AIM： To clarify the significance of JC virus （JCV） T-antigen （T-Ag） expression in human gastric cancer. METHODS： We investigated the relationship between TAg detected by immunohistochemistry and Epstein- Barr vi...AIM： To clarify the significance of JC virus （JCV） T-antigen （T-Ag） expression in human gastric cancer. METHODS： We investigated the relationship between TAg detected by immunohistochemistry and Epstein- Barr virus （EBV） infection, microsatellite instability （MSI）, and genetic and epigenetic alterations in gastric cancers. Mutations in the p53,β-catenin, K/MS, BRAF, PIK3CA genes were analyzed by PCR- single strand conformation polymorphism and DNA sequencing. Allelic losses were determined by PCR at 7 microsatellite loci. Aberrant DNA methylation was analyzed by MethyLight assay. RESULTS： JCV T-Ag protein expression was found in 49% of 90 gastric cancer tissues. TAg positivity was not correlated with clinicopathological characteristics. TAg expression was detected in a similar percentage of EBV positive cancers （4 of 9, 44%） and EBV negative cancers （35 of 73, 48%）. TAg expression was detected in a significantly lower percentage of MSI-H cancers （14%） than in non MSI-H cancers （55%, P = 0.005）. TAg expression was detected in a significantly higher percentage of cancers with nuclear/cytoplasmic localization of β-catenin （15 of 21, 71%） than in cancers without （42%, P = 0.018）. p53 mutations were detected in a significantly lower percentage of T-Ag positive cancers （32%） than in TAg negative cancers （57%, P = 0.018）. TAg positive gastric cancers showed a significant increase in the allelic losses and aberrant methylation compared with T-Ag negative gastric cancers （P = 0.008 and P = 0.003）. CONCLUSION： The results suggest that JCV T-Ag is involved in gastric carcinogenesis through multiple mechanisms of genetic and epigenetic alterations.展开更多
AIM: To investigate the neuropathology of the brain in a rare case of remission following diagnosis of progressive multifocal leukoencephalopathy(PML).METHODS: Consent from the family for an autopsy was obtained, clin...AIM: To investigate the neuropathology of the brain in a rare case of remission following diagnosis of progressive multifocal leukoencephalopathy(PML).METHODS: Consent from the family for an autopsy was obtained, clinical records and radiograms were retrieved. A complete autopsy was performed, with brain examination after fixation and coronal sectioning at 1 cm intervals. Fourteen regions were collected for paraffin embedding and staining for microscopic analysis. Histologic sections were stained with Luxol blue, hematoxylin/eosin, and immunostained for myelin basic protein, neurofilament, SV40 T antigen and p53. The biopsy material was also retrieved and sections were stained with hematoxylin/eosin and immunostained for SV40 and p53. Sections were examined by American Board of Pathology certified pathologists and images captured digitally.RESULTS: Review of the clinical records was notable for a history of ulcerative colitis resulting in total colectomy in 1977 and a liver transplant in 1998 followed by immune-suppressive therapy. Neurological symptoms presented immediately, therefore a biopsy was obtained which was diagnosed as PML. Immunotherapy was adjusted and clinical improvement was noted. No subsequent progression was reported. Review of the biopsy demonstrated atypical astrocytes and enlarged hyperchromatic oligodendroglial cells consistent with JC virus infection. Strong SV40 and p53 staining was found in glial cells and regions of dense macrophage infiltration were present. On gross examination of the post-mortem brain, a lesion in the same site as the original biopsy in the cerebellum was identified but no other lesions in the brain were found. Microscopic analysis of this cerebellar lesion revealed a loss of myelin and axons, and evidence of axonal damage. This single burned-out lesion was equivocally positive for SV40 antigen with little p53 staining. Examination of thirteen other brain regions found no other occult sites.CONCLUSION: Our study reveals residual damage, rare macrophages or other inflammation and minimal evidence of persistent virus. This case demonstrates the possibility of complete remission of PML.展开更多
Proportional to the growth rate of its clinical expression, the last decades have seen an increase on JC Virus diagnosis testing, and on therapeutic and symptoms management plans. Whether isolated or associated to ret...Proportional to the growth rate of its clinical expression, the last decades have seen an increase on JC Virus diagnosis testing, and on therapeutic and symptoms management plans. Whether isolated or associated to retroviral therapy, the relationship of JC Virus to HIV allowed us to delve a little deeper into the knowledge of its behavior. Now as new immune-modulating and immune-suppressing therapies are developed, its clinical expression has become broader and more complexly, thereby our need is to develop more precise diagnosis and therapeutic plans.展开更多
