Молекулярно-цитогенетические нарушения в клетках слущенного эпителия у больных раком слизистой оболочки полости рта

E. V. Goloub; T. G. Shkavrova; V. V. Polkin; G. F. Mikhailova; V. V. Tsepenko; F. E. Sevryukov; V. S. Medvedev; P. A. Isaev

doi:10.25557/2310-0435.2019.04.69-77

E. V. Goloub A.Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Center, Obninsk, Russia http://orcid.org/0000-0002-6424-064X
T. G. Shkavrova A.Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Center, Obninsk, Russia http://orcid.org/0000-0002-7950-2585
V. V. Polkin A.Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Center, Obninsk, Russia http://orcid.org/0000-0003-0857-321X
G. F. Mikhailova A.Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Center, Obninsk, Russia http://orcid.org/0000-0003-4158-0147
V. V. Tsepenko A.Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Center, Obninsk, Russia http://orcid.org/0000-0002-5278-0809
F. E. Sevryukov A.Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Center, Obninsk, Russia http://orcid.org/0000-0002-9756-6275
V. S. Medvedev A.Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Center, Obninsk, Russia
P. A. Isaev A.Tsyb Medical Radiological Research Center, Branch of the National Medical Research Radiological Center, Obninsk, Russia http://orcid.org/0000-0001-9831-4814

DOI: https://doi.org/10.25557/2310-0435.2019.04.69-77

Keywords: oral squamous cell carcinoma (OSCC), fluorescence in situ hybridization (FISH), polysomy, EGFR, CCND1, gene amplification

Abstract

Background. According to recent conceptions molecular genetic abnormalities play a leading role in the pathogenesis of oncologic diseases. The reoccurrence and clinical significance of these abnormalities in oral squamous cell carcinoma (OSCC) are still unclear.
Aim. The aim of this study was to investigate abnormalities in the molecular cytogenetic profile of chromosomes 7, 11 and EGFR, CCND1 genes in exfoliated oral mucosa cells from OSCC patients.
Methods. The study used fluorescence in situ hybridization (FISH) with a DNA probe for EGFR/CEP7 and CCND1/CEP11. The study was conducted on tumor smears collected from 38 OSCC patients with different localizations and stages of the disease before treatment. Smears of exfoliated oral mucosa cells from 12 healthy individuals were used as the control.
Results. Cells from both healthy subjects and oral cancer patients showed deletions of gene EGFR and/or CCND1, their amplification, and monosomy and polysomy of chromosome 7 and/or 11 represented mainly by trisomy and tetrasomy. Cells with highgrade amplification of the studied genes and polysomic cells containing 5 or more centromeres were found in patients but not in control subjects. In the patient group, the average frequency of abnormalities was significantly higher (р < 0.01) than in control, including the frequencies of chromosome 7 (26.95% vs. 0.67%) and chromosome 11 (21.15% vs 0.21%) polysomy. The same was true for gene EGFR (6.45% vs. 0.13%) and gene CCND1 (14.27% vs. 0.83%) amplifications. The frequencies of cells with EGFR and CCND1 amplifications and chromosome 7 and 11 polysomy were significantly higher than in control for 79%, 79%, 95%, and 90% patients, respectively.
Conclusion. The chromosome 7 and 11 polysomy and gene EGFR and CCND1 amplifications detected in exfoliated epithelial cells of oral mucosa may be clinically significant for patients with OSCC. These disorders are markers of genome instability and may serve as prognostic factors for tumor progression, recurrence, and metastases. Moreover, they may also be potentially predictive for individual radiosensitivity, which would help individualizing therapy for patients with OSCC.

Molecular cytogenetic abnormalities in exfoliated epithelial cells of patients with oral squamous cell carcinoma

Abstract