Skip to main content

Advertisement

SpringerLink
Log in

p53 and p16 expression in oral cavity squamous cell and basaloid squamous cell carcinoma

  • Original Article
  • Published:
Oral Cancer

Abstract

Purpose

The true aggressive behavior of oral cavity BSCC compared to SCC has been debated, and the study of disturbances in cell cycle proteins may help understand the biological behavior in both variants. The aim of this study was to investigate the p53 and p16 status in 32 SCC and 16 BSCC of oral cavity.

Methods

Immunohistochemistry was used to assess these proteins’ status. The association between p53 and p16 with clinico-pathological features and prognostic value were evaluated.

Results

A high prevalence of p53 disruption was observed in both variants (84.4% of 32—SCC and 81.2% of 16—BSCC; p = 0.78). The BSCC showed a higher prevalence of high p16 expression (86.7% of 15) when compared to SCC (61.3% of 31); however, this difference did not reach statistical significance (p = 0.08). In the SCC variant, cases with high p16 expression showed a lower overall survival. Protein p53 showed association with tobacco use, but with no other clinico-pathological features.

Conclusions

Our results suggest that p53 and p16 cell cycle disruptions are common findings in oral cavity SCC, as well as in BSCC. A higher prevalence of p16 overexpression in oral BSCC cases may be related to carcinogenesis process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Zini A, Czerninski R, Sgan-Cohen HD (2010) Oral cancer over four decades: epidemiology, trends, histology, and survival by anatomical sites. J Oral Pathol Med 39:299–305

    Article  PubMed  Google Scholar 

  2. Ralli M, Singh S, Yadav SP, Sharma N, Verma R, Sen R (2016) Assessment and clinicopathological correlation of p16 expression in head and neck squamous cell carcinoma. J Cancer Res Ther 12:232–237

    Article  PubMed  Google Scholar 

  3. de Sampaio Góes FC, Oliveira DT, Dorta RG, Nishimoto IN, Landman G, Kowalski LP (2004) Prognoses of oral basaloid squamous cell carcinoma and squamous cell carcinoma: a comparison. Arch Otolaryngol Head Neck Surg 130:83–86

    Article  PubMed  Google Scholar 

  4. Fritsch VA, Lentsch EJ (2014) Basaloid squamous cell carcinoma of the larynx: analysis of 145 cases with comparison to conventional squamous cell carcinoma. Head Neck 36:164–170

    Article  PubMed  Google Scholar 

  5. Jayasooriya PR, Tilakaratne WM, Mendis BR, Lombardi T (2013) A literature review on oral basaloid squamous cell carcinomas, with special emphasis on etiology. Ann Diagn Pathol 17:547–551

    Article  PubMed  Google Scholar 

  6. Pereira CH, Morais MO, Martins AF, Soares MQ, de Alencar RC, Batista AC et al (2016) Expression of adhesion proteins (E-cadherin and β-catenin) and cell proliferation (Ki-67) at the invasive tumor front in conventional oral squamous cell and basaloid squamous cell carcinomas. Arch Oral Biol 61:8–15

    Article  PubMed  Google Scholar 

  7. Bellizzi AM, Woodford RL, Moskaluk CA, Jones DR, Kozower BD, Stelow EB (2009) Basaloid squamous cell carcinoma of the esophagus: assessment for high-risk human papillomavirus and related molecular markers. Am J Surg Pathol 33:1608–1614

    Article  PubMed  Google Scholar 

  8. Chernock RD, Lewis JS Jr, Zhang Q, El-Mofty SK (2010) Human papillomavirus-positive basaloid squamous cell carcinomas of the upper aerodigestive tract: a distinct clinicopathologic and molecular subtype of basaloid squamous cell carcinoma. Hum Pathol 41:1016–1023

    Article  PubMed  Google Scholar 

  9. Jacobi C, Ayx I, Fritsche K, Piontek G, Hoffmann D, Weirich G et al (2015) Potential impact of human papillomavirus on survival of basaloid squamous carcinoma of the head and neck. Oncotarget 6:3462–3470

