Tumor budding and depth of invasion can be used as prognostic risk factors in determining treatment plan for early stage oral squamous cell carcinoma

Kaduganoor Ramakrishnan Mohan, Rahamathulla Mudassar Sharief, Rahila C.


Background: The grading of oral squamous cell carcinoma can be useful along with TNM staging in determining treatment plan. The aim is to evaluate the prognostic value of histopathological grading of oral squamous cell carcinoma and to find its importance in setting appropriate treatment plan.

Methods: The study includes 60 oral squamous cell carcinoma cases surgically operated during January 2012 to December 2018. From the archival paraffin blocks and available resected specimens of each case, the histological parameters used in Bryne’s invasive grading system and Almangush BD model were evaluated and compared to their prognosis.

Results: The parameters used in BD model-tumor budding and depth of invasion were found to be statistically significant with prognosis of the disease. Except for nuclear polymorphism, the parameters used in Bryne’s invasive front grading system do not correlate with prognosis.

Conclusion: Based on the prognostic significance, tumor budding ≥5 buds in the invasive front area and depth of invasion ≥4mm can be used as risk factors in prospective clinical trials by considering them in early stage disparity cases for multimodality treatment approach and elective neck dissection.


Depth of invasion, Elective neck dissection, Histopathological parameters, Oral squamous cell carcinoma, Tumor budding

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Dissanayaka WL, Pitiyage G, Kumarasiri PVR, Liyanage RLPR, Dias KