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Incorporating the epidermal growth factor receptor expression and histopathological parameters in a mathematical model to predict the prognosis of oral squamous cell carcinoma: a prospective observational cohort study

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Abstract

Background

Oral squamous cell carcinomas (OSCC) are the most common type of variant causing oral cancers, contributing for around 90%. The overall survival of these patients is below 50%. The postoperative overall survival (OS) has not improved over years much despite of advanced surgical techniques and invention of various anticancer drugs. There was always a requirement for a non-invasive molecular marker to predict the prognosis of these patients. The epidermal growth factor and their receptors are not only thought to play a critical but also an influential role in growth of the cell and differentiation in normal/ healthy tissues. They also play an important role in malignant progression of disease and tumorigenesis. A better and sound understanding of mechanisms at molecular level and identification of potential oncogenes in OSCC may provide innovative therapeutic decisions such as targeted therapy in management of these cancer patients.

Aim & objectives

The aim of this study is to check whether epidermal growth factor expression is a prognosticator in oral squamous cell carcinoma and also to propose a mathematical model to find the prognosis of the patients which have not been done so far in the literature.

Materials & methods

The study was a prospective cohort study with 25 patients who had biopsy proven OSCC who reported to our hospital from July 2017 to June 2019. The data collected from their histopathological report for this prospective study and model were: surgical margins (superior, inferior, anterior and posterior), depth of tumor, lymph nodal metastasis, lymphovascular invasion and scoring of epidermal growth factor receptor (EGFR) expression done by immunohistochemistry (IHC) on wax blocks.

Results

EGFR expression on surgical margins was found to have a p-value of 0.023 which was significant statistically. EGFR expression showed a statistically significant p value 0.002 as independent marker in prognosis with sensitivity of 97.7% and specificity of 61.2%. The tumor depth of infiltration showed an insignificant correlation with pathological Tumor, Node, Metastasis (TNM) staging with a p value of 0.860. A mathematical model linear regression equation was proposed which predicted a cutoff value above 16, the prognosis of the patient being bad (Stages III and IV), and below 16, the prognosis of the patient being good (Stages I and II).

Conclusion

This study put forward a proposed mathematical model by incorporating all important parameters to predict the prognosis of the patients. EGFR expression is one such important parameter to be considered to develop anti-EGFR agents to improve the OS of the patients.

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References

  1. Arteaga C (2003) Targeting HER1/EGFR: a molecular approach to cancer therapy. Semin Oncol 30(Suppl 7):3–14

    Article  CAS  Google Scholar 

  2. Baselga J (2001) Targeting the epidermal growth factor receptor: a clinical reality. J Clin Oncol 19(Suppl):41S-44S

    CAS  Google Scholar 

  3. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578

    Article  CAS  Google Scholar 

  4. Cohen S, Carpenter G, King L Jr (1980) Epidermal growth factorreceptor- protein kinase interactions: co-purification of receptor and epidermal growth factor-enhanced phosphorylation activity. J Biol Chem 255:4834–4842

    Article  CAS  Google Scholar 

  5. Reimers N, Kasper HU, Weissenborn SJ, Stützer H, Preuss SF, Hoffmann TK et al (2007) Combined analysis of HPV-DNA, p16 and EGFR expression to predict prognosis in oropharyngeal cancer. Int J Cancer 120(8):1731–1738

    Article  CAS  Google Scholar 

  6. Albitar L, Pickett G, Morgan M, Wilken JA, Maihle NJ, Leslie KK (2010) EGFR isoforms and gene regulation in human endometrial cancer cells. Mol Cancer 9:166

    Article  Google Scholar 

  7. Mehta A, Chowdhary M, Sinha R (2015) Immunoscoring of epidermal growth factor receptor expression in recurrent cases of oral squamous cell carcinoma. J Oral Pathol Med 44(10):818–822

    Article  CAS  Google Scholar 

  8. Hama T, Yuza Y, Saito Y, O-uchi J, Kondo S, Okabe M et al (2009) Prognostic significance of epidermal growth factor receptor phosphorylation and mutation in head and neck squamous cell carcinoma. Oncologist 14(9):900–908

    Article  CAS  Google Scholar 

  9. Sessions DG, Spector GJ, Lenox J, Haughey B, Chao C, Marks J (2002) Analysis of treatment results for oral tongue cancer. Laryngoscope 112:616–625

    Article  Google Scholar 

  10. Ayazi B, Saleem K, Azim W, Shaikh A (2011) A clinicopathological study of oral cancers. Biomedica 27:29–32

    Google Scholar 

  11. Chen PH, Shieh TY, Ho PS, Tsai CC, Yang YH, Lin YC et al (2007) Prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan. BMC Cancer 7:101

    Article  CAS  Google Scholar 

  12. Binmadi NO, Basile JR (2011) Perineural invasion in oral squamous cell carcinoma: a discussion of significance and review of the literature. Oral Oncol 47:1005–1010

    Article  Google Scholar 

  13. Rapidis AD, Givalos N, Gakiopoulou H, Faratzis G, Stavrianos SD, Vilos GA et al (2005) Adenoid cystic carcinoma of the head and neck. Clinicopathological analysis of 23 patients and review of the literature. Oral Oncol 41:328–35

    Article  Google Scholar 

  14. Nair D, Mair M, Singhvi H, Mishra A, Nair S, Agrawal J, Chaturvedi P (2018) Perineural invasion: independent prognostic factor in oral cancer that warrants adjuvant treatment. Head Neck 40(8):1780–1787

    Google Scholar 

  15. Adel M, Kao HK, Hsu CL, Huang JJ, Lee LY, Huang Y, Browne T et al (2015) Evaluation of lymphatic and vascular invasion in relation to clinicopathological factors and treatment outcome in oral cavity squamous cell carcinoma. Medicine 94(43):e1510

    Article  Google Scholar 

  16. Jakobsson PÅ, Eneroth CM, Killander D, Moberger G, Mårtensson B (1973) Histologic classification and grading of malignancy in carcinoma of the larynx. Acta Radiol Ther Phys Biol 12(1):1–8

    Article  CAS  Google Scholar 

  17. Jones HB, Sykes A, Bayman N, Sloan P, Swindell R, Patel M, Musgrove B (2009) The impact of lymphovascular invasion on survival in oral carcinoma. Oral Oncol 45(1):10–15

    Article  CAS  Google Scholar 

  18. Oliveira LR, Ribeiro-Silva A (2011) Prognostic significance of immunohistochemical biomarkers in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 40(3):298–307

    Article  CAS  Google Scholar 

  19. Sarkis SA, Abdullah BH, Majeed BA, Talabani NG (2010) Immunohistochemical expression of epidermal growth factor receptor (EGFR) in oral squamous cell carcinoma in relation to proliferation, apoptosis, angiogenesis and lymphangiogenesis. Head Neck Oncol 2(1):1–8

    Article  Google Scholar 

  20. Baba Y, Fujii M, Tokumaru Y, Kato Y (2012) Present and future of EGFR inhibitors for head and neck squamous cell cancer. J Oncol 1:2012

    Google Scholar 

  21. Rahima B, Shingaki S, Nagata M, Saito C (2004) Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 97(4):423–431

    Article  Google Scholar 

  22. Zanotti L, Paderno A, Piazza C, Pagan E, Bignotti E, Romani C et al (2017) Epidermal growth factor receptor detection in serum and saliva as a diagnostic and prognostic tool in oral cancer. Laryngoscope 127(11):E408–E414

    Article  CAS  Google Scholar 

  23. Hashmi AA, Hussain ZF, Aijaz S, Irfan M, Khan EY, Naz S et al (2018) Immunohistochemical expression of epidermal growth factor receptor (EGFR) in South Asian head and neck squamous cell carcinoma: association with various risk factors and clinico-pathologic and prognostic parameters. World J Surg Oncol 16(1):1–9

    Article  Google Scholar 

  24. Akheel M, George RK, Jain A, Chahwala Q, Wadhwania A (2019) Surgical margins and nodal metastasis are prognostic factors in oral squamous cell carcinoma: a meta-analysis. Clin Cancer Investig J 8(2):47

    Google Scholar 

  25. Brandwein-Gensler M, Teixeira MS, Lewis CM, Lee B, Rolnitzky L, Hille JJ et al (2005) Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol 29(2):167–178

    Article  Google Scholar 

  26. Srinivasan M, Jewell SD (2001) Evaluation of TGF-α and EGFR expression in oral leukoplakia and oral submucous fibrosis by quantitative immunohistochemistry. Oncology 61(4):284–292

    Article  CAS  Google Scholar 

  27. Ang KK, Berkey BA, Tu X, Zhang HZ, Katz R, Hammond EH, Fu KK, Milas L (2002) Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Can Res 62(24):7350–7356

    CAS  Google Scholar 

  28. Lee JW, Soung YH, Kim SY, Nam HK, Park WS, Nam SW et al (2005) Somatic mutations of EGFR gene in squamous cell carcinoma of the head and neck. Clin Cancer Res 11(8):2879–2882

    Article  CAS  Google Scholar 

  29. Chung CH, Ely K, McGavran L, Varella-Garcia M, Parker J, Parker N et al (2006) Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol 24(25):4170–4176

    Article  CAS  Google Scholar 

  30. Loree TR, Strong EW (1990) Significance of positive margins in oral cavity squamous carcinoma. Am J Surg 160(4):410–414

