Zixi Yang1, Feng Ling1, Sibei Ruan1, Jiajia Hu2, Mingxi Tang1, Xingwang Sun1, Wenbo Long1. 1. Pathology Department of the First Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, People's Republic of China. 2. School of Basic Medicine, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
Abstract
BACKGROUND AND OBJECTIVE: Genetic alterations, including IDH, BRAF, and TERT promoter mutations (IDH-mu, BRAF-mu, TERTp-mu, respectively), 1p/19q co-deletion (1p/19q-codel), and MGMT promoter methylation (MGMTp-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diagnosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood. METHODS: We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II-IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry. RESULTS: In the 103 cases, MGMTp-M was the most common alteration (70.9%), followed by TERTp-mu (58.3%), IDH-mu (46.6%), 1p/19q-codel (34.0%), and BRAF-mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (IDH-mu/TERTp-mu/MGMTp-M/1p/19q-codel). The percentage of TERTp-mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of IDH-mu and 1p/19q-codel cases decreased with Ki-67 expression. IDH-mu, MGMTp-M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while TERTp-mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, IDH-mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis. CONCLUSION: IDH-mu only and quadruple-positivity were associated with good OS in glioma patients, while TERTp-mu only, TERTp-mu/MGMTp-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.
BACKGROUND AND OBJECTIVE: Genetic alterations, including IDH, BRAF, and TERT promoter mutations (IDH-mu, BRAF-mu, TERTp-mu, respectively), 1p/19q co-deletion (1p/19q-codel), and MGMT promoter methylation (MGMTp-M), are correlated with glioma tumor development. Therefore, these genetic alterations could serve as biomarkers for the diagnosis, prognosis, and classification of gliomas, combined with the immunohistochemical markers Ki-67 and p53. However, the correlation between these alterations and the expression of Ki-67 and p53 is poorly understood. METHODS: We analyzed the prevalence and prognosis of these five alterations, as well as Ki-67 and p53 expression, in 103 primary grade II-IV gliomas via fluorescence qPCR, Sanger sequencing, fluorescence in situ hybridization, and immunohistochemistry. RESULTS: In the 103 cases, MGMTp-M was the most common alteration (70.9%), followed by TERTp-mu (58.3%), IDH-mu (46.6%), 1p/19q-codel (34.0%), and BRAF-mu (5.8%). No cases showed quintuple-positive alterations, but 26 cases (25.2%) showed quadruple-positive alterations (IDH-mu/TERTp-mu/MGMTp-M/1p/19q-codel). The percentage of TERTp-mu and 1p/19q-codel cases decreased with p53 expression, and the percentage of IDH-mu and 1p/19q-codel cases decreased with Ki-67 expression. IDH-mu, MGMTp-M, and 1p/19q-codel were positive factors for survival rates in glioma patients, while TERTp-mu, p53, and Ki-67 positivity were negative factors. Old age, histological grade IV, IDH-mu, 1p/19q-codel, Ki-67+, and p53+/Ki-67+ were significantly correlated with overall survival (OS). However, only p53+/Ki-67+ was an independent prognostic factor for OS in the multivariate Cox-model analysis. CONCLUSION: IDH-mu only and quadruple-positivity were associated with good OS in glioma patients, while TERTp-mu only, TERTp-mu/MGMTp-M and p53+/Ki-67+ were associated with poor prognosis. Combining these genomic alterations and Ki-67/p53 expression should have clinical value in gliomas.
Authors: Eva Schulze Heuling; Felix Knab; Josefine Radke; Eskil Eskilsson; Emmanuel Martinez-Ledesma; Arend Koch; Marcus Czabanka; Christoph Dieterich; Roel G Verhaak; Christoph Harms; Philipp Euskirchen Journal: Mol Cancer Res Date: 2017-02-01 Impact factor: 5.852
Authors: Huy Gia Vuong; Ahmed M A Altibi; Uyen N P Duong; Hanh T T Ngo; Thong Quang Pham; Aden Ka-Yin Chan; Chul-Kee Park; Kar-Ming Fung; Lewis Hassell Journal: Crit Rev Oncol Hematol Date: 2017-10-03 Impact factor: 6.312
Authors: Christian Hartmann; Jochen Meyer; Jörg Balss; David Capper; Wolf Mueller; Arne Christians; Jörg Felsberg; Marietta Wolter; Christian Mawrin; Wolfgang Wick; Michael Weller; Christel Herold-Mende; Andreas Unterberg; Judith W M Jeuken; Peter Wesseling; Guido Reifenberger; Andreas von Deimling Journal: Acta Neuropathol Date: 2009-06-25 Impact factor: 17.088
Authors: Jeanette E Eckel-Passow; Daniel H Lachance; Annette M Molinaro; Kyle M Walsh; Paul A Decker; Hugues Sicotte; Melike Pekmezci; Terri Rice; Matt L Kosel; Ivan V Smirnov; Gobinda Sarkar; Alissa A Caron; Thomas M Kollmeyer; Corinne E Praska; Anisha R Chada; Chandralekha Halder; Helen M Hansen; Lucie S McCoy; Paige M Bracci; Roxanne Marshall; Shichun Zheng; Gerald F Reis; Alexander R Pico; Brian P O'Neill; Jan C Buckner; Caterina Giannini; Jason T Huse; Arie Perry; Tarik Tihan; Mitchell S Berger; Susan M Chang; Michael D Prados; Joseph Wiemels; John K Wiencke; Margaret R Wrensch; Robert B Jenkins Journal: N Engl J Med Date: 2015-06-10 Impact factor: 176.079
Authors: M Labussière; A L Di Stefano; V Gleize; B Boisselier; M Giry; S Mangesius; A Bruno; R Paterra; Y Marie; A Rahimian; G Finocchiaro; R S Houlston; K Hoang-Xuan; A Idbaih; J-Y Delattre; K Mokhtari; M Sanson Journal: Br J Cancer Date: 2014-10-14 Impact factor: 7.640