Mutational Signatures in Mandibular Ameloblastoma Correlate with Smoking

Objective: To study the clinocopathological factors and presence of Human Pappiloma Virus in ameloblastoma by immnohistochemistry. Methods: It was a cross sectional study on 50 surgical specimens of ameloblastoma, completed in six months. These were selected and processed for initial screening by H&E and then by immunohistochemistry (IHC) for detection of Human Papilloma Virus (HPV). The questionnaire was designed to study the clinicopathological factors associated in these patients. Sections of 4µm were cut, placed on special positive charged glass slides in the Department of Pathology, King Edward Medical University. It was then examined by the histopathologists for grading and scoring of these lesions. Chi Square test was used to assess the differences found in types of ameloblastomas. The p-value was smaller than 0.05 (p < 0.05). Results: The mean age of the patients (12-80 years old) was 38.6±15.1 years, with male-female ratio 2.84: 1. HPV was positive in 9 (18%), whereas negative in of 41 (82%) patients. Among the positive, reactive HPV with score-1 was 8 and score-2 was 1. According to histological variant, follicular was present in 78%, Plexiform pattern in 8%, Conventional and Desmoplastic variants in one patient each; and Cystic and Acanthomatous were seen in two and three patients respectively. The mandible was involved in 39 patients, maxilla and right maxilla involved in 4 patients each, right retromolar, cheek and angle of mandible was seen in one patient each. About 16% patients had anterior, 66% had posterior and 18% had both anterior and posterior regions involved. Among the HPV positive reactive statistically, no significant difference was found with smoking, Paan and exposure to pesticides, factory or mine (p-value > 0.05). Among HPV positive reactive patients, eight had ameloblastoma whereas, 1 had ameloblastomic fibroma. There was no statistical significance of type, location and region of tumor in HPV positivity. Conclusion: Mandible and posterior region was more commonly involved. Follicular pattern was most common. There was no effect of exposure to pesticides, factory or mine, smoke and human papilloma virus in the etiology of ameloblastoma because only 18% of patients showed the association of HPV16 doi: https://doi.org/10.12669/pjms.35.6.909 How to cite this:Ali M, Bukhari MH, Hassan F, Illyas M. Clinicopathological study of ameloblastoma and detection of human papilloma virus by immunohistochemistry. Pak J Med Sci. 2019;35(6):1691-1696. doi: https://doi.org/10.12669/pjms.35.6.909 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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“…In the present study only 18% patients were smokers and 82% were non smokers. This study agrees with that of Guan et al 2019 25…”

Section: Discussionsupporting

confidence: 94%

Clinicopathological study of ameloblastoma and detection of human papilloma virus by immunohistochemistry

et al. 2019

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“…Recently, Guan et al . ( 6 ) reported a Whole-Exome Sequencing (WES) study on Ameloblastoma and confirmed the influence of tobacco on the somatic mutation, supporting its role in the tumorigenesis.…”

Section: Introductionmentioning

confidence: 92%

“…Due to the invasive potential and high recurrent rate, the surgical resection often has a margin of at least 1 cm from the margin of the tumor, leading to profound facial defects and morbidity ( 2 ). Conservative options like enucleation or curettage often result in a high recurrence rate ( 5 , 6 ). The alternative management of radiation therapy has a limited application in Ameloblastoma because of the risk of malignant transformation ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Whole exome sequencing and system biology analysis support the "two-hit" mechanism in the onset of Ameloblastoma

Shi¹,

Li²,

Yu³

et al. 2021

Med Oral

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Background Ameloblastoma is the most frequent odontogenic tumor. Various evidence has highlighted the role of somatic mutations, including recurrent mutation BRAF V600E, in the tumorigenesis of Ameloblastoma, but the intact genetic pathology remains unknown. Material and Methods We sequenced the whole exome of both tumor tissue and healthy bone tissue from four mandibular ameloblastoma patients. The identified somatic mutations were integrated into Weighted Gene Co-expression Network Analysis on publicly available expression data of odontoblast, ameloblast, and Ameloblastoma. Results We identified a total of 70 rare and severe somatic mutations. We found BRAF V600E on all four patients, supporting previous discovery. HSAP4 was also hit by two missense mutations on two different patients. By applying Weighted Gene Co-expression Network Analysis on expression data of odontoblast, ameloblast, and Ameloblastoma, we found a proliferation-associated gene module that was significantly disrupted in tumor tissues. Each patient carried at least two rare, severe somatic mutations affecting genes within this module, including HSPA4, GNAS, CLTC, NES, and KMT2D. All these mutations had a ratio of variant-support reads lower than BRAF V600E, indicating that they occurred later than BRAF V600E. Conclusions We suggest that a severe somatic mutation on the gene network of cell proliferation other than BRAF V600E, namely second hit, may contribute to the tumorigenesis of Ameloblastoma. Key words: Ameloblastoma, whole exome sequencing, somatic mutation, BRAF, HSPA4, two-hit theory.

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“…Ameloblastoma (AB), a common odontogenic epithelial neoplasm, exhibits locally invasive and aggressive behaviors ( 1 ). More than 80% of AB cases occur in the mandible ( 2 ). It has up to 90% risk of recurrence following conservative treatment ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-1-3p Suppresses Malignant Phenotypes of Ameloblastoma Through Down-Regulating Lysosomal Associated Membrane Protein 2-Mediated Autophagy

et al. 2021

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Objective: Several clinical trials have suggested that autophagy inhibition is a promising approach for cancer therapy. However, the implications of autophagy in ameloblastoma (AB) remain undiscovered. This study investigated the dysregulated autophagy and its regulatory mechanisms in AB.Methods: The expression and distribution of autophagy-related proteins including B-cell lymphoma-2-interacting protein-1 (Beclin1), microtubule-associated protein 1 light chain 3 (LC3) II/I and lysosomal associated membrane protein 2 (LAMP2) were detected in AB and normal oral mucosa (NOM) tissues by immunohistochemistry and western blot analyses. Under transmission electron microscopy, the autophagy of AB was observed. LAMP2 was a potential target mRNA of miR-1-3p. Quantitative Real-time PCR (qRT-PCR) analysis was utilized for examining LAMP2 and miR-1-3p in AB tissues as well as AM-1 cells. The correlation between LAMP2 and miR-1-3p was analyzed in AB. After transfection with miR-1-3p mimic or inhibitor, LAMP2 expression, proliferation, migration, and invasion were separately detected in AM-1 cells. Rescue assays were finally presented.Results: Our results showed that Beclin1 was lowly expressed as well as LC3II/I and LAMP2 were highly expressed in AB. Autophagosomes were observed in AB. MiR-1-3p was lowly expressed in AB, which exhibited negative correlations to LAMP2 expression. MiR-1-3p up-regulation significantly lowered LAMP2 expression in AM-1 cells. Furthermore, miR-1-3p overexpression restrained proliferative, migrated, and invasive capacities of AM-1 cells, which were ameliorated by LAMP2 overexpression.Conclusion: Our findings demonstrated that miR-1-3p suppressed malignant phenotypes of AB through down-regulating LAMP2-mediated autophagy, which could become an underlying target for AB therapy.

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Mutational Signatures in Mandibular Ameloblastoma Correlate with Smoking

Cited by 16 publications

References 38 publications

Clinicopathological study of ameloblastoma and detection of human papilloma virus by immunohistochemistry

Clinicopathological study of ameloblastoma and detection of human papilloma virus by immunohistochemistry

Whole exome sequencing and system biology analysis support the "two-hit" mechanism in the onset of Ameloblastoma

MicroRNA-1-3p Suppresses Malignant Phenotypes of Ameloblastoma Through Down-Regulating Lysosomal Associated Membrane Protein 2-Mediated Autophagy

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