and safety, considering cosmetic outcomes. Methods From July 2009 to June 2011, a total of 166 cases had undergone endoscopic thyroidectomy using the BABA (bilateral axillo-breast approach) method or conventional open thyroidectomy by one surgeon. Finally, excluding 72 patients, 94 patients with cN0 thyroid cancer were divided into two groups according to operative methods and analyzed to compare differences between the two methods retrospectively (endoscopic group, n = 49; conventional open group, n = 45). Results We practiced comparative analysis for clinicopathologic characteristics, surgical outcomes including postoperative complications, and recurred cases during follow-up periods of each group. The results showed there was a tendency for patients, young, women rather than men, and having small size of thyroid cancer, to prefer endoscopic surgery to open surgery. Meanwhile, in postoperative complications, there were no statistically significant differences. During short follow-up periods, no recurrence or mortality case was observed. Conclusion Endoscopic thyroidectomy is a feasible and safe method for the treatment of clinically lymph node negative (cN0) thyroid cancer.