    Article  CAS  Google Scholar 

  31. Mistry RC, Qureshi SS, Kumaran C (2005) Post-resection mucosal margin shrinkage in oral cancer: quantification and significance. J Surg Oncol 91(2):131–133

    Article  Google Scholar 

  32. Cheng A, Cox D, Schmidt BL (2008) Oral squamous cell carcinoma margin discrepancy after resection and pathologic processing. J Oral Maxillofac Surg 66(3):523–529

    Article  Google Scholar 

  33. Helliwell T, Woolgar J (2011) Dataset for histopathology reporting of mucosal malignancies of the oral cavity. Royal College of Pathologists, London

    Google Scholar 

  34. Keski-Säntti H, Atula T, Törnwall J, Koivunen P, Mäkitie A (2006) Elective neck treatment versus observation in patients with T1/T2 N0 squamous cell carcinoma of oral tongue. Oral Oncol 42(1):95–100

    Article  Google Scholar 

  35. Melchers LJ, Schuuring E, van Dijk BA, De Bock GH, Witjes MJ, Van der Laan BF et al (2012) Tumour infiltration depth⩾ 4 mm is an indication for an elective neck dissection in pT1cN0 oral squamous cell carcinoma. Oral Oncol 48(4):337–42

    Article  CAS  Google Scholar 

  36. Balasubramanian D, Ebrahimi A, Gupta R, Gao K, Elliott M, Palme CE, Clark JR (2014) Tumour thickness as a predictor of nodal metastases in oral cancer: comparison between tongue and floor of mouth subsites. Oral Oncol 50(12):1165–1168

    Article  Google Scholar 

  37. Süslü N, Hoşal AŞ, Aslan T, Sözeri B, Dolgun A (2013) Carcinoma of the oral tongue: a case series analysis of prognostic factors and surgical outcomes. J Oral Maxillofac Surg 71(7):1283–1290

    Article  Google Scholar 

  38. Nuratna IN, Wisesa IB (2016) Association of Epidermal Growth Factor Receptor (EGFR) with tumor location and clinicopathological aspect in head and neck squamous cell carcinoma. Bali Med J 5(2):283–289

    Article  Google Scholar 

  39. Taberna M, Torres M, Alejo M, Mena M, Tous S, Marquez S, Pavón MA, León X, García J, Guix M, Hijano R, Bonfill T, Aguilà A, Lozano A, Mesía R, Alemany L, Bravo IG (2018) The use of HPV16-E5, EGFR, and pEGFR as prognostic biomarkers for oropharyngeal cancer patients. Front Oncol 11(8):589. https://doi.org/10.3389/fonc.2018.00589 (PMID:30619735;PMCID:PMC6297752.YenTC)

    Article  Google Scholar 

  40. Kaur G, Phogat D, Manu V (2021) Study of EGFR mutations in head and neck squamous cell carcinomas. Autops Case Rep 19:11

    Google Scholar 

  41. Liao CT, Chang JT, Wang HM, Ng SH, Hsueh C, Lee LY, Lin CH, Chen IH, Huang SF, Cheng AJ, Yen TC (2008) Analysis of risk factors of predictive local tumor control in oral cavity cancer. Ann Surg Oncol 15(3):915–22

    Article  Google Scholar 

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Authors and Affiliations

  1. Oral & Maxillofacial Surgery, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India

    Mohammad Akheel

  2. Dept of Oral Oncology, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India

    M. Senthilmurugan

  3. SRJ-CBCC Cancer Centre, Indore, India

    Amit Jain

  4. CHL Hospitals, Indore, India

    Qutubuddin Chahwala

  5. Dept of Pathology, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India

    Herald J. Sherlin

  6. Consultant Oral & Maxillofacial Surgeon, Indore, India

    Ashmi Wadhwania

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  1. Mohammad Akheel
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  2. M. Senthilmurugan
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  3. Amit Jain
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  4. Qutubuddin Chahwala
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  5. Herald J. Sherlin
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  6. Ashmi Wadhwania
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Contributions

Conception or design of the work was performed by MS and MA. Data collection was carried out by MA, AW, QC. Data analysis and interpretation were performed by MA, RG, HJS. Drafting the article is carried out by MA. Critical revision of the article was performed by MS and QC. Final approval of the version to be published was carried out by MA.

Corresponding author

Correspondence to Mohammad Akheel.

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The author declare that they have no conflicts of interest.

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Yes. The study involved 25 patients.

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Audio–visual consent and signed consents are taken from all patients participating in the study in English and local language (Hindi).

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Akheel, M., Senthilmurugan, M., Jain, A. et al. Incorporating the epidermal growth factor receptor expression and histopathological parameters in a mathematical model to predict the prognosis of oral squamous cell carcinoma: a prospective observational cohort study. J. Maxillofac. Oral Surg. 21, 1065–1073 (2022). https://doi.org/10.1007/s12663-022-01797-0

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