Glomerular Fingerprint Deposits In Hepatitis B Virus-associated Nephropathy

Fingerprint deposits have been considered as a characteristic feature of lupus nephritis. We report such deposits in a case with hepatitis B virus-associated membranoproliferative glomerulonephritis. The patient did not show any sign of systemic lupus erythematosus at time of biopsy or during a 3· year follow-up period

Synchronous mucosal Schwann-cell hamartomas in a young adult suggestive of mucosal Schwann-cell harmatomatosis: a case report

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Mucosal Schwann-cell hamartoma is a rare mesenchymal polyp that presents in the intestine. Despite lacking ganglion cells, it resembles a gastrointestinal ganglioneuroma. Case presentation We report a case of synchronous mucosal Schwann-cell hamartomas in a young male patient, who presented with a single discrete polyp in the mid-rectum and multiple polypoid mucosal lesions in the distal rectum. Conclusion To the best of our knowledge, this is the first report of a case of multiple mucosal Schwann-cell hamartomas

Multiplicity of Advanced T Category–Tumors Is a Risk Factor for Survival in Patients with Colorectal Carcinoma

Background Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. Methods Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. Results SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151). Conclusions Findings suggested that multiplicity of advanced T category–tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer’s tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC

Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma

ECC: Extrahepatic cholangiocarcinoma; ICC: Intrahepatic cholangiocarcinoma; IG: Intraductal growth; LINE-1: Long interspersed element-1; MF: Mass-forming; PI: Periductal infiltrative; TNM: Tumor, node, and metastasisAbstract Background DNA methylation changes occurring in cancer cells are featured with both promoter CpG island hypermethylation and diffuse genomic hypomethylation. Long interspersed element-1 (LINE-1) is repeated in an interspersed manner with an estimated 500,000 copies per genome. LINE-1 has its CpG sites of the 5′ untranslated region methylated heavily in normal cells and undergoes demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas. Methods A total of 172 cases of intrahepatic cholangiocarcinomas were analyzed for their methylation levels at four CpG sites of LINE-1 using bisulfite pyrosequencing. We examined the relation between tumoral LINE-1 methylation level and clinicopathological features, including survival. Results Tumor differentiation, lymphatic invasion, and T stage were associated with a low average methylation level of LINE-1 at the four CpG sites; LINE-1 methylation level tended to be lower in high-grade differentiation, lymphatic emboli, and higher T stage. LINE-1 hypomethylation was significantly linked with lower cancer-specific survival in patients with intrahepatic cholangiocarcinoma and was found to be an independent prognostic parameter. Conclusions Our findings suggest that tumoral LINE-1 hypomethylation could be a molecular biomarker heralding poor prognosis of patients with intrahepatic cholangiocarcinoma. Our findings need to be validated in further study.This work was supported by a grant from the National Research Foundation (NRF) grants funded by the Korean Ministry of Science, ICT and Future Planning (2011–0030049 and 2016M3A9B6026921), a grant from the Priority Research Centers Program through the NRF (2009–0093820), and a grant from the Korea Health Technology R & D Project through the Korea Health Industry Development Institute funded by the Korean Ministry of Health and Welfare (HI14C1277). The funding bodies had no role in the design of the study, the collection, analysis, and interpretation of the data, or in the writing of the manuscript

Immunohistochemical and Molecular Characteristics of Follicular Patterned Thyroid Nodules with Incomplete Nuclear Features of Papillary Thyroid Carcinoma

Background : Follicular patterned thyroid nodules with incomplete nuclear features of papillary thyroid carcinoma (FTN-INPTCs) are difficult to diagnose, and their biological behavior and association with follicular variants of PTC (FVPTCs) have not yet been established. The aim of this study is to determine immunohistochemical and molecular characteristics of FTN-INPTCs. Methods : We investigated immunohistochemical features (galectin-3, HBME-1, CK19, fibronectin-1, CITED1), BRAF V600E mutation and RASSF1A promoter methylation status in 30 FTN-INPTC cases, along with 26 FVPTCs, 21 follicular adenomas (FAs) and 14 nodular hyperplasias (NHs). Results : Expression of galectin-3, HBME-1, CK19 and CITED1 was significantly higher in FTN-INPTCs than in FAs or NHs, but expression of galectin-3, CK19 and fibronectin-1 was lower in FTN-INPTCs than in FVPTCs. The BRAF V600E mutation was not detected in the benign nodules or FTN-INPTCs, whereas 57% of FVPTCs had the mutation. RASSF1A promoter methylation was higher in FTN-INPTCs than in benign nodules but there was no difference between FTN-INPTCs and FVPTCs. Conclusions : Our results represent the borderline immunohistochemical and molecular characteristics of FTN-INPTC. We conclude that FTN-INPTC is an intermediate lesion between a benign nodule and a FVPTC, and that it is pathogenetically related to FVPTC.This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2006- 331-E00050).Arora N, 2008, WORLD J SURG, V32, P1237, DOI 10.1007/s00268-008-9484-1Park YJ, 2007, J KOREAN MED SCI, V22, P621CHAN JKC, 2007, DIAGNOSTIC HISTOPATH, P997Rhoden KJ, 2006, J CLIN ENDOCR METAB, V91, P2414, DOI 10.1210/jc.2006-0240de Matos PS, 2005, HISTOPATHOLOGY, V47, P391, DOI 10.1111/j.1365-2559.2005.02221.xNakamura N, 2005, LAB INVEST, V85, P1065, DOI 10.1038/labinvest.3700306Xing M, 2005, ENDOCR-RELAT CANCER, V12, P245, DOI 10.1677/erc.1.0978Papotti M, 2005, MODERN PATHOL, V18, P541, DOI 10.1038/modpathol.3800321Prasad ML, 2005, MODERN PATHOL, V18, P48, DOI 10.1038/modpathol.3800235Weisenberger DJ, 2005, NUCLEIC ACIDS RES, V33, P6823, DOI 10.1093/nar/gki987Vasko VV, 2004, EUR J ENDOCRINOL, V151, P779Kim KH, 2004, YONSEI MED J, V45, P818Gasbarri A, 2004, BRIT J CANCER, V91, P1096, DOI 10.1038/sj.bjc.6602097Xing MZ, 2004, CANCER RES, V64, P1664Kimura ET, 2003, CANCER RES, V63, P1454Hirokawa M, 2002, AM J SURG PATHOL, V26, P1508Schagdarsurengin U, 2002, CANCER RES, V62, P3698Fusco A, 2002, AM J PATHOL, V160, P2157Shivakumar L, 2002, MOL CELL BIOL, V22, P4309, DOI 10.1128/MCB.22.12.4309-4318.2002Coli A, 2002, HISTOPATHOLOGY, V40, P80Bartolazzi A, 2001, LANCET, V357, P1644Eads CA, 2001, CANCER RES, V61, P3410Williams ED, 2000, INT J SURG PATHOL, V8, P181Orlandi F, 1998, CANCER RES, V58, P3015Sack MT, 1997, MODERN PATHOL, V10, P668Herman JG, 1996, P NATL ACAD SCI USA, V93, P9821OKAYASU I, 1995, CANCER, V76, P2312BERHO M, 1995, ANN CLIN LAB SCI, V25, P513RAPHAEL SJ, 1994, MODERN PATHOL, V7, P295ROSAI J, 1992, ATLAS TUMOR PATHOL, P65

