The Use of the Bethesda System for Reporting Thyroid Cytopathology in Korea: A Nationwide Multicenter Survey by the Korean Society of Endocrine Pathologists.

BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) has standardized the reporting of thyroid cytology specimens. The objective of the current study was to evaluate the nationwide usage of TBSRTC and assess the malignancy rates in each category of TBSRTC in Korea. METHODS: Questionnaire surveys were used for data collection on the fine needle aspiration (FNA) of thyroid nodules at 74 institutes in 2012. The incidences and follow-up malignancy rates of each category diagnosed from January to December, 2011, in each institute were also collected and analyzed. RESULTS: Sixty out of 74 institutes answering the surveys reported the results of thyroid FNA in accordance with TBSRTC. The average malignancy rates for resected cases in 15 institutes were as follows: nondiagnostic, 45.6%; benign, 16.5%; atypical of undetermined significance, 68.8%; suspicious for follicular neoplasm (SFN), 30.2%; suspicious for malignancy, 97.5%; malignancy, 99.7%. CONCLUSIONS: More than 80% of Korean institutes were using TBSRTC as of 2012. All malignancy rates other than the SFN and malignancy categories were higher than those reported by other countries. Therefore, the guidelines for treating patients with thyroid nodules in Korea should be revisited based on the malignancy rates reported in this study.

Nuclear EpICD expression and its role in hepatocellular carcinoma.

Regulated intramembrane proteolysis of epithelial cell adhesion molecule (EpCAM) results in shedding of the extracellular domain (EpEX) and release of the intra-cellular domain (EpICD) into the cytoplasm. Released EpICD associates with FHL2, ß-catenin and Lef-1 to form a nuclear complex and triggers oncogenic signaling. This study was conducted to examine the nuclear expression of EpICD in hepatocellular carcinoma (HCC) and to assess the role of EpICD in HCC. EpICD immunoexpression was examined in 100 cases of HCC using tissue microarrays and correlated with clinicopathological parameters. We also examined the role of EpICD in HCC using EpICD cDNA transfected HCC cell line and EpCAM silenced HCC cell line by small interfering RNA (siRNA). Nuclear expression of EpICD was observed in 19 of 100 (19%) cases. Nuclear expression of EpICD significantly correlated with nuclear expression of ß-catenin, and Ki-67 labeling index. In addition, nuclear expression of EpICD was associated with higher histologic grade and advanced T category. Forced overexpression of EpICD in the HCC cell significantly increased the cell proliferation, migration and invasion. The overexpression of EpICD also increased the expression levels of the active form of ß-catenin and c-myc and cyclin D1. In contrast, downregulation of EpCAM by siRNA decreased the cell proliferation, migration, invasion and the expression of active form of ß-catenin, c-myc and cyclin D1. Our present data suggest that EpICD plays important roles in HCC progression by modulating expression of target genes of EpCAM.

A quantum dot-based microfluidic multi-window platform for quantifying the biomarkers of breast cancer cells.

Conventional molecular profiling methods using immunochemical assays have limits in terms of multiplexity and the quantification of biomarkers in investigation of cancer cells. In this paper, we demonstrate a quantum dot (QD)-based microfluidic multiple biomarker quantification (QD-MMBQ) method that enables labeling of more than eight proteins immunochemically on cell blocks within 1 h, in a quantitative manner. An internal reference, ß-actin, was used as a loading control to compensate for differences in not only the cell number but also in staining quality among specimens. Furthermore, the microfluidic blocking method exhibited less nonspecific binding of QDs than the conventional static blocking method.

Epithelioid trophoblastic tumor presenting as an ovarian mass in a postmenopausal woman.

Epithelioid trophoblastic tumor (ETT) is a rare neoplasm derived from chorionic-type intermediate trophoblastic cells. Most cases of ETT are intrauterine and present during reproductive age. We report a case of ovarian ETT developing 47 yr after the patient's last pregnancy. A 75-yr-old woman transferred to our hospital because of multiple pulmonary masses which was diagnosed as sqaumous cell carcinoma in another hospital. PET-CT revealed a huge solid mass in the pelvic cavity, suspicious for ovarian malignancy. Serum ß-hCG was 57,971 mIU/mL. Hysterectomy and bilateral salpingo-oophorectomy were performed. Gross examination showed an enlarged right ovary, measuring 17×14×7 cm. The cut surface was yellow-tan and solid with extensive areas of necrosis. The uterus was unremarkable. The histologic finding was the same as the previous lung biopsy. The tumor consisted of monomorphic cells with abundant eosinophilic cytoplasm, forming solid sheets and nests. There was geographic tumor cell necrosis with hyaline materials. Immunohistochemically, cytokeratin 7 and p63 showed diffuse reactivity in the tumor cells. There was focal staining for ß-hCG. Ki-67 proliferative index was about 80%. This case indicates that ETT can rarely occur in postmenopausal women and to the best of our knowledge, our patient is the oldest reported case of ETT to date.

EZH2 expression in invasive lobular carcinoma of the breast.

