Prevalence of Mutations in Discoidin Domain-Containing Receptor Tyrosine Kinase 2 (DDR2) in Squamous Cell Lung Cancers in Korean Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The discoidin domain-containing receptor tyrosine kinase 2 (DDR2) is known to contain mutations in a small subset of patients with squamous cell carcinomas (SCC) of the lung. Studying the DDR2 mutations in patients with SCC of the lung would advance our understanding and guide the development of therapeutic strategies against lung cancer. MATERIALS AND METHODS: We selected 100 samples through a preliminary genetic screen, including specimens from biopsies and surgical resection, and confirmed SCC by histologic examination. DDR2 mutations on exons 6, 15, 16, and 18 were analyzed by Sanger sequencing of formalin-fixed, paraffin-embedded tissue samples. The functional effects of novel DDR2 mutants were confirmed by in vitro assays. RESULTS: We identified novel somatic mutations of DDR2 in two of the 100 SCC samples studied. One mutation was c.1745T>A (p.V582E) and the other was c.1784T>C (p.L595P), and both were on exon 15. Both patients were smokers and EGFR/KRAS/ALK-triple negative. The expression of the mutant DDR2 induced activation of DDR2 by the collagen ligand and caused enhanced cell growth and tumor progression. Moreover, dasatinib, a DDR2 inhibitor, showed potential efficacy against DDR2 L595P mutant–bearing cells. CONCLUSION: Our results suggest that a mutation in DDR2 occurs naturally with a frequency of about 2% in Korean lung SCC patients. In addition, we showed that each of the novel DDR2 mutations were located in a kinase domain and induced an increase in cell proliferation rate.

Hepatic Lymphoma Representing Iso-Signal Intensity on Hepatobiliary Phase, in Gd-EOB-DTPA-Enhanced MRI: Case Report

Image findings of hepatic lymphoma have been reported as variable, ranging from single or multiple small nodules to diffuse infiltrative patterns. On MRI, most hepatic lymphomas show T1 low signal intensity, T2 high signal intensity. Dynamic imaging reveals a hypointense appearance in the arterial phase, followed by delayed enhancement in the portal venous and transitional phase. In the hepatobiliary phase using a hepatocyte-specific contrast agent (which have recently aided in increasing the access to the focal liver lesions), hepatic lymphoma is known to exhibit low signal intensity. We report a case of hepatic lymphoma, which shows iso-signal intensity on hepatobiliary phase, using gadoxetic acid (Gd-EOB-DTPA).

Coexistence of Intrapulmonary Bronchogenic Cyst and Congenital Cystic Adenomatoid Malformation: A Case Report

Congenital cystic lesions of the lung are uncommon and a conjunction of two or more lesions is very rare. We report here on a case of coexisting intrapulmonary bronchogenic cyst and congenital cystic adenomatoid malformation in a 13-year-old female with a cystic mass in the right upper lobe of the lung. Computed tomography showed a cystic lesion measuring 2.5 cm with an air fluid level and surrounding multicystic lesions in the right upper lobe. On gross examination, the cut surface showed a cystic mass containing inspissated mucinous material, and the cystic mass was surrounded by multiple small cysts. Microscopically, the larger cystic cavity was lined with pseudostratified ciliated columnar epithelium. The submucosal tissue contained mucinous glands and plates of cartilage. The surrounding smaller cysts or irregular spaces were lined with bronchiolar-type respiratory epithelium. We propose that this hybrid lung lesion may represent the missing link in a common embryologic pathway determined by the timing of mesenchymal and epithelial interactions.

Spindle Cell Epithelioma, a So-called Benign Mixed Tumor of the Vagina: A Case Report

We report a case of spindle cell epithelioma, a so-called benign mixed tumor of the vagina. The patient was a 35-year-old nulliparous woman who presented with a polypoid mass in the posterior wall of the lower vagina just above the hymenal ring. The tumor was relatively well-defined with an expansile margin and composed of stromal-type spindle cells with a myxoid stroma arranged in short fascicles and an irregular cord-like or reticular pattern. A few glandular structures lined by cuboidal cells with squamous metaplasia were also noted. Cellular atypia was not conspicuous and mitosis was not found. We examined this tumor immunohistochemically to identify the histogenesis. The coexpression of epithelial and mesenchymal markers in stromal-type spindle cells suggested a multipotential cell origin for this tumor. The patient has been well with no signs of recurrence during the 12 months after surgery.

