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Expression of   CD133  cancer stem cell  marker in IDH-mutant  and IDH-wildtype (isocitrate dehydrogenase) astrocytoma

Original author: Sabunga OD, Kaelan C, et al. (2022) (DOI: 10.31557/APJCP.2022.23.9.3051)

Summary

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Content writer – Clinical

February 15, 2023

Introduction

Astrocytoma is a tumor that arises from the astrocytes. They belong to a group called glial cells, the supporting cells seen in the central nervous system. They are specifically called astrocytes when they are restricted to the brain or spinal cord. Astrocytomas are classified based on the histology of glial cells and malignant behavior into several subtypes. Several new classifications have emerged in recent times by including molecular parameters which are creating difficulties in evaluating and diagnosing this tumor.

 

According to recent genetic and epigenetic research, the development and prognosis of astrocytomas are significantly influenced by mutations in the IDH (Isocitrate dehydrogenase). So finding IDH mutations in the population can help in the development of chemotherapy and other targeted therapies as well. But the partial regression that is caused by this targeted therapy is typically followed by the emergence of new tumor clones that originate from the existing cancer stem cells (CSCs) population. As a result, it is believed that locating and targeting CSCs offers a potential and potent alternative for the treatment of cancer. Targeting CSCs has reportedly been linked to more significant tumor remission. It has been determined that CD133, also known as prominin-1, (a cell surface glycoprotein expressed on CSCs in several solid malignancies, including gliomas, lung, liver, and colorectal cancer) is used as a marker to identify these stem cells. So the objective of this study was  to determine the expression of this CD133 marker in IDH-mutant and IDH-wildtype astrocytomas.

Methodology

1. 67 paraffin block samples of patients with the diagnosis of diffuse astrocytoma (DA), anaplastic astrocytoma (AA), and glioblastoma (GB) from the anatomical pathology laboratory were collected.

2. Unstained slides were made from paraffin blocks and IDH1-R132H and CD133 immunohistochemistry staining was performed.

3. IDH expressions were divided into 2 groups:

  • IDH-mutant if IDH1 expression was 10% stained on the membrane and cytoplasm of tumor cells.

  • IDH-wildtype if IDH1 expression <10% stained on the membrane and cytoplasm of tumor cells.

 

4. CD133 immunoexpression was calculated using semiquantitative analysis by assessing the intensity and percentage of stained area, then the overall score was calculated by the H-score for each case by multiplying the staining intensity by the percentage of positive cells.

5. The  intensity of CD133 was  classified as :

  • uncolored: 0/negative

  • weak (visible at 400x magnification): +1

  • moderate (visible at 100x magnification): +2

  • strong (seen at 40x magnification): +3

 

6. The extensibility (area of the colored area at 400x magnification): no area is colored 0%, colored area <10%, colored area 10-50%, colored area >50%.

Results

Of the 67 samples, the distribution of astrocytoma samples based on diagnoses that are in line with histopathological grading, gender, age, tumor location based on clinical or radiological data, and the molecular status of IDH1 and CD133 were evaluated. It was found that there was a significant relationship between the expression of IDH1 and CD133 in diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma(p<0.001). Astrocytoma with IDH-mutant molecular status shows an expression of more markers of cancer stem cell CD133 than IDH-wildtype.

 

This indicates that the expression of IDH 1 and CD133 are interrelated and they play a significant role in the disease prognosis. Their determination is particularly helpful in recurrent cases of astrocytoma.

Impact of research

This study demonstrated that CD 133 stem cell marker has the potential value in astrocytomas in evaluating the :

  • Prognosis of the disease

  • The success of the treatment  employed

  • Recurrence of the disease

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