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, but the prognosis of ILC is still controversial. Enhancer of Zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2 (PRC2), is frequently overexpressed in various cancers. This study evaluated the relationship between clinicopathologic characteristics and EZH2 expression. METHODS: We retrospectively reviewed the medical records of 54 patients with ILC and selected 49 cases of ILC. Immunohistochemistry for EZH2 was undertaken. RESULTS: We defined ILC as discohesive cells with a linear or nonlinear growth pattern. No statistically significant difference was found for most variables, including multifocality, menstrual status, body mass index, tumor stage (pT), lymph node stage (pN), estrogen receptor, and progesterone receptor. In contrast, nuclear grade was statistically significant and EZH2 expression was associated with high nuclear grade. In total, 80% of nuclear grade 3 cases had an EZH2 score of 4, and 86% of nuclear grade 1 cases had EZH2 scores of 1 and 2. Our cases had a score of 3 for tubule formation and a score of 1 for mitosis, and so the histologic grading consisted of grades 1 (7 cases) and 2 (42 cases) depending on the nuclear grade. CONCLUSION: Although EZH2 could not predict survival in our study, EZH2 expression was associated with a high nuclear grade. Most ILCs have histologic grade 2 with nuclear grade 2 or 3. Therefore, our opinion is that if ILC is diagnosed by separating the classic type and variants and considering both EZH2 expression and nuclear grade, EZH2 overexpression could help and the Nottingham grading system would be more accurate prognostic factor.

Colonic adenocarcinoma arising from gastric heterotopia: a case study.

Heterotopic gastric mucosa occurs in all areas of the gastrointestinal tract including the nasopharynx, tongue, esophagus, small intestine, colon, and rectum. Gastric heterotopia of the large bowel is infrequent, and most cases have been reported in the rectum. Review of the literature has revealed only eight cases involving the colon proximal to the rectum. Little is known of the natural history of gastric heterotopias, except that. It usually presents with gastrointestinal bleeding, though other serious complications such as bowel perforation, intussusceptions, and fistula formation, are possible. Further, it is unclear whether heterotopic gastric mucosa progresses to malignancy. Herein, we describe a case of adenocarcinoma of the transverse colon arising from gastric heterotopia. To the best of our knowledge, this is the first report of adenocarcinoma arising from heterotopic gastric mucosa in the colon.

Mesenteric pseudocyst of the small bowel in gastric cancer patient: a case report.

Mesenteric pseudocyst is rare. This term is used to describe the abdominal cystic mass, without the origin of abdominal organ. We presented a case of mesenteric pseudocyst of the small bowel in a 70-year-old man. Esophago-gastro-duodenoscopy showed a 3.5 cm sized excavated lesion on the posterior wall of angle. Endocopic biopsy confirmed a histologic diagnosis of the poorly differentiated adenocarcinoma, which includes the signet ring cell component. Abdominal computed tomography scan showed a focal mucosal enhancement in the posterior wall of angle of the stomach, a 2.4 cm sized enhancing mass on the distal small bowel loop, without distant metastases or ascites in rectal shelf, and multiple gallbladder stones. The patient underwent subtotal gastrectomy with gastroduodenostomy, segmental resection of the small bowel, and cholecystectomy. The final pathological diagnosis was mesenteric pseudocyst. This is the first case report describing incidentally detected mesenteric pseudocyst of the small bowel in gastric cancer patients.

Histone deacetylases 1, 6 and 8 are critical for invasion in breast cancer.

Histone deacetylases (HDACs) are associated with the development and progression of cancer, but it is not known which of the HDAC isoforms play important roles in breast cancer metastasis. This study identified the specific HDAC isoforms that are necessary for invasion and/or migration in human breast cancer cell lines. MDA-MB-231 cells were significantly more invasive and expressed higher levels of matrix metalloproteinase-9 (MMP-9) compared to MCF-7 cells. We compared the expression of HDAC isoforms between MCF-7 and MDA-MB-231 cells and found greater expression of HDAC4, 6 and 8 in MDA-MB-231 cells by RT-PCR and Western blot analyses. In addition, apicidin, a histone deacetylase inhibitor, was shown to attenuate the invasion, migration and MMP-9 expression in MDA-MB-231 cells. Using specific siRNAs directed against HDAC1, 4, 6 and 8, we show that inhibition of HDAC1, 6 and 8, but not HDAC4, are responsible for invasion and MMP-9 expression in MDA-MB-231 cells. We analyzed the invasiveness of MCF-7 cells overexpressing HDAC1, 4, 6 or 8 and found that overexpression of HDAC1, 6 or 8 increased invasion and MMP-9 expression. By developing HDAC isoforms as potential biomarkers for breast cancer metastasis, the present study can be extended to developing therapies for breast cancer invasion.

Lysophosphatidic acid induces STAT3 phosphorylation and ovarian cancer cell motility: their inhibition by curcumin.

Lysophosphatidic acid (LPA) is a biolipid that stimulates tumor cell invasion and metastasis. In this report, we determined the role of signal transducers and activators of transcription 3 (STAT3) and the effect of a chemopreventive agent, curcumin, on LPA-induced ovarian cancer cell motility. LPA phosphorylated STAT3 in a dose-dependent manner. Treatment of cells with a JAK/STAT inhibitor, AG490, inhibited LPA-induced cell motility. In contrast, transfection of a constitutively active form of STAT3 induced ovarian cancer cell motility. LPA also stimulated interleukin (IL)-6 and IL-8 secretion, which results in STAT3 phosphorylation. Treatment of the cells with curcumin inhibited LPA-induced IL-6 and IL-8 secretion and STAT3 phosphorylation, leading to blocked ovarian cancer cell motility. Collectively, the present study shows the critical role of STAT3 in ovarian cancer cell motility and that this process can be prevented by curcumin.