Despite several molecular signatures for "lower grade diffuse gliomas" (LGG) have been identified, WHO grade still remains a cornerstone of treatment guidelines. Mitotic count bears a crucial role in its definition, although limited by the poor reproducibility of standard Hematoxylin & Eosin (H&E) evaluation. Phospho-histone-H3 (PHH3) and Ki-67 have been proposed as alternative assays of cellular proliferation. Therefore in the present series of 141 LGG, the molecular characterization (namely IDH status, 1p/19q co-deletion and MGMT promoter methylation) was integrated with the tumor "proliferative trait" (conventional H&E or PHH3-guided mitotic count and Ki-67 index) in term of prognosis definition. Exclusively high PHH3 and Ki-67 values were predictor of poor prognosis (log rank test, P = 0.0281 for PHH3 and P = 0.032 for Ki-67), unlike standard mitotic count. Based on Cox proportional hazard regression analyses, among all clinical (age), pathological (PHH3 and Ki-67) and molecular variables (IDH, 1p/19q codeletion and MGMT methylation) with a prognostic relevance at univariate survival analysis, only IDH expression (P = 0.001) and Ki-67 proliferation index (P = 0.027) proved to be independent prognostic factors. In addition, stratifying by IDH expression status, high Ki-67 retained its prognostic relevance uniquely in the IDH negative patient (P = 0.029) doubling their risk of death (hazard ratio = 2.27). Overall, PHH3 immunostaining is the sole reliable method with a prognostic value to highlight mitotic figures in LGG. Ki-67 proliferation index exceeds PHH3 mitotic count as a predictor of patient's prognosis, and should be integrated with molecular markers in a comprehensive grading system for LGG.

Ki-67 proliferation index but not mitotic thresholds integrates the molecular prognostic stratification of lower grade gliomas

DUREGON, ELEONORA;BERTERO, LUCA;SOFFIETTI, Riccardo;Rudà, Roberta;TREVISAN, MORENA;PAPOTTI, Mauro Giulio;SENETTA, REBECCA;CASSONI, Paola
Last
2016-01-01

Abstract

Despite several molecular signatures for "lower grade diffuse gliomas" (LGG) have been identified, WHO grade still remains a cornerstone of treatment guidelines. Mitotic count bears a crucial role in its definition, although limited by the poor reproducibility of standard Hematoxylin & Eosin (H&E) evaluation. Phospho-histone-H3 (PHH3) and Ki-67 have been proposed as alternative assays of cellular proliferation. Therefore in the present series of 141 LGG, the molecular characterization (namely IDH status, 1p/19q co-deletion and MGMT promoter methylation) was integrated with the tumor "proliferative trait" (conventional H&E or PHH3-guided mitotic count and Ki-67 index) in term of prognosis definition. Exclusively high PHH3 and Ki-67 values were predictor of poor prognosis (log rank test, P = 0.0281 for PHH3 and P = 0.032 for Ki-67), unlike standard mitotic count. Based on Cox proportional hazard regression analyses, among all clinical (age), pathological (PHH3 and Ki-67) and molecular variables (IDH, 1p/19q codeletion and MGMT methylation) with a prognostic relevance at univariate survival analysis, only IDH expression (P = 0.001) and Ki-67 proliferation index (P = 0.027) proved to be independent prognostic factors. In addition, stratifying by IDH expression status, high Ki-67 retained its prognostic relevance uniquely in the IDH negative patient (P = 0.029) doubling their risk of death (hazard ratio = 2.27). Overall, PHH3 immunostaining is the sole reliable method with a prognostic value to highlight mitotic figures in LGG. Ki-67 proliferation index exceeds PHH3 mitotic count as a predictor of patient's prognosis, and should be integrated with molecular markers in a comprehensive grading system for LGG.
2016
7
16
21190
21198
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=8498&path%5B%5D=25250
Ki-67 index; Lower grade gliomas; Pathology Section; Phospho-histone H3; Prognosis; Oncology
Duregon, Eleonora; Bertero, Luca; Pittaro, Alessandra; Soffietti, Riccardo; Rudà, Roberta; Trevisan, Morena; Papotti, Mauro; Ventura, Laura; Senetta, Rebecca; Cassoni, Paola
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1562011
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