Proliferative Index in Pediatric Pilocytic Astrocytoma by Region of Origin and Prediction of Clinical Behavior

Abstract

Background/Aims: Pilocytic astrocytomas are common pediatric tumors. Molecular profiles vary with location of origin. Comparisons of proliferation have not been reported. We sought to identify differences in growth by region and whether these predict clinical behavior. Methods: A retrospective review of all patients undergoing surgery for a pilocytic astrocytoma at Children’s Hospital LA from 2003 to 2015 was completed. Tumor location, determined by imaging, was stratified into infratentorial, supratentorial, or optic pathway. Proliferation was measured by Ki-67 immunostaining. A p value of 0.05 was deemed significant. Results: 77 patients were identified. 51 had posterior fossa tumors, 12 had supratentorial tumors, and 14 had optic pathway tumors. Mean Ki-67 score was 3.67, 4.09, and 3.83%, respectively (p = 0.82). Ki-67 of ≥4% trended towards recurrence (p = 0.11), incomplete resection (p = 0.15), and younger age at presentation (p = 0.04). Ki-67 was weakly correlated with shorter survival after surgery (r = –0.103, p = 0.41). Partial resection strongest predicted recurrence (p < 0.001; OR = 13.0). Conclusion: Proliferative index does not change by location. Higher cell proliferation was seen in younger patients and associated with shorter time to and a higher risk of recurrence. Further study is needed to identify predictors for clinical behavior. Importance of Study: This study provides a detailed analysis of the proliferative indices of tumors arising from characteristic locations within the brain. With recent advances in our understanding of the differences in molecular and genetic profiles despite similar histologic diagnoses, we felt that it was important to review whether there were unique components of tumor behavior that could be identified. In turn, we sought to determine whether tumor behavior could be used to predict the clinical course. This knowledge is important, given that not every tumor may undergo complete surgical resection, and that some lesions may require more aggressive upfront adjuvant therapy or be closely monitored for recurrence.

Prognostic utility and characteristics of MIB-1 labeling index as a proliferative activity marker in childhood low-grade glioma: a retrospective observational study

“…In 2003, Bowers et al reported of a study including 118 Pilocytic astrocytoma (PA) patients, showing a shortened PFS in patients with tumors bearing a MIB-1 LI > 2%. This data is in line with four subsequent studies on PAs including 35–80 cases, reporting a significant negative correlation of KI-67/MIB-1 LI and PFS (Fisher et al 2002 ; Dorward et al 2010 ; Margraf et al 2011 ; Tu et al 2018 ). In contrast, Horbinski et al ( 2010 ) published a case series including 118 patients, showing no correlation of MIB-1 LI and adverse treatment outcome including recurrence, progression, metastatic spread or death.…”

“…While nowadays amending an integral part to histopathological routine diagnostics in CNS tumors, assessment of MIB-1 LI has previously shown to contribute to differentiation of the degree of malignancy in tumors of the central nervous system, while a significant correlation to WHO grade in human glioma has been reported (Matsumoto et al 1998 ; Pollack et al 2002 ; Skjulsvik et al 2014 ; Hsu et al 1997 ; Krishnan et al 2019 ). However, as compared to distinct solid CNS and non-CNS malignancies, previous analyses of smaller PLGG cohorts addressing the prognostic value of KI-67/MIB-1 LI in PLGG, many of them from the pre-molecular era, draw conflicting conclusions and necessitate further assessment (Bowers et al 2002 , 2003 ; Fisher et al 2002 ; Dorward et al 2010 ; Margraf et al 2011 ; Tu et al 2018 ; Horbinski et al 2010 ; Cherlow et al 2019 ; Cler et al 2022 ).…”

“…The prognostic significance of MIB-1 labeling index (LI) in PLGG, however, remains unclear, as previously published data of smaller case series partly show contradictory results and draw conflicting conclusions (Bowers et al 2002 , 2003 ; Fisher et al 2002 ; Dorward et al 2010 ; Margraf et al 2011 ; Tu et al 2018 ; Horbinski et al 2010 ; Cherlow et al 2019 ; Cler et al 2022 ). In 2003, Bowers et al reported of a study including 118 Pilocytic astrocytoma (PA) patients, showing a shortened PFS in patients with tumors bearing a MIB-1 LI > 2%.…”

Human induced pluripotent stem cell engineering establishes a humanized mouse platform for pediatric low-grade glioma modeling

“…2 c). The glioma tumor areas exhibited low proliferative indices (4–6% Ki67 + cells), within the upper range of proliferation rates seen in pediatric PAs [ 64 ], whereas the embryonal-like areas exhibited slightly higher proliferative rates (8–15% Ki67 + cells) (Fig. 2 a, c).…”

Genetic and histopathological associations with outcome in pediatric pilocytic astrocytoma

“…Histopathological features such as vascular hyalinization and proliferation, calcifications, and necrosis have been associated with reduced PFS; 21,22 however, these associations are not consistently observed across studies. 7 The Ki-67 proliferative index has been associated with reduced PFS, 15,23,24 but this finding has also been inconsistent. 22 Increased cellularity has been observed in recurrent tumors, 25 but a causal relationship between cellularity in initial tumors and PFS has not been established.…”