    Article  PubMed  Google Scholar 

  10. Califano J, van der Riet P, Westra W, Nawroz H, Clayman G, Piantadosi S et al (1996) Genetic progression model for head and neck cancer: implications for field cancerization. Can Res 56:2488–2492

    Google Scholar 

  11. Reshmi S, Gollin S (2005) Chromosomal instability in oral cancer cells. J Dent Res 84:107–117

    Article  PubMed  Google Scholar 

  12. Fischer NW, Prodeus A, Malkin D, Gariépy J (2016) p53 oligomerization status modulates cell fate decisions between growth, arrest and apoptosis. Cell Cycle 15:3210–3219

    Article  PubMed  PubMed Central  Google Scholar 

  13. Karpathiou G, Monaya A, Forest F, Froudarakis M, Casteillo F, Dumollard J et al (2016) p16 and p53 expression status in head and neck squamous cell carcinoma: a correlation with histological, histoprognostic and clinical parameters. Pathology 48:341–348

    Article  PubMed  Google Scholar 

  14. Suh Y, Amelio I, Guerrero Urbano T, Tavassoli M (2014) Clinical update on cancer: molecular oncology of head and neck cancer. Cell Death Dis. https://doi.org/10.1038/cddis.2013.548

    Google Scholar 

  15. Shah NG, Trivedi TI, Tankshali RA, Goswami JV, Jetly DH, Shukla SN et al (2009) Prognostic significance of molecular markers in oral squamous cell carcinoma: a multivariate analysis. Head Neck 31:1544–1556

    Article  PubMed  Google Scholar 

  16. Vallonthaiel AG, Singh MK, Dinda AK, Kakkar A, Thakar A, Das SN (2016) Expression of cell cycle-associated proteins p53, pRb, p16, p27, and correlation with survival: a comparative study on oral squamous cell carcinoma and verrucous carcinoma. Appl Immunohistochem Mol Morphol 24:193–200

    Article  PubMed  Google Scholar 

  17. Yuen PW, Chow V, Choy J, Lam KY, Ho WK, Wei WI (2001) The clinicopathologic significance of p53 and p21 expression in the surgical management of lingual squamous cell carcinoma. Am J Clin Pathol 116:240–245

    Article  PubMed  Google Scholar 

  18. Mane DR, Kale AD, Angadi P, Hallikerimath S (2013) Expression of cytokeratin subtypes: MMP-9, p53, and αSMA to differentiate basaloid squamous cell carcinoma from other basaloid tumors of the oral cavity. Appl Immunohistochem Mol Morphol 21:431–443

    Article  PubMed  Google Scholar 

  19. Sampaio-Góes FC, Oliveira DT, Dorta RG, Nonogaki S, Landman G, Nishimoto I et al (2005) Expression of PCNA, p53, BAX, and Bcl-X in oral poorly differentiated and basaloid squamous cell carcinoma: relationships with prognosis. Head Neck 27:982–989

    Article  PubMed  Google Scholar 

  20. Romagosa C, Simonetti S, López-Vicente L, Mazo A, Lleonart ME, Castellvi J et al (2011) p16Ink4a overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors. Oncogene 30:2087–2097

    Article  PubMed  Google Scholar 

  21. Satgunaseelan L, Virk SA, Lum T, Gao K, Clark JR, Gupta R (2016) p16 expression independent of human papillomavirus is associated with lower stage and longer disease-free survival in oral cavity squamous cell carcinoma. Pathology 48:441–448

    Article  PubMed  Google Scholar 

  22. Zhao N, Ang MK, Yin XY, Patel MR, Fritchie K, Thorne L et al (2012) Different cellular p16(INK4a) localisation may signal different survival outcomes in head and neck cancer. Br J Cancer 107:482–490

    Article  PubMed  PubMed Central  Google Scholar 

  23. Chernock RD, Wang X, Gao G, Lewis JS Jr, Zhang Q, Thorstad WL et al (2013) Detection and significance of human papillomavirus, CDKN2A(p16) and CDKN1A(p21) expression in squamous cell carcinoma of the larynx. Mod Pathol 26:223–231

