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. 2024 Jun 20;25(12):6810.
doi: 10.3390/ijms25126810.

Evaluation of Microvascular Density in Glioblastomas in Relation to p53 and Ki67 Immunoexpression

Tamás-Csaba Sipos  1   2   3 , Attila Kövecsi  3   4 , Lóránd Kocsis  1   2 , Monica Nagy-Bota  1 , Zsuzsánna Pap  1
Affiliations

Evaluation of Microvascular Density in Glioblastomas in Relation to p53 and Ki67 Immunoexpression

Tamás-Csaba Sipos et al. Int J Mol Sci. .

Abstract

Glioblastoma is the most aggressive tumor in the central nervous system, with a survival rate of less than 15 months despite multimodal therapy. Tumor recurrence frequently occurs after removal. Tumoral angiogenesis, the formation of neovessels, has a positive impact on tumor progression and invasion, although there are controversial results in the specialized literature regarding its impact on survival. This study aims to correlate the immunoexpression of angiogenesis markers (CD34, CD105) with the proliferation index Ki67 and p53 in primary and secondary glioblastomas. This retrospective study included 54 patients diagnosed with glioblastoma at the Pathology Department of County Emergency Clinical Hospital Târgu Mureș. Microvascular density was determined using CD34 and CD105 antibodies, and the results were correlated with the immunoexpression of p53, IDH1, ATRX and Ki67. The number of neoformed blood vessels varied among cases, characterized by different shapes and calibers, with endothelial cells showing modified morphology and moderate to marked pleomorphism. Neovessels with a glomeruloid aspect, associated with intense positivity for CD34 or CD105 in endothelial cells, were observed, characteristic of glioblastomas. Mean microvascular density values were higher for the CD34 marker in all cases, though there were no statistically significant differences compared to CD105. Mutant IDH1 and ATRX glioblastomas, wild-type p53 glioblastomas, and those with a Ki67 index above 20% showed a more abundant microvascular density, with statistical correlations not reaching significance. This study highlighted a variety of percentage intervals of microvascular density in primary and secondary glioblastomas using immunohistochemical markers CD34 and CD105, respectively, with no statistically significant correlation between evaluated microvascular density and p53 or Ki67.

Keywords: CD105; CD34; IDH1; Ki67; angiogenesis; glioblastoma; p53.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Representative cases of neovessels in glioblastomas with CD34 ((A,B)—patient #16, female, 59 years of age, (C,D)—patient #29, female, 58 years of age) immunohistochemistry stain. Several aspects can be observed regarding the morphology of the examined vessels: they are organized or grouped in glomeruloid structures (arrows), have variable shapes and sizes, exhibit unequal lumens, and show endothelial cells with cyto-nuclear atypia, typically oriented towards the vessel lumen.
Figure 2
Figure 2
Representative cases of neovessels in glioblastomas with CD105 ((A)—patient #46, male, 46 years of age, (B)—patient #47, male, 67 years of age, (C)—patient #52, male, 70 years of age, (D)—patient #14, female, 63 years of age) immunohistochemistry stain. Several aspects can be observed regarding the morphology of the examined vessels: they are organized or grouped in glomeruloid structures (arrows), have variable shapes and sizes, exhibit unequal lumens, and show endothelial cells with cyto-nuclear atypia, typically oriented towards the vessel lumen.
Figure 3
Figure 3
Abundant microvascular density in glioblastomas evidenced by CD34 immunohistochemical staining. Image (A) shows a rich vascular network of different-sized vessels. Image (B) is an enlarged version of Image (A) (patient #54, female, 27 years of age). In Image (C) (patient #16, female, 59 years of age), different shades of immunohistochemical staining can be observed in endothelial cells and around these vessels; in some glial cells, a brownish coloration is visible (Image (D)) (arrows), likely due to endothelial transdifferentiation.
Figure 4
Figure 4
Microvascular density demonstrated by CD105 ((A)—patient #8, male, 45 years of age, (B–D)—patient #54, female, 27 years of age) in glioblastomas. The images suggest multiple variations in the shapes and sizes of the vascular lumens suggesting that these vascular structures are neoformed (arrows).
Figure 5
Figure 5
Normal brain tissue colored by CD105 ((A,B)—patient #54, female, 27 years of age) and CD34 ((C,D)—patient #31, male, 74 years of age) immunostaining. It can be seen that the number of vessels (arrows) is significantly lower than the tumor tissue in Figure 1, Figure 2, Figure 3 and Figure 4.
Figure 6
Figure 6
The percentage of microvascular density in glioblastomas and normal brain tissue evaluated by CD34 ((C,D)—patient #46, male, 46 years of age) and CD105 ((A,B)—patient #54, female, 27 years of age). The images suggest the number, shape, and size of vessels (arrows) in normal brain tissue compared with the glioblastoma tissue.
Figure 7
Figure 7
Correlation between microvascular density by CD34 or CD105 and laterality/orientation in glioblastomas.
Figure 8
Figure 8
Correlation between microvascular density by CD34 or CD105 and IDH1, p53, and Ki67 in glioblastomas.
Figure 9
Figure 9
Ki67 index marks endothelial cells (arrows), suggesting endothelial cell proliferation probably derived from transdifferentiated glial cells ((A–D))—patient #37, male, 41 years of age).
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