Clinicopathological Significance of S100A4 Expression in Non-small Cell Lung Carcinomas

BACKGROUND: S100A4 has been implicated in invasion and metastasis of various malignant tumors. The aim of this study was to investigate whether or not S100A4 plays an important role in non-small cell lung carcinomas (NSCLCs). METHODS: Sixty-seven patients with NSCLC including 37 with squamous cell carcinomas (SCCs) and 30 with adenocarcinomas (ADs) who had undergone surgical resection were analyzed. S100A4 expression was analyzed by immunohistochemistry using tissue microarray blocks. RESULTS: S100A4 expression was positive in 56 (83.6%) of 67 NSCLC cases. ADs were more frequently S100A4 positive than SCCs (p = 0.017). However, no significant correlation was observed between S100A4 expression and age, gender, pT, pN or tumor, node and metastasis (TNM) stage. Two distant metastatic cases revealed an S100A4 positive reaction. Kaplan-Meier survival curves with the log-rank test showed no correlation with 3-year survival (p = 0.782) or 5-year survival (p = 0.227) in either group of patients according to S100A4 expression. CONCLUSIONS: S100A4 expression was not correlated with age, gender, pT, pN or TNM stage or survival in patients with NSCLCs. Therefore, S100A4 expression may not be useful as a prognostic marker for NSCLCs. However, S100A4 expression showed a higher positivity in ADs than in SCCs.

Calcifying Aponeurotic Fibroma of the Elbow: A Case Report

Calcifying aponeurotic fibroma is a rare soft tissue tumor that mostly occurs in the distal extremities of children and adolescents. We report here on a case of calcifying aponeurotic fibroma of the right elbow in an 8-year-old boy, and the tumor was diagnosed by surgical excision. The patient complained of painless swelling and mild limitation of the range of motion of the elbow joint. Radiologically, the mass was ill-defined and showed stippled calcification with shallow bony erosion. Microscopically, the tumor was composed of spindle cells with nodular deposits of hyalination and calcification, and these deposits were surrounded by palisading polygonal plump cells. Immunohistochemically, the tumor showed a diffuse positive expression for CD99 and negativity for smooth muscle actin, S-100 protein and CD34. The patient has been well with no signs of recurrence during the 42 months after surgery.

Characteristics of gene transfer and VEGF expression using naked plasmid vectors in the rat heart / 대한내과학회지

BACKGROUND: The purpose of this study was to compare gene expression among newly designed eukaryotic expression vectors, and to characterize the pattern of vascular endothelial growth factor(VEGF) expression using the most potent plasmids DNA vector. METHODS: After exposure of a beating rat heart (Sprague-Dawley, 250-300g), 5 different types of plasmid DNA was injected directly into the myocardium. Reporter protein was analyzed by ELISA in the extracted heart. RESULTS: The vector harboring cytomegalovirus (CMV) promoter and enhancer induced the strongest expression of reporter gene (chloramphenicol acetyl transferase; CAT) compared to those of pC3.1, pEF1a, RSV, pActin in the rat heart via direct injection of plasmid DNA into the apex (p<0.001). Using pCN-CAT, gene expression showed a dose-dependent response over a range of 0.3-10 (mu)g. CAT expression could be detected up to 30 days after 10 (mu)g of pCN-CAT injection with the maximal expression on day 5. In X-gal staining of injected pCN-lacZ gene, beta-galactosidase was found only around the needle track in the apex. The expressed hVEGF121 had biologic activity with vascular permeability assay (Miles assay) in guinea pigs. After injection of pCN-hVEGF121 into the apex of the rat heart, the expression of VEGF protein was dose-dependent over the range of 25 and 500 (mu)g. VEGF expression was detected up to 14 days with its peak on day 2 after injection of 250 (mu)g of pCN-hVEGF121. When plasmid was injected into the apex of the rat heart, the expression of VEGF in the heart showed concentration gradient from the apex to the base. However, the expression of CAT was detected only in the apex. CONCLUSION: Plasmids vector with hCMV IE promoter/enhancer will provide clear advantages over other previously developed plasmids and the information regarding the behaviors of VEGF expression may be useful in angiogenic gene therapy of the heart.