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Lin W.-L.,Chung Shan Medical University | Kuo W.-H.,Armed Force Hualien General Hospital | Kuo W.-H.,Central Taiwan University of Science and Technology | Chen F.-L.,Chung Shan Medical University | And 6 more authors.
Annals of Surgical Oncology | Year: 2011

Background: Although overexpression, amplification, and somatic mutation of the HER2 gene have been noted in various types of human cancers, we report here for the first time that novel mutations and amplification of the HER2 gene occurred concomitantly in mucinous epithelial ovarian cancer (EOC). Methods: Twenty-seven tissue microarray samples from EOC patients were analyzed by immunohistochemistry (IHC) with Dako c-erb-B2 antibody and subsequently were examined by fluorescence in situ hybridization (FISH) with the Abbott PathVysion HER2 DNA Probe Kit. HER2 gene, exon 18-24, encoding a tyrosine kinase domain, was analyzed by polymerase chain reaction (PCR) and direct sequencing. Results: The FISH-IHC paired results confirmed 19 concordant negative results and 3 concordant positive results. Moreover, all 4 HER2-amplified cases were of the mucinous type, whereas the remaining 23 HER2-nonamplified cases were of the nonmucinous type. The 4 mucinous EOC cases with HER2 gene amplification were selected and further analyzed for HER2 gene mutations. Data revealed that somatic mutations were present in 2 cases (R970W and E971G), but absent in the other 2 cases. Conclusions: HER2 protein overexpression correlated significantly with HER2 gene amplification in EOC (P = 0.027). It is surprising that all 4 cases of mucinous EOC showed HER2 gene amplification confirmed by FISH testing. However, we suppose that increasing the number of cases would possibly modify the results. This study also showed that both HER2 gene amplification and somatic mutations are not mutually exclusive in mucinous EOC. Further studies are warranted to investigate the potential role of anti-HER2 therapy. © 2011 Society of Surgical Oncology. Source

Liao W.-C.,National Taiwan University Hospital | Liao W.-C.,National Taiwan University | Wang H.-P.,National Taiwan University Hospital | Huang H.-Y.,National Taiwan University Hospital | And 7 more authors.
Clinical and Translational Gastroenterology | Year: 2012

OBJECTIVES: Liver metastasis develops in 60% of patients after resection of pancreatic adenocarcinoma (PAC) and carries a dismal prognosis, but factors predictive of liver recurrence are poorly understood. Experimental evidence suggests that liver metastasis of PAC is mediated by CXCL12/CXCR4 signaling and can be inhibited by CXCR4 antagonist. We aimed to verify whether CXCR4 expression predicts early liver recurrence and poor survival after resection, and to explore the usefulness of CXCR4 status for prognosis prediction. METHODS: Ninety-seven consecutive PAC patients undergoing R0 resection were analyzed. CXCR4 expression was analyzed by immunohistochemistry, and its associations with liver recurrence-free survival and overall survival were analyzed by Kaplan- Meier estimates and multivariable Cox and accelerated failure time regression models. RESULTS: CXCR4-positive patients had a worse prognosis than CXCR4-negative patients, with a shorter liver recurrence-free survival (median: 8.7 vs. 39.7 months; P=0.004) and overall survival (median: 10.2 vs. 22.3 months; P<0.001). Overall survival for CXCR4-positive stage IIa patients was similar to that for stage IIb patients and significantly shorter than that for CXCR4- negative stage IIa patients (median: 9.7 vs. 27.4 months; P=0.002). CXCR4 positivity was significantly associated with liver recurrence (adjusted hazard ratio 2.22, 95% confidence interval (CI) 1.15-4.30; P=0.018) and predicted a 46% (95% CI 9-68%) and 35% (95% CI 7-54%) reduction in liver recurrence-free survival and overall survival, respectively. CONCLUSIONS: Tumor CXCR4 expression independently predicts early liver recurrence and poor overall survival after resection of PAC. CXCR4 status stratifies stage IIa patients into two groups with a striking difference in prognosis. Clinical and Translational Gastroenterology (2012) 3, e22; doi:10.1038/ctg.2012.18; published online 13 September 2012 Subject Category: Liver. © 2012 the American College of Gastroenterology. Source

Wang V.-C.,Cardinal Tien Hospital | Wang V.-C.,Fu Jen Catholic University | Suen J.-H.,Taipei Institute of Pathology | Chuang T.-C.,Tamkang University | Kao M.-C.,China Medical University at Taichung
Acta Neurologica Taiwanica | Year: 2011

Purpose: This study aimed to determine the genetic role of HER2, one of the epidermal growth factor receptor (EGFR) family, in schwannoma. The latter is a neogrowth of myelin-producing Schwann cells in peripheral nerves, inducible by N-nitrosoethylurea in animals with mutation in the neu gene (homologous gene of human HER2 protein). Methods: In this study we obtained genomic DNA samples from tissue blocks of schwannoma, initially by xylene treatment and alcohol extraction, followed by use of the DNA extraction kit. Evaluation of this genetic polymorphism in our subjects was conducted by direct nucleotide sequencing or restriction enzyme analyses after PCR work. Results: There were thirty extracted DNA samples from tissue blocks of schwannoma, and all were Ile/Ile homozygotes after genotype analyses. Two individuals received the leukocyte DNA extraction after peripheral blood sampling, both showing Ile/Ile homozygosity. This study gave the impression of an association of the HER2 polymorphism at codon 655 with tumorigenesis of schwannoma. Although the majority of the Taiwanese showed Ile/Ile homozygosity (about 83%), the present study revealed a 100% carriage rate among the tissue blocks from our subjects with schwannoma. Conclusion: Ile/Ile homozygosity at codon 655 of HER2 in schwannoma may imply some role in tumorigenesis of Ile655Val allele of HER2 in this nerve tumor. Source

Tai C.-M.,I - Shou University | Tai C.-M.,Kaohsiung Medical University | Huang C.-K.,I - Shou University | Hwang J.-C.,I - Shou University | And 6 more authors.
Obesity Surgery | Year: 2012

Background: Obesity is a risk factor for nonalcoholic fatty liver disease (NAFLD), which appears to improve after weight loss induced by bariatric surgery in Western countries. The present study aims to determine the alterations of clinical measurements and liver histology of NAFLD after bariatric surgery in morbidly obese Chinese patients. Methods: Between November 2006 and December 2007, 21 morbidly obese patients receiving intra-operative liver biopsy and follow-up liver biopsy 1 year after laparoscopic Roux-en-Y gastric bypass were enrolled. NAFLD activity score (NAS) and fibrosis stage were histologically evaluated. Results: The mean body mass index fell from 43.8±7.5 to 28.3±4.6 kg/m2 (P<0.01). Biochemical improvement was found in serum levels of alanine aminotransferase (P<0.01) and γ- glutamyltransferase (P<0.01), but not aspartate aminotransferase (P=0.66). Histological improvement was noted in NAS (P<0.01) and individual components, including steatosis (P<0.01), ballooning degeneration (P<0.01), and lobular inflammation (P=0.02). Pre-operatively, 4 (19.0%), 11 (52.4%), and 6 (28.6%) patients were found to have NAS ≧5, 3 or 4, and ≦2, respectively. All patients had NAS ≦2 after surgery. Fibrosis stage also showed significant improvement (P<0.01). Conclusions: Bariatric surgery can achieve a dramatic improvement of NAFLD both biochemically and histologically in morbidly obese Chinese patients. © 2011 Springer Science + Business Media, LLC. Source

Tai C.-L.,Taipei Veterans General Hospital | Tai C.-L.,Shenyang University | Liu M.-Y.,Taipei Veterans General Hospital | Yu H.-C.,Taipei Veterans General Hospital | And 13 more authors.
Clinica Chimica Acta | Year: 2012

Background: As an X-linked genetic disorder, Fabry disease was first thought to affect males only, and females were generally considered to be asymptomatic carriers. However, recent research suggests that female carriers of Fabry disease may still develop vital organ damage causing severe morbidity and mortality. In the previous newborn screening, from 299,007 newborns, we identified a total of 20 different Fabry mutations and 121 newborns with Fabry mutations. However, we found that most female carriers are not detected by enzyme assays. Methods: A streamlined method for high resolution melting (HRM) analysis was designed to screen for GLA gene mutations using a same PCR and melting program. Primer sets were designed to cover the 7 exons and the Chinese common intronic mutation, IVS4+919G>A of GLA gene. Results: The HRM analysis was successful in identifying heterozygous and hemizygous patients with the 20 surveyed mutations. We were also successful in using this method to test dry blood spots of newborns afflicted with Fabry mutations without having to determine DNA concentration before PCR amplification. Conclusion: The results of this study show that HRM could be a reliable and sensitive method for use in the rapid screening of females for GLA mutations. © 2011 Elsevier B.V. Source

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