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. 2020 Apr 1;21(4):1063-1068.
doi: 10.31557/APJCP.2020.21.4.1063.

Association between Ki-67 Labeling index and Histopathological Grading of Glioma in Indonesian Population

Emilia Theresia  1 , Rusdy Ghazali Malueka  2 , Sofia Pranacipta  1 , Bidari Kameswari  3 , Kusumo Dananjoyo  2 , Ahmad Asmedi  2 , Adiguno Suryo Wicaksono  4 , Rahmat Andi Hartanto  4 , Ery Kus Dwianingsih  1
Affiliations

Association between Ki-67 Labeling index and Histopathological Grading of Glioma in Indonesian Population

Emilia Theresia et al. Asian Pac J Cancer Prev. .

Abstract

Background: Gliomas are the most frequent primary brain tumors. According to World Health Organization guidelines, gliomas are graded into four groups (Group I-IV). This histological grading will determine prognosis and treatment of the patient. Morphological criteria are not always accurate. Tumor proliferation index is a potent quantitative marker for tumor behavior and prognosis, also it's the basis of gliomagenesis. Ki-67 immunohistochemistry examination for determining proliferation index has been suggested as an ancillary marker in deciding the definitive grading of glioma.

Objective: To analyze the correlation between Ki-67 labeling index and histopathological grading of glioma in Indonesian population.

Methods: One hundred and six formalin fixed-paraffin embedded tissue of glioma patients were collected from 4 different hospitals. Expression of Ki-67 was detected using immunohistochemistry staining and the labeling index was counted. The association between Ki-67 labeling index and histopathological grading was analyzed.

Results: Age range of patient were 1-73-years old, with male predominance (55.70%). Glioblastoma was the most common diagnosis accounting for 41.51% of all samples. Ki-67 labeling index cut point of 6.35% was obtained and significantly sensitive and specific for determining low- or high-grade glioma (p<0.001).

Conclusion: A significant association between Ki-67 labeling index and histopathological grading in Indonesian glioma patients has been revealed. The result of this study may be used to improve diagnostic and grading accuracy of glioma cases in Indonesia, especially in small biopsy specimens.<br />.

Keywords: Glioma; Indonesia; Ki-67; grading; labeling index.

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Figures

Figure 1
Figure 1
Histopathological Features of each Grade of Glioma and Its Ki-67 Labeling Index. (A) Glioma WHO grade I, sample PG-04, diagnosed as Pilocytic astrocytoma, IDH-wildtype. (A1) Microscopic appearance (HE, 400x). (A2) Immunostaining of Ki-67 with Ki-67 labeling index = 1.26% (400x). (B) Glioma WHO grade II, sample FG-66, diagnosed as Diffuse astrocytoma, IDH-wildtype. (B1) Microscopic appearance (HE, 400x). (B2) Immunostaining of Ki-67 with Ki-67 labeling index = 4.90% (400x). (C) Glioma WHO grade III, sample FG-52, diagnosed as Anaplastic oligodendroglioma, IDH-wildtype. (C1) Microscopic appearance (HE, 400x). (C2) Immunostaining of Ki-67 with Ki-67 labeling index = 16.45% (400x). (D) Glioma WHO grade IV, sample FG-71, diagnosed as Glioblastoma, IDH-mutant. (D1) Microscopic appearance (HE, 400x). (D2) Immunostaining of Ki-67 with Ki-67 labeling index = 73.55% (400x).
Figure 2
Figure 2
Average Method of Ki-67 Labeling Index Adapted from Leung et al., (2016). Counting immunopositively cells (yellow dot) from 1000 tumor cells (immunonegative cells = blue dot) using ImageJ program. Sample FG-38, WHO grade IV, diagnosed as Glioblastoma, IDH-mutant with Ki-67 labeling index results = 44.95%.
Figure 3
Figure 3
Graphs Showed ROC Curve for Ki-67 Labelling Index. From the ROC curve, using the Youden index method, optimal cut-off point in Ki-67 labeling index of 6.35% was obtained with 92% sensitivity and 93% specificity
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