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Expression of Human Papillomavirus and the p16 Gene in Oral Potentially Malignant Disorders (OPMD): a Comparative Study With Oral Squamous Cell Carcinoma

Baddevithana AK, Jayasinghe RD, Tilakaratne WM, Illeperuma RP, Siriwardena BSMS

Appl Immunohistochem Mol Morphol, 2023 04 11;31(5):331-338.
PMID: 37036407 DOI: 10.1097/PAI.0000000000001124

BACKGROUND: The incidence of oral squamous cell carcinoma (OSCC) of the tongue is increasing in the younger population without traditional risk habits that lead researchers to find other related factors such as diet and viruses, especially human papillomavirus (HPV). It is noteworthy that many OSCCs develop from oral potentially malignant disorders (OPMDs). Correct diagnosis and timely management of OPMDs may help to prevent malignant transformation, and therefore it is worth seeing the involvement of HPV in OPMDs and oral cancers, as the preventive and curative measures in HPV-induced cancer types are different from the conventional types of OPMDs and OSCCs. Therefore, the main objective of this study was to identify a relationship between HPV and p16 in OPMDs and compare it with OSCC.
METHODS: This study was conducted on 83 cases of known OSCCs and OPMDs (oral submucous fibrosis, leukoplakia, and oral lichen planus). Assays, such as polymerized chain reaction (PCR) and reverse transcription-PCR, were carried out for HPV and p16 . The results were compared with clinical information and with the literature. The results were analyzed using SPSS 16.0 for windows.
RESULTS: P16 expression was mostly seen in males than in female patients. Out of 21 cases of keratosis with dysplasia, 19% expressed p16 . Of 26 oral lichen planus patients, 29% showed the p16 gene with immunohistochemistry. Interestingly, a high percentage of OSF cases expressed p16 (48.27%). Minimal expression was observed in OSCC (6.25%). HPV DNA was detected in 2.4% of the total sample. Both p16 and HPV were detected in a single case of OSCC. OPMDs expressed a significant amount of the p16 gene by immunohistochemistry and reverse transcription-PCR technique when compared with malignant lesions, suggesting a possible inactivation of the p16 gene. HPV and p16 are mostly negative in our OSCC sample, exhibiting low prevalence.
CONCLUSIONS: OPMDs expressed a significant amount of the p16 gene when compared with malignant lesions, suggesting a possible inactivation of the p16 gene. Although OSF expressed p16 , HPV was not detected, suggesting that over-expression could be independent of HPV. OSCC shows low HPV prevalence.

Matched MeSH terms: Genes, p16
Fulltext What We Know about the Molecular Genetics of Central Nervous System (CNS) Tumours in Malaysia

Sulong S, Yusoff AA, Zainuddin N, Abdullah JM, Pannatil JG, Jaafar H, et al.

Malays J Med Sci, 2004 Jan;11(1):37-43.
PMID: 22977358 MyJurnal

The new millennium has been regarded as a genomic era. A lot of researchers and pathologists are beginning to understand the scientific basis of molecular genetics and relates with the progression of the diseases. Central nervous system (CNS) tumours are among the most rapidly fatal of all cancers. It has been proposed that the progression of malignant tumours may result from multi-step of genetic alterations, including activation of oncogenes, inactivation of tumour suppressor genes and also the presence of certain molecular marker such as telomerase activity. In this paper, we review some recent data from the literature, including our own studies, on the molecular genetics analysis in CNS tumours. Our studies have shown that two types of tumour suppressor genes, p53 and PTEN were involved in the development of these tumours but not in p16 gene among the patients from Hospital Universiti Sains Malaysia (HUSM). Telomerase activity also has been detected in various types of CNS tumours. Thus, it is important to assemble all data which related to this study and may provide as a vital information in a new approach to neuro-oncology studies in Malaysia.

Matched MeSH terms: Genes, p16
Molecular genetic analysis of phosphatase and tensin homolog and p16 tumor suppressor genes in patients with malignant glioma

Abdullah JM, Zainuddin N, Sulong S, Jaafar H, Isa MN

Neurosurg Focus, 2003 Apr 15;14(4):e6.
PMID: 15679305

Several genes have been shown to carry mutations in human malignant gliomas, including the phosphatase and tensin homolog (PTEN) deleted on chromosome 10 and p16 tumor suppressor genes. Alterations of this gene located on chromosome 10 q23 and 9p21, respectively, may contribute to gliomagenesis. In this study, the authors analyzed 20 cases of malignant gliomas obtained in patients living on the east coast of Malaysia to investigate the possibilities of involvement of the PTEN and p16 genes.

Matched MeSH terms: Genes, p16/physiology*
Fulltext Presence of telomerase activity with undetectable p16 gene mutation in Malaysian patients with brain tumor

Jafri AM, Sarina S, George PJ, Nizam IM

Med J Malaysia, 2004 Oct;59(4):480-5.
PMID: 15779580 MyJurnal

Recent study has shown that activation of the telomerase and p16 gene mutation are both necessary for tumorigenesis. Our objectives were to detect telomerase activity and investigate the possibility of p16 gene mutations in various types of brain tumor. We analyzed 23 tumor tissues collected in 2000 to 2002. Telomerase activity was detected by a TRAP assay using a TRAPEZE Telomerase Detection Kit (Intergen, Co). PCR-SSCP (Single Strand Conformation Polymorphism) analysis was performed to screen for p16 gene mutation at exon 1 and 2. The activity was detected in 26.1% of the brain tumor samples and mostly present in high-grade tumors. There was a significant association between telomerase activity status and tumor grade but not with patient criteria. Telomerase activity was detected in the analyzed tumors, supporting the fact that activation of telomerase is an important feature for tumorigenesis. There was no mobility shift of p16 gene using SSCP and suggested no mutation at exon 1 and 2 occurred in all samples. These results suggest that another mechanism of p16 gene alterations could be involved and associated with detectable telomerase activity in the progression of tumors.

Matched MeSH terms: Genes, p16/physiology*
p16 gene expression in basal cell carcinoma

Eshkoor SA, Ismail P, Rahman SA, Oshkour SA

Arch Med Res, 2008 Oct;39(7):668-73.
PMID: 18760195 DOI: 10.1016/j.arcmed.2008.06.003

Basal cell carcinoma (BCC) develops predominantly in sun-exposed skin in fair-skinned individuals prone to sunburn. BCC typically occurs in adults. High exposure to ultraviolet (UV) radiation increases rate of developing BCC, a slowly growing tumor that occurs in hair-growing squamous epithelium and rarely metastasizes. In genetic studies, BCC patients have cell-cycle abnormalities of different parts of the signaling pathway. Retinoblastoma regulatory pathway is important in cell cycle arrest. In this pathway, p16INK4a, an inhibitor of Rb pathway, binds to CDK4 and CDK6 competitively with cyclin D1 to prevent phosphorylation of tumor suppressor pRB gene. Alteration of this pathway contributes to development of human cancers and also is effective in skin cancers. In this study, we analyzed mRNA expression using in situ RT-PCR and the role of immunohistochemical expression of p16INK4a in BCC.

Matched MeSH terms: Genes, p16*
Expression and alteration of p16 in diffuse large B cell lymphoma

Lee ES, Kim LH, Abdullah WA, Peh SC

Pathobiology, 2010;77(2):96-105.
PMID: 20332669 DOI: 10.1159/000278291

This study aimed to examine (1) the expression of P16 protein relative to sites of presentation, immunophenotypic subgroups and proliferative indices of tumour cells, and (2) the relationship between p16 gene alterations and P16 protein overexpression in 70 cases of diffuse large B cell lymphoma (DLBCL).

Matched MeSH terms: Genes, p16*
Fulltext Effect of perivitelline fluid from horseshoe crab on the expression of cell cycle regulatory genes in human dental pulp stem cells

Abdul Qawee Rani, Thirumulu Ponnuraj Kannan, Nur Izyan Azmi, Najian Binti Ibrahim, Nor Shamsuria Omar, Ahmad Azlina, et al.

Archives of Orofacial Sciences, 2016;11(1):7-14.
MyJurnal

Perivitelline fluid (PVF) of the horseshoe crab embryo has been reported to possess an important role
during embryogenesis by promoting cell proliferation. This study aims to evaluate the effect of PVF on the
expression of cell cycle regulatory genes from human dental pulp stem cells (DPSCs) between different cell
passages viz. 4, 5, 6. The cells were treated with a single dose of PVF (26.89 mg/ml) PVF. Gene expression was
quantified for CDKNA2A, PTEN, MDM2 and TP53 genes using reverse transcriptase PCR. CDKN2A and MDM2
expression for treated and untreated DPSCs, expressed a similar pattern of expression. The higher expression of
CDKN2A showed that the treatment increased cell proliferation and prevented cell senescence. DPSCs with PVF
treatment showed increased expression of MDM2 at passage 4 and drastically declined expression at passage 5
and slightly increased at passage 6. TP53 expression of DPSCs treated group showed a higher expression
compared to untreated group. On the other hand, the expression of PTEN in DPSCs treated group started to
increase from passage 5 to 6. However, on the whole, the PTEN expression was higher than the untreated group
in all the passages studied here. The results showed that PVF could enhance cell cycle regulatory gene
expression in DPSCs as indicated by the higher expression of all the genes considered in this study at different
cell passages in the treated group compared to the untreated group. Mann Whitney test was utilized to determine
the significance of cell cycle regulatory genes expression between treated and untreated group. Significant
difference in expression of genes between the treated and untreated groups were found at all passages except
for CDKN2A gene whereby, its expression was not significantly different at passage 5 though it did express
slightly higher in PVF treated DPSCs.

Matched MeSH terms: Genes, p16
p16 Tumor Suppressor Gene Methylation in Diffuse Large B Cell Lymphoma: A Study of 88 Cases at Two Hospitals in the East Coast of Malaysia

Mohd Ridah LJ, A Talib N, Muhammad N, Hussain FA, Zainuddin N

Asian Pac J Cancer Prev, 2017 10 26;18(10):2781-2785.
PMID: 29072413

Introduction: p16 gene plays an important role in the normal cell cycle regulation. Methylation of p16 has been reported to be one of the epigenetic events contributing to the pathogenesis of diffuse large B-cell lymphoma (DLBCL) which occurring at varying frequency. DLBCL is an aggressive and high-grade malignancy which accounts for approximately 30% of all non-Hodgkin lymphoma cases. However, little is known regarding the epigenetic alterations of p16 gene in DLBCL cases in Malaysia. Therefore, the objective of this study was to examine the status of p16 methylation in DLBCL. Methods: A total of 88 formalin-fixed paraffin-embedded DLBCL tissues retrieved from two hospitals located in the east coast of Malaysia, namely Hospital Tengku Ampuan Afzan (HTAA) Pahang and Hospital Universiti Sains Malaysia (HUSM) Kelantan, were chosen for this study. DNA specimens were isolated and subsequently subjected to bisulfite treatment prior to methylation specific-PCR. Two pairs of primers were used to amplify methylated and unmethylated regions of p16 gene. The PCR products were then separated using agarose gel electrophoresis and visualised under UV illumination. SPSS version 12.0 was utilised to perform all statistical analysis. Result: p16 methylation was detected in 65 of 88 (74%) samples. There was a significant association between p16 methylation status and patients aged >50 years old (p=0.04). Conclusion: Our study demonstrated that methylation of p16 tumor suppressor gene in our DLBCL cases is common and significantly increased among patients aged 50 years and above. Aging is known to be an important risk factor in the development of cancers and we speculate that this might be due to the increased transformation of malignant cells in aging cell population. However, this has yet to be confirmed with further research and correlate the findings with clinicopathological parameters.

Matched MeSH terms: Genes, p16
High-risk human papillomavirus infection in different histological subtypes of renal cell carcinoma

Farhadi A, Behzad-Behbahani A, Geramizadeh B, Sekawi Z, Rahsaz M, Sharifzadeh S

J Med Virol, 2014 Jul;86(7):1134-44.
PMID: 24700118 DOI: 10.1002/jmv.23945

Limited data exist regarding whether a high-risk human papillomavirus (HR-HPV) infection increases the risk of developing renal cell carcinoma. The aim of this study was to investigate whether HPV infection has a role in the pathogenesis or development of a certain histological subtype of renal cell carcinoma. Formalin-fixed paraffin-embedded (FFPE) specimens of 122 patients with histopathologically proven renal cell carcinoma and their respective peritumoral tissues were examined. The presence of HPV-DNA was determined by a combination of MY/GP+ consensus primers and HPV-16/18 type specific nested PCRs followed by direct sequencing. Catalyzed signal-amplified colorimetric in situ hybridization (CSAC-ISH) technique was applied to determine the physical status of viral genome. The expression of p16INK4a and HPV L1 capsid proteins was evaluated using immunohistochemistry. HPV genome was detected in 37 (30.3%) tumor specimens and their four (4.1%) corresponding peritumoral tissues. HPV-18 was the most common viral type identified followed by HPV-16 and 58. Immunoexpression of p16INK4a was detected in 24 (20.3%) cases. Data analysis showed a significant correlation between p16INK4a expression and the presence of HR-HPV DNA (P

Matched MeSH terms: Genes, p16