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology of Japan(Yamamoto H,Imai K and Shinomura Y)Grants-in-Aid for Cancer Research from the Ministry of Health,Laborand Welfare of Japan(Yamamoto H)
文摘AIM： To clarify the significance of JC virus （JCV） T-antigen （T-Ag） expression in human gastric cancer. METHODS： We investigated the relationship between TAg detected by immunohistochemistry and Epstein- Barr virus （EBV） infection, microsatellite instability （MSI）, and genetic and epigenetic alterations in gastric cancers. Mutations in the p53,β-catenin, K/MS, BRAF, PIK3CA genes were analyzed by PCR- single strand conformation polymorphism and DNA sequencing. Allelic losses were determined by PCR at 7 microsatellite loci. Aberrant DNA methylation was analyzed by MethyLight assay. RESULTS： JCV T-Ag protein expression was found in 49% of 90 gastric cancer tissues. TAg positivity was not correlated with clinicopathological characteristics. TAg expression was detected in a similar percentage of EBV positive cancers （4 of 9, 44%） and EBV negative cancers （35 of 73, 48%）. TAg expression was detected in a significantly lower percentage of MSI-H cancers （14%） than in non MSI-H cancers （55%, P = 0.005）. TAg expression was detected in a significantly higher percentage of cancers with nuclear/cytoplasmic localization of β-catenin （15 of 21, 71%） than in cancers without （42%, P = 0.018）. p53 mutations were detected in a significantly lower percentage of T-Ag positive cancers （32%） than in TAg negative cancers （57%, P = 0.018）. TAg positive gastric cancers showed a significant increase in the allelic losses and aberrant methylation compared with T-Ag negative gastric cancers （P = 0.008 and P = 0.003）. CONCLUSION： The results suggest that JCV T-Ag is involved in gastric carcinogenesis through multiple mechanisms of genetic and epigenetic alterations.
基金Supported by The Harvey Family Endowment(ELB)National Institutes of Health RO1 MH096093,RO1 NS062184,and RO1 NS046810
文摘AIM: To investigate the neuropathology of the brain in a rare case of remission following diagnosis of progressive multifocal leukoencephalopathy(PML).METHODS: Consent from the family for an autopsy was obtained, clinical records and radiograms were retrieved. A complete autopsy was performed, with brain examination after fixation and coronal sectioning at 1 cm intervals. Fourteen regions were collected for paraffin embedding and staining for microscopic analysis. Histologic sections were stained with Luxol blue, hematoxylin/eosin, and immunostained for myelin basic protein, neurofilament, SV40 T antigen and p53. The biopsy material was also retrieved and sections were stained with hematoxylin/eosin and immunostained for SV40 and p53. Sections were examined by American Board of Pathology certified pathologists and images captured digitally.RESULTS: Review of the clinical records was notable for a history of ulcerative colitis resulting in total colectomy in 1977 and a liver transplant in 1998 followed by immune-suppressive therapy. Neurological symptoms presented immediately, therefore a biopsy was obtained which was diagnosed as PML. Immunotherapy was adjusted and clinical improvement was noted. No subsequent progression was reported. Review of the biopsy demonstrated atypical astrocytes and enlarged hyperchromatic oligodendroglial cells consistent with JC virus infection. Strong SV40 and p53 staining was found in glial cells and regions of dense macrophage infiltration were present. On gross examination of the post-mortem brain, a lesion in the same site as the original biopsy in the cerebellum was identified but no other lesions in the brain were found. Microscopic analysis of this cerebellar lesion revealed a loss of myelin and axons, and evidence of axonal damage. This single burned-out lesion was equivocally positive for SV40 antigen with little p53 staining. Examination of thirteen other brain regions found no other occult sites.CONCLUSION: Our study reveals residual damage, rare macrophages or other inflammation and minimal evidence of persistent virus. This case demonstrates the possibility of complete remission of PML.
文摘Proportional to the growth rate of its clinical expression, the last decades have seen an increase on JC Virus diagnosis testing, and on therapeutic and symptoms management plans. Whether isolated or associated to retroviral therapy, the relationship of JC Virus to HIV allowed us to delve a little deeper into the knowledge of its behavior. Now as new immune-modulating and immune-suppressing therapies are developed, its clinical expression has become broader and more complexly, thereby our need is to develop more precise diagnosis and therapeutic plans.
