Hyun Jin Son

NDRG2 expression decreases with tumor stages and regulates TCF/β-catenin signaling in human colon carcinoma

NDRG (N-Myc downstream-regulated gene)-2 is a member of the NDRG family. Although it has been suggested that NDRG2 is involved in cellular differentiation and tumor suppression, its intracellular signal and regulatory mechanism are not well known. Here, we show the differential expression of NDRG2 in human colon carcinoma cell lines and tissues by reverse transcription–polymerase chain reaction and immunohistochemical analyses with monoclonal antibody against NDRG2. NDRG2 was strongly expressed in normal colonic mucosa and colonic adenomatous tissues (25 of 25) but not in all invasive cancer tissues [44 of 99 (44%)]. Most distinctive results indicated that the high expression level of NDRG2 has a positive correlation with tumor differentiation and inverse correlation with tumor invasion depth and Dukes’ stage of colon adenocarcinoma. To investigate the roles of NDRG2 in tumorigenesis, we used in vitro cell culture system. SW620 colon cancer cell line with a low level of intrinsic NDRG2 protein was transfected with NDRG2-expressing plasmid. TOPflash luciferase reporter assay showed that the transcriptional activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) was reduced by NDRG2 introduction, but not by the introduction of mutant NDRG2 generated by deletion or site-directed mutagenesis. Intracellular β-catenin levels were slightly reduced in the NDRG2-transfected SW620 cells and this regulation of β-catenin stability and TCF/LEF activity were mediated through the modulation of glycogen synthase kinase-3beta activity by NDRG2 function. Our results suggest that NDRG2 might play a pivotal role as a potent tumor suppressor by the attenuation of TCF/β-catenin signaling for the maintenance of healthy colon tissues.

Primary Extrauterine Endometrial Stromal Sarcoma in the Sigmoid Colon

An endometrial stromal sarcoma (ESS) is an uncommon uterine neoplasm, and its primary occurrence in the intestine as an extrauterine ESS (EESS) is exceedingly rare. We hereby report a primary EESS arising in the sigmoid colon with a review of the literature. A 52-year-old woman presented with bloody stool and underwent a colon fiberscopy, which revealed a fungating mass obstructing the lumen at the distal sigmoid. A laparoscopic low anterior resection was performed, and an umbilicated polypoid mass was identified; on section, it had infiltrated the mesocolic fat and measured 3.8 cm × 2.5 cm. The tumor showed geographic sheets or nests composed of relatively monotonous stromal cells, expansion or infiltration to the proper muscle and mesocolic fat, and extensive lymphovascular invasion and metastasis to regional lymph nodes and the pelvic peritoneum. The tumor cells were strongly and diffusely immunoreactive for CD10, but negative for c-kit, CD34, and Dog1. Two months later, a hysterectomy with a bilateral salpingo-oophorectomy was performed, and no evidence of an ESS was found in the uterus.

A Case of Paratesticular Leiomyosarcoma Successfully Treated with Orchiectomy and Chemotherapy

A 50-year-old male patient presented with a right scrotal mass that had been growing rapidly for more than one year. A heterogeneous enhancing right scrotal mass (12×9 cm) with para-aortic and peri-caval lymphadenopathies was found on abdominal computed tomography (CT). Right orchiectomy was performed and the gross finding had shown intact testis with a well-defined, huge, whitish solid mass adjacent to the testis. According to pathology, the mass was characterized as a leiomyosarcoma, grade 3 (by National Cancer Instituted [NCI] system). Therefore, the diagnosis was stage III, grade 3 paratesticular leiomyosarcoma. The patient underwent additional systemic chemotherapy using ifosfamide and adriamycin. After nine cycles of chemotherapy, positron emission tomography-CT was performed and no FDP uptake was observed. The patient has been followed up for 12 months after systemic chemotherapy, and he has maintained a complete response. We report here on a rare case of paratesticular leiomyosarcoma treated successfully with orichiectomy and additional systemic chemotherapy.

Small Cell Carcinoma of the Gallbladder:

The diagnostic role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) for gallbladder small cell carcinoma has not been reported. A knowledge of the imaging characteristic features of this malignancy can be useful. Here we report a rare case of a patient who had various diagnostic imaging modalities, including 18F-FDG PET/CT.

^{18}F

Background Thymosin β4 is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinicopathologic implications of thymosin β4 expression in human colorectal cancers (CRCs). Methods We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β4 expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series. Results High expression of thymosin β4 was significantly correlated with lymphovascular invasion, invasion depth, regional lymph node metastasis, distant metastasis, and TNM stage. Patients with high expression of thymosin β4 showed poor recurrence-free survival (p = .001) and poor overall survival (p = .005) on multivariate analysis. We also found that thymosin β4 and HIF-1α were overexpressed and that thymosin β4 expression increased in parallel with HIF-1α expression in CRC. Conclusions A high expression level of thymosin β4 indicates poor clinical outcomes and may be a useful prognostic factor in CRC. Thymosin β4 is functionally related with HIF-1α and may be a potentially valuable biomarker and possible therapeutic target for CRC.

-FDG PET/CT Imaging Features-A Case Report

Hepatic perivascular epithelioid cell tumors (PEComas) are very rare. We report a primary hepatic PEComa with a review of the literature. A 56-year-old women presented with a nodular mass detected during the management of chronic renal failure and chronic hepatitis C. Diagnostic imaging studies suggested a nodular hepatocellular carcinoma in segment 5 of the liver. The patient underwent partial hepatectomy. A brown-colored expansile mass measuring 3.2×3.0 cm was relatively demarcated from the surrounding liver parenchyma. The tumor was mainly composed of epithelioid cells that were arranged in a trabecular growth pattern. Adipose tissue and thick-walled blood vessels were minimally identified. A small amount of extramedullary hematopoiesis was observed in the sinusoidal spaces between tumor cells. Tumor cells were diffusely immunoreactive for human melanoma black 45 (HMB45) and Melan A, focally immunoreactive for smooth muscle actin, but not for hepatocyte specific antigen (HSA).

Increased Expression of Thymosin β4 Is Independently Correlated with Hypoxia Inducible Factor-1α (HIF-1α) and Worse Clinical Outcome in Human Colorectal Cancer

Background There is subjective disagreement regarding nuclear clearing in papillary thyroid carcinoma. In this study, using digital instruments, we were able to quantify many ambiguous pathologic features and use numeric data to express our findings. Methods We examined 30 papillary thyroid carcinomas. For each case, we selected representative cancer cells showing clear nuclei and surrounding non-neoplastic follicular epithelial cells and evaluated objective values of green light intensity (GLI) for quantitative analysis of nuclear clearing in papillary thyroid carcinoma. Results From 16,274 GLI values from 600 cancer cell nuclei and 13,752 GLI values from 596 non-neoplastic follicular epithelial nuclei, we found a high correlation of 94.9% between GLI and clear nuclei. GLI between the cancer group showing clear nuclei and non-neoplastic follicular epithelia was statistically significant. The overall average level of GLI in the cancer group was over two times higher than the non-neoplastic group despite a wide range of GLI. On a polygonal line graph, there was a fluctuating unique difference between both the cancer and non-neoplastic groups in each patient, which was comparable to the microscopic findings. Conclusions Nuclear GLI could be a useful factor for discriminating between carcinoma cells showing clear nuclei and non-neoplastic follicular epithelia in papillary thyroid carcinoma.