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Corneal dystrophy typically refers to a group of rare hereditary disorders with a heterogeneous genetic background. A comprehensive molecular genetic analysis was performed to characterize the genetic spectrum of corneal dystrophies in Korean patients. Patients with various corneal dystrophies underwent thorough ophthalmic examination, histopathologic examination, and Sanger sequencing. A total of 120 probands were included, with a mean age of 50 years (SD = 18 years) and 70% were female. A total of 26 mutations in five genes (14 clearly pathogenic and 12 likely pathogenic) were identified in 49 probands (41%). Epithelial-stromal TGFBI dystrophies, macular corneal dystrophy and Schnyder corneal dystrophy (SCD) showed 100% mutation detection rates, while endothelial corneal dystrophies showed lower detection rates of 3%. Twenty six non-duplicate mutations including eight novel mutations were identified and mutations associated with SCD were identified genetically for the first time in this population. This study provides a comprehensive characterization of the genetic aberrations in Korean patients and also highlights the diagnostic value of molecular genetic analysis in corneal dystrophies.

Background The purpose of this study was to determine the role of lymph node micrometastasis in oral and oropharyngeal cancers. Methods We investigated the presence of micrometastases by cytokeratin immunohistochemical staining in 54 patients with node-negative oral and oropharyngeal carcinomas. Results The positive rate of cytokeratin expression was 13.0% (7 of 54 patients). The incidence of micrometastasis was significantly higher in patients with more invasive tumors (p < .001) and larger tumor size (p = .034). The 5-year disease-specific (DS) survival rate significantly correlated with micrometastasis, margin involvement, and depth of invasion in the univariate analyses. Multivariate Cox regression analysis confirmed a significant association between the 5-year DS survival rate and micrometastasis (hazard ratio [HR] = 7.89; 95% confidence interval [CI] = 1.09–57.14; p = .041) and margin involvement (HR = 11.68; 95% CI = 1.22–111.75; p = .033). Conclusion Micrometastasis was significantly correlated with the depth of invasion and tumor size in oral and oropharyngeal cancers. Furthermore, micrometastasis was associated with adverse outcomes. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Meningiomas are slow-growing neoplasms that recur locally. Their morphologic grading does not always correlate with patient outcome. We evaluated the status of several immunohistochemical markers with histopathologic parameters in various grades of meningioma.Eighty-eight meningioma specimens were examined immunohistochemically to determine the status of Ki-67, cyclin D1, epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and bcl-2. Several clinical and pathological parameters were investigated.Forty-nine Grade I, 33 Grade II, and 6 Grade III meningiomas were observed. VEGF and Ki-67 expression was correlated with higher tumor grade. The association between grade and other immunohistochemical markers expression was not significant. A correlation was observed between COX-2 expression and invasiveness to the brain or adjacent soft tissue. Tumor recurrence was correlated with brain or adjacent soft tissue invasion. We also observed a relationship between VEGF level and COX-2 expression, and they were both correlated with necrosis.Immunohistochemical evaluation of VEGF, COX-2, and Ki-67 expression can provide information regarding the behavior of meningiomas, particularly for cases in which histological grading is not straightforward.

Obese women have an increased risk for post-menopausal breast cancer. The physiological mechanism by which obesity contributes to breast tumourigenesis is not understood. We previously showed that HCCR-1 oncogene contributes to breast tumourigenesis as a negative regulator of p53 and detection of HCCR-1 serological level was useful for the diagnosis of breast cancer(.) In this study, we found that the HCCR-1 level is elevated in breast cancer tissues and cell lines compared to normal breast tissues. We identified apolipoprotein E (ApoE) interacting with HCCR-1. Our data show that HCCR-1 inhibits anti-proliferative effect of ApoE, which was mediated by diminishing ApoE secretion of breast cancer cells. Finally, HCCR-1 induced the severe obesity in transgenic mice. Those obese mice showed severe hyperlipidaemia. In conclusion, our results suggest that HCCR-1 might play a role in the breast tumourigenesis while the overexpression of HCCR-1 induces the obesity probably by inhibiting the cholesterol-lowering effect of ApoE. Therefore, HCCR-1 seems to provide the molecular link between the obesity and the breast cancer risk.