    Article  PubMed  Google Scholar 

  24. Cho KJ, Su J, Kim SB, Lee SW, Choi SH, Nam SY et al (2017) Basaloid squamous cell carcinoma of the head and neck: subclassification into basal, ductal, and mixed subtypes based on comparison of clinico-pathologic features and expression of p53, cyclin D1, epidermal growth factor receptor, p16, and human papillomavirus. J Pathol Transl Med. https://doi.org/10.4132/jptm.2017.03.03

    Google Scholar 

  25. Begum S, Westra WH (2008) Basaloid squamous cell carcinoma of the head and neck is a mixed variant that can be further resolved by HPV status. Am J Surg Pathol 32:1044–1050

    Article  PubMed  Google Scholar 

  26. Baba Y, Ishimoto T, Harada K, Kosumi K, Murata A, Miyake K et al (2015) Molecular characteristics of basaloid squamous cell carcinoma of the esophagus: analysis of KRAS, BRAF, and PIK3CA mutations and LINE-1 methylation. Ann Surg Oncol 22:3659–3665

    Article  PubMed  Google Scholar 

  27. Imamhasan A, Mitomi H, Saito T, Hayashi T, Takahasi M, Kajiyama Y et al (2012) Immunohistochemical and oncogenetic analysis of the esophageal basaloid squamous cell carcinoma in comparison with conventional squamous cell carcinomas. Hum Pathol 43:2012–2023

    Article  PubMed  Google Scholar 

  28. Solomon MC, Vidyasagar MS, Fernandes D, Guddattu V, Mathew M, Shergill AK et al (2016) The prognostic implication of the expression of EGFR, p53, cyclin D1, Bcl-2 and p16 in primary locally advanced oral squamous cell carcinoma cases: a tissue microarray study. Med Oncol 33:138

    Article  PubMed  Google Scholar 

  29. Gonzalez JC, Cepeda LG, Yanez SB, Cornejo A, Estevez AM, Huerta E (2016) p53 and p16 in oral epithelial dysplasia and oral squamous cell carcinoma: a study of 208 cases. Indian J Pathol Microbiol 59:153–158

    Article  Google Scholar 

  30. Rodríguez Tojo MJ, García Cano FJ, Infante Sánchez JC, Velázquez Fernández E, Aguirre Urízar JM (2005) Immunoexpression of p53, Ki-67, and E-cadherin in basaloid squamous cell carcinoma of the larynx. Clin Transl Oncol 7:110–114

    Article  PubMed  Google Scholar 

  31. Nylander K, Dabelsteen E, Hall PA (2000) The p53 molecule and its prognostic role in squamous cell carcinoma of the head and neck. J Oral Pathol Med 29:413–425

    Article  PubMed  Google Scholar 

  32. Cohen ER, Reis IM, Gomez C, Pereira L, Freiser ME, Hoosien G et al (2017) Immunohistochemistry analysis of CD44, EGFR, and p16 in oral cavity and oropharyngeal squamous cell carcinoma. Otolaryngol Head Neck Surg. https://doi.org/10.1177/0194599817700371

    PubMed Central  Google Scholar 

  33. Begum S, Gillison ML, Ansari-Lari MA, Shah K, Westra WH (2003) Detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin. Clin Cancer Res 9(17):6469–6475

    PubMed  Google Scholar 

  34. Klaes R, Friedrich T, Spitkovsky D, Ridder R, Rudy W, Petry U et al (2001) Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer 92(2):276–284

    Article  PubMed  Google Scholar 

  35. Sano T, Oyama T, Kashiwabara K, Fukuda T, Nakajima T (1998) Expression status of p16 protein is associated with human papillomavirus oncogenic potential in cervical and genital lesions. Am J Pathol 153(6):1741–1748

    Article  PubMed  PubMed Central  Google Scholar 

  36. Gröbe A, Hanken H, Kluwe L, Schöllchen M, Tribius S, Pohlenz P et al (2013) Immunohistochemical analysis of p16 expression, HPV infection and its prognostic utility of oral squamous cell carcinoma. J Oral Pathol Med 42:676–681

    Article  PubMed  Google Scholar 

  37. Friederich RE, Sperber C, Jäkel T, Röser K, Löning T (2010) Basaloid lesions of oral squamous epithelial cells and their association with HPV infection and P16 expression. Anticancer Res 30:1605–1612

    Google Scholar 

  38. Chung CH, Gillison ML (2009) Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res 15:6758–6762

    Article  PubMed  Google Scholar 

  39. Sedghizadeh PP, Billington WD, Paxton D, Ebeed R, Mahabady S, Clark GT et al (2016) Is p16-positive oropharyngeal squamous cell carcinoma associated with favorable prognosis? A systematic review and meta-analysis. Oral Oncol 54:15–27

    Article  PubMed  Google Scholar 

  40. Sritippho T, Pongsiriwet S, Lertprasertsuke N, Buddhachat K, Sastraruji T, Iamaroon A (2016) p16—a possible surrogate marker for high-risk human papillomaviruses in oral cancer? Asian Pac J Cancer Prev 17:4049–4057

    PubMed  Google Scholar 

  41. Upile NS, Shaw RJ, Jones TM, Goodyear P, Liloglou T, Risk JM et al (2014) Squamous cell carcinoma of the head and neck outside the oropharynx is rarely human papillomavirus related. Laryngoscope 124(12):2739–2744

    Article  PubMed  Google Scholar 

  42. Ambrosch P, Schlott T, Hilmes D, Ruschenburg I (2001) p16 alterations and retinoblastoma protein expression in squamous cell carcinoma and neighboring dysplasia from the upper aerodigestive tract. Virchows Arch 438:343–349

    Article  PubMed  Google Scholar 

  43. Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM et al (2002) A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109:335–346

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the Foundation for Research Support in the State of Goiás for the financial support (FAPEG Grant No. 201201270020063).

Funding

Financial support was provided by the Foundation for Research Support in the State of Goiás (FAPEG Grant No. 201201270020063).

Author information

Authors and Affiliations

  1. Department of Stomatologic Sciences, Oral Pathology, Federal University of Goiás, Praça Universitária s/n, Setor Universitário, Goiânia, GO, 74605-220, Brazil

    Allisson Filipe Lopes Martins, Marília Oliveira Morais, Aline Carvalho Batista & Elismauro Francisco Mendonça

  2. Araujo Jorge Cancer Hospital, Rua 239, n 206, Setor Universitário, Goiânia, GO, 74175-120, Brazil

    Carlos Henrique Pereira

  3. Department of Bucomaxilofacial Surgery of Clinics Hospital, Federal University of Goiás, Praça Universitária s/n, Setor Universitário, Goiânia, GO, 74605-220, Brazil

    Lucas Borges Fleury Fernandes

  4. Endodontic Departament, Federal University of Goiás, Praça Universitária s/n, Setor Universitário, Goiânia, GO, 74605-220, Brazil

    Paulo Otávio Carmo Souza

Authors
  1. Allisson Filipe Lopes Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos Henrique Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marília Oliveira Morais
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paulo Otávio Carmo Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lucas Borges Fleury Fernandes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aline Carvalho Batista
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Elismauro Francisco Mendonça
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elismauro Francisco Mendonça.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Informed consent

Due to the retrospective nature of this study, formal consent of each participant was not required.

Ethical approval

This research was approved by the Federal University of Goiás Research Ethics Committee (Protocol 22/2013).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Martins, A.F.L., Pereira, C.H., Morais, M.O. et al. p53 and p16 expression in oral cavity squamous cell and basaloid squamous cell carcinoma. Oral Cancer 2, 7–17 (2018). https://doi.org/10.1007/s41548-018-0004-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41548-018-0004-1

Keywords

Search

Navigation