Ultrastructural evidence for presenсe of gap junctions in rare case of pleomorphic xanthoastrocytoma

ABSTRACT

The phenomenon of unstable expression of gap junction’s proteins connexins remains a “visiting card” of astrocytic tumors with various degrees of malignancy. At the same time, it stays unclear what is detected by the positive expression of connexins in astrocytic tumors: gap junctions, hemi-channels, or connexin proteins in cytosol. In the present work, for the first time, we demonstrate an ultrastructural evidence of gap junctions in pleomorphic xanthoastrocytoma, a rare primary brain tumor, the intercellular characteristics of which are poorly studied and remain very discursive and controversial. The primary tumor mass was resected during craniotomy from a 57-old patient diagnosed with pleomorphic xanthoastrocytoma Grade II based on the histopathological analysis. The immunohistochemical study was conducted with primary antibodies: Neurofilament, Myelin basic protein, Glial fibrillary acidic protein, and Synaptophysin. For electron microscopic examination fragments of tumor tissue were fixed in a glutaraldehyde, postfixed in a 1% OsO₄, dehydrated and embedded into resin. After the detailed clinical, histological, and immunohistochemical study we revealed some ultrastructural characteristics of the tumor, as well as the first evidence of direct intercellular connection between the tumor cells via gap junctions. Regularly arranged gap junctions connected the somas of xanthastrocytes with dark cytoplasm containing lipid drops. Besides the localization between the cell bodies, from one to several gap junctions were found between the branches of xanthoastrocytoma in tumor intercellular space in close proximity to tumor cell. Our results may indicate gap junctions as a possible structure for intercellular communication between pleomorphic xanthoastrocytoma cells.

KEYWORDS:

• Astrocytic tumor
• electron microscopy
• gap junction
• pleomorphic xanthoastrocytoma

Contribution statement

Evgeniya Yu. Kirichenko conceived and designed the study, researched and analysed data, wrote, edited and reviewed the manuscript. Sehweil Salah carried out the surgery and tracked the patient, wrote, and reviewed the manuscript. Sergey S. Todorov conducted a pathomorphological expertise. Zoya A. Goncharova made nucleic acid extraction and PCR analysis. Marina A. Akimenko conducted an immunohistochemical study. Alexander K. Logvinov prepared and processed specimens for TEM. Svetlana Yu. Filippova and Aleksei G. Nikitin edited and reviewed the manuscript. All authors gave final approval for publication. Evgeniya Yu. Kirichenko takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by the Ministry of Education and Science of Russian Federation, grant № 6.6047.2017/8.9 and Russian Foundation for Basic Research project 19-015-00325/19