Background and aim: The objective of this paper is to evaluate the workload of staff in anatomic pathology (AP) laboratories in Korea. Methods: A survey was conducted at 197 AP laboratories in South Korea, these were categorized as 37 free standing laboratories, 14 laboratories in non-training hospitals (without residents), 79 in training hospitals (with residents), and 67 in university hospitals. The workloads of the staff were analyzed using the mean and standard deviation of the number of cases. Results: In total, there were 512 pathologists, 806 technicians and 205 cytopathology screeners. In a year, they processed a total of 3,150,261 histopathology cases and 4,115,420 cytopathology cases. The numbers of histopathology cases per pathologist or technician in one laboratory were 6,950 ± 6,748 and 4,074 ± 3,630, respectively. There were 109 laboratories that employed 205 cytoscreeners in addition to the 308 pathologists, where a cytoscreener read 14,780 ± 13,110 cases of cytopathology. However, in 88 laboratories, there were 132 pathologists who were not assisted by cytoscreeners, where a pathologist was reading 4,277 ± 3,033 cases of cytopathology. Conclusion: We propose a mean plus a standard deviation as a recommended guideline for staff workload at each laboratory setting to be used for a quality assurance program.

We tried to investigate the expression rate of human papillomavirus (HPV) L1 capsid protein in uterine cervical specimens and correlate it with the grade of dysplasia, HPV genotype and age of the patients. Among uterine cervical specimens proved to have HPV by DNA genotyping test, eighty cytology-biopsy matched cases and 22 unmatched cytology specimens were selected. Immunostaining for L1 capsid protein was performed on both cervical smears and tissue sections. The L1 capsid protein was expressed mainly in the nuclei, but occasionally in the cytoplasm of cells located in the superficial layer of squamous epithelium. The immunostaining for L1 capsid protein showed positive reaction in 47 cases (46.1%) of cervical smears and in 10 cases (12.5%) of tissue sections (P = 0.001). Cytologic diagnosis revealed a higher expression rate in LSILs (25/33; 75.8%) than in HSILs and cervical cancers (8/20; 40.0% and 2/5; 40%, respectively) (P = 0.006). In LSILs, cases with low-risk type HPV showed a higher L1 capsid expression rate than those with the high-risk type HPV (88.9% vs. 70.8%). The L1 capsid expression rate decreased in the over-40-year-old age group compared to the younger age (49.2% vs. 50.8%). Cytology smears were superior to tissue sections for the detection of L1 capsid protein expression. LSILs and HPV low-risk group showed higher L1 capsid expression rate than HSILs and HPV high-risk group, which suggests that L1 capsid expression might be related to a favorable disease biology.

Aims: α-Fetoprotein (AFP) is frequently detected in hepatocellular carcinomas (HCCs) and AT motif binding factor 1 (ATBF1) down-regulates AFP gene expression in hepatic cells. The ATBF1 gene also inhibits cell growth and differentiation, and altered gene expression is associated with malignant transformation. The aim was to investigate the potential role of the ATBF1 gene in HCCs. Methods and results: Somatic mutations, allelic loss and hypermethylation of the ATBF1 gene were analysed in 76 sporadic HCCs. The level of ATBF-1 mRNA expression was analysed using quantitative real-time reverse transcriptase-polymerase chain reaction. Genetic studies of the ATBF1 gene revealed absence of somatic mutation in the hotspot region and 15 (25%) of 60 informative cases showed allelic loss at the ATBF1 locus. Hypermethylation in the intron 1 region of the ATBF1 gene was detected in only one case. Interestingly, ATBF1 mRNA expression in HCCs was significantly reduced in 55 (72.4%) samples compared with the corresponding surrounding liver tissues. Reduced expression was not statistically associated with clinicopathological parameters including stage, histological grade, infective virus type, and serum α-fetoprotein level. Conclusions: The ATBF1 gene may contribute to the development of HCCs via transcriptional down-regulation of mRNA expression, but not by genetic or epigenetic alterations.

Background and Aim: In hepatocarcinogenesis, both de novo and multistep pathways have been suggested, and in the latter a dysplastic nodule is the proposed precancerous lesion. But genetic changes involved in the dysplastic nodule are not well understood. In this study, we tried to determine whether allelic loss of the chromosome 8p and/or 11p could be involved in the development of the dysplastic nodule and/or hepatocellular carcinoma. Platelet-derived growth factor-receptor beta-like tumor suppressor gene (PRLTS) and deletion in liver cancer-1 tumor suppressor gene are located at 8p21.3-p22. The hepatitis B virus integration site and WT1 tumor suppressor gene are located at 11p13. Methods: We therefore studied loss of heterozygosity (LOH) of chromosome 8p21.3–p22 and 11p13 in 22 dysplastic nodules and 21 hepatocellular carcinomas. The samples, microdissected from paraffin-embedded tissues, were examined using a polymerase chain reaction-based LOH assay using microsatellite markers. Results: Loss of heterozygosity was detected for chromosome 8p21.3–p22 in nine (40.9%) of 22 dysplastic nodules and in eight (42.1%) of 19 hepatocellular carcinomas. D8S261, located adjacent to PRLTS, showed most frequent LOH: 28.6% in dysplastic nodule and 40.0% in hepatocellular carcinoma. Loss of heterozygosity on chromosome 11p13 was found in three (15.8%) of 19 dysplastic nodules and in six (31.6%) of 19 hepatocellular carcinomas. Loss of heterozygosity of D11S995 and D11S907 was found in 33.3% and 7.1% of dysplastic nodules, and 8.3% and 44.4% of hepatocellular carcinomas, respectively. Conclusion: These results suggest that at least one putative tumor suppressor gene involved in the development and progression of hepatocellular carcinoma may be located on 8p21.3–p22 and 11p13. Particularly, PRLTS might be related to an early genetic event of hepatocarcinogenesis. © 2003 Blackwell Publishing Asia Pty Ltd

Background. It is still a point of controversy whether Helicobacter pylori-infected patients are more likely to develop mucosal damage while taking NSADIs. Selective cyclooxygenase (COX-2) inhibitors may be associated with less severe gastric mucosal damage than conventional NSAIDs, but this association is undefined in H. pylori-induced gastritis. The aim of this study was to evaluate the effects of selective COX-2 and nonselective NSAIDs on H. pylori-induced gastritis. Methods. After intragastric administration of indomethacin, NS-398 or vehicle alone, once daily for 5 days in H. pylori-infected and uninfected Mongolian gerbils, we evaluated gastric mucosal damage, inflammatory cell infiltration and prostaglandin E2 (PGE2) concentration. We investigated whether H. pylori infection induced the COX-2 expression. Results. In H. pylori-uninfected groups, the indomethacin-treated group showed the highest mucosal damage score and the lowest PGE2 concentration. There was no difference in mucosal damage scores and PGE2 concentration between NS-398 and vehicle-alone treated group. In H. pylori-infected groups, there was no difference in mucosal damage scores, irrespective of the type of drugs administered. The indomethacin-treated group showed the lowest PGE2 concentration, similar to that of the NS-398 and vehicle-alone treated groups, both without H. pylori infection. Gastric neutrophil and monocyte infiltration scores were higher in H. pylori-infected groups than in uninfected groups. However, there was no difference in these scores according to the type of drugs administered, within H. pylori-infected or uninfected groups. COX-2 protein expression was observed in H. pylori-infected Mongolian gerbils but not in uninfected ones. Conclusions. Our animal study showed that H. pylori infection induced COX-2 expression and increased prostaglandin concentration. Administration of NSAIDs decreased the prostaglandin concentration, but did not increase mucosal damage in H. pylori-induced gastritis. Selective COX-2 inhibitors, instead of conventional NSIADs, had no beneficial effect on preventing mucosal damage in H. pylori-induced gastritis.

Magnetic susceptibility (MS) measurements were carried out for 1,120 samples in the Middle Proterozoic to Early Tertiary granitoids so far recognized in South Korea, and the lateral and spatial variation of their magnetic susceptibility, i.e., content of magnetite, is studied. The Middle Proterozoic two mica granitoids related to cassiterite (Sn) deposits in northeastern part of the Sobaegsan Massif show very low MS (less than 0.3 A- 10-3 SI unit), and the Permo-Triassic tonalitic to granodioritic and monzonitic rocks which are barren in mineralization, distributed in the middle part of South Korea also show low MS (less than 1 A- 10-3 SI unit). On the contrary the Late Triassic to Jurassic granitoids (= Daebo granitoids) which were evolved from tonalite through granodiorite to granite, and are most widely distributed in South Korea, show a wide variation on MS. Particularly in the Andong, Igsan, Gimcheon and Geochang areas, the granitoids which are barren in mineralization, are characterized by high MS (more than 10 A- 10-3 SI unit). The Chuncheon, Jecheon, Namyang and Geumsan plutons related to molybdenite (Mo) and/or wolframite or scheelite (W), and fluorite (F) mineralizations show a little high MS (more than 3 A- 10-3 SI unit). However, more than 60% of the Daebo granitoids show low MS (less than 3 A- 10-3 SI unit) and the rest show a little high MS (more than 3 A- 10-3 SI unit). Heterogeneous distribution of magnetite content in the Daebo granitoids is considered to reflect heterogeneity of redox state of the source materials for these granitoids. The Cretaceous to Early Tertiary granitoids (= Bulgugsa granitoids) in the Gyeongsang Basin had been generally evolved in the order of tonalite, diorite, granodiorite, granite and alkali-feldspar granites, which are closely related to base metal ore deposits, and mostly show higher MS (more than 3 A- 10-3 SI unit) than other granitoids mentioned above, although some exceptions are recognized in highly evolved alkali-feldspar granites (SiO2 > 76%). In contrast, as most of the highly oxidized or evolved Cretaceous granitoids distributed in areas other than the Gyeongsang Basin show lower MS than those of the Gyeongsang Basin, and appear to be magnetite free, ilmenite-series granites, but they might be hematite bearing magnetite-series granitoids. Highly oxidized nature of the Bulgugsa granitoids may be due to high Fe2O3/FeO ratio of the source materials and also high level intrusion style of the granitic magma activities. Most of the granitic rocks of the Middle Proterozoic, Permo-Triassic and more than 60% of the Late Triassic to Jurassic (Daebo granitoids) belong to ilmenite–series, however less than 40% of the Daebo granitoids and most Cretaceous ones are magnetite–series. Thus, the granitic magma intruded in Korean Peninsula became oxidized while the intrusive ages become younger.

Human malignant gliomas are highly vascularized and aggressive tumors. Angiogenesis inhibitors have been shown to induce regression of a variety of primary and metastatic tumors in vivo. However, their usefulness in treating brain tumors is not well understood. Angiostatin, a multiple kringle (1–4 of 5)–containing fragment of plasminogen, is one of the highly effective natural cryptic angiogenesis inhibitors. In our study, the therapeutic efficacy of non-glycosylated and small molecular size recombinant kringles 1–3 (rPK1–3) was examined in the treatment of brain tumors generated by stereotactic intracerebral implantation of U-87 human glioma cells in nude mice. Mice bearing tumors 7 days post-implant were treated daily with rPK1–3 (100 mg/kg) s.c. for 21 days. Treated animals showed suppressed brain tumor growth by greater than 71.2% along with a 3-fold increase of apoptotic index and suppressed vascularization by 78.9%, without any observable signs of toxicity. Analysis of bFGF and VEGF expression in the tumors of treated animals using immuno-histochemical methods showed near complete absence of growth factors. Our results indicate that the non-glycosylated, small molecular size rPK1–3 is an efficient tumoristatic agent for the treatment of intracranial human glioma xenografts in mice and might provide new strategies for the treatment of brain tumors. Int. J. Cancer 82:694–699, 1999. © 1999 Wiley-Liss, Inc.