Clinicopathological correlations and cellular dynamics in a murine model of oral carcinogenesis

Cheyenne Coscia Bueno; Isadora Peres Klein; Michael Everton Andrades; Luise Meurer; Rogério Moraes de Castilho; Caroline Peres Klein; Vivian Petersen Wagner; Manoela Domingues Martins; Vinicius Coelho Carrard

doi:10.5327/2525-5711.290

Autores

Cheyenne Coscia Bueno Federal University of Rio Grande do Sul, School of Dentistry, Department of Conservative Dentistry – Porto Alegre (RS), Brazil. https://orcid.org/0009-0009-7942-6963
Isadora Peres Klein Federal University of Rio Grande do Sul, School of Dentistry, Department of Conservative Dentistry – Porto Alegre (RS), Brazil. https://orcid.org/0000-0003-1912-0654
Michael Everton Andrades Clinics Hospital of Porto Alegre, Molecular and Protein Analysis Unit – Porto Alegre (RS), Brazil. https://orcid.org/0000-0003-0337-9661
Luise Meurer Federal University of Rio Grande do Sul, School of Medicine, Department of Pathology – Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-1315-4899
Rogério Moraes de Castilho University of Michigan, Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine – Ann Arbor, Michigan, United States of America. https://orcid.org/0000-0001-5358-612X
Caroline Peres Klein Federal University of Rio Grande do Sul, Institute of Basic Health Science, Biochemistry – Porto Alegre (RS), Brazil. https://orcid.org/0009-0000-6447-8140
Vivian Petersen Wagner University of São Paulo, School of Dentistry, Department of Oral Medicine – São Paulo (SP), Brazil. https://orcid.org/0000-0002-1447-2135
Manoela Domingues Martins Federal University of Rio Grande do Sul, School of Dentistry, Department of Conservative Dentistry – Porto Alegre (RS), Brazil. https://orcid.org/0000-0001-8662-5965
Vinicius Coelho Carrard Federal University of Rio Grande do Sul, School of Dentistry, Department of Conservative Dentistry – Porto Alegre (RS), Brazil. https://orcid.org/0000-0002-1624-0178

DOI:

https://doi.org/10.5327/2525-5711.290

Palavras-chave:

Mouth neoplasms, Carcinogenesis, Cell proliferation, Cell transformation, Neoplastic, Biomarkers

Resumo

Objective: To investigate clinicopathological correlations, cell proliferation, and immortalization during induced oral carcinogenesis. Methods: Forty-three Wistar rats were divided into a control group (n=10) or a 4-Nitroquinoline 1-oxide (4NQO) group (n=33). Control animals were euthanized after 20 weeks, and 4NQO-treated animals after 4 (n=10), 12 (n=10), or 20 weeks (n=13). Oral lesions were classified macroscopically and histologically, with Ki-67 and BMI-1 immunolabeling used to assess cell proliferation and immortalization. Results: Histological alterations, including hyperplasia/hyperkeratosis (n=4) and severe dysplasia (n=2), were observed in clinically normal mucosa. Leukoplakic lesions exhibited varying severity, ranging from hyperplasia/hyperkeratosis (n=3) to squamous cell carcinoma (SCC, n=2). Most SCCs appeared as ulcers (n=3) or nodules (n=4). Ki-67 expression increased progressively with histopathological changes, while BMI-1 levels rose significantly in later stages. A positive correlation was found between Ki-67 and BMI-1 (R=0.33, p=0.03). Conclusion: Cellular alterations often precede visible clinical lesions. Clinical appearances, particularly of leukoplakic lesions, frequently did not align with histopathological findings. Proliferation and immortalization were interconnected but occurred at distinct stages of carcinogenesis.

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