Prognostic implications and interaction of L1 methylation and p53 expression statuses in advanced gastric cancer

Background TP53 is frequently mutated across various tissue types of cancers. In normal cells, long interspersed nuclear element-1 (LINE-1, L1) is mostly repressed by DNA methylation in its 5′ untranslated region but is activated by DNA demethylation process during tumorigenesis. p53 is indispensable for maintaining genomic stability and plays its role in controlling genomic stability by repressing retrotransposon activity. However, it is unclear whether p53 regulates expression or methylation of L1 differently depending on the mutational status of TP53. Four hundred ninety cases of advanced gastric cancer (AGC) were analyzed for their statuses in p53 expression and L1 methylation using immunohistochemistry and pyrosequencing, respectively. Whether L1 methylation and expression statuses were differently affected by types of TP53 mutants was analyzed in gastric cancer cell line. Results By p53 immunohistochemistry, tumors were classified into 4 groups according to the intensity and extent of stained tumor nuclei. L1 methylation level was significantly higher in p53 expression group 1 than in the other groups in which L1 methylation level was similar (P <  0.001). Although L1 methylation and p53 expression statuses were associated with patient survival, multivariate analysis revealed that L1 methylation was an independent prognostic parameter. In in vitro analysis of AGS cells with the introduction of wild type or mutant types of TP53, L1 methylation level and activity were different depending on types of TP53 mutation. Conclusions Findings suggest that L1 methylation level is affected by TP53 mutation status; although, L1 methylation status was an independent prognostic parameter in patients with AGC. Further study is required to elucidate the mechanism of how wild type or mutant p53 affects L1 activity and methylation status of L1 CpG island.This work was supported by a grant from the National Research Foundation (NRF) funded by the Korean Ministry of Science, ICT and Future Planning (2016M3A9B6026921), and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Korean Ministry of Health and Welfare (HI14C1277)

Epigenetic Subgroups of Esophageal and Gastric Adenocarcinoma with Differential GATA5 DNA Methylation Associated with Clinical and Lifestyle Factors

BACKGROUND: Adenocarcinomas located near the gastroesophageal junction have unclear etiology and are difficult to classify. We used DNA methylation analysis to identify subtype-specific markers and new subgroups of gastroesophageal adenocarcinomas, and studied their association with epidemiological risk factors and clinical outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We used logistic regression models and unsupervised hierarchical cluster analysis of 74 DNA methylation markers on 45 tumor samples (44 patients) of esophageal and gastric adenocarcinomas obtained from a population-based case-control study to uncover epigenetic markers and cluster groups of gastroesophageal adenocarcinomas. No distinct epigenetic differences were evident between subtypes of gastric and esophageal cancers. However, we identified two gastroesophageal adenocarcinoma subclusters based on DNA methylation profiles. Group membership was best predicted by GATA5 DNA methylation status. We analyzed the associations between these two epigenetic groups and exposure using logistic regression, and the associations with survival time using Cox regression in a larger set of 317 tumor samples (278 patients). There were more males with esophageal and gastric cardia cancers in Cluster Group 1 characterized by higher GATA5 DNA methylation values (all p<0.05). This group also showed associations of borderline statistical significance with having ever smoked (p-value = 0.07), high body mass index (p-value = 0.06), and symptoms of gastroesophageal reflux (p-value = 0.07). Subjects in cluster Group 1 showed better survival than those in Group 2 after adjusting for tumor differentiation grade, but this was not found to be independent of tumor stage. CONCLUSIONS/SIGNIFICANCE: DNA methylation profiling can be used in population-based studies to identify epigenetic subclasses of gastroesophageal adenocarcinomas and class-specific DNA methylation markers that can be linked to epidemiological data and clinical outcome. Two new epigenetic subgroups of gastroesophageal adenocarcinomas were identified that differ to some extent in their survival rates, risk factors of exposure, and GATA5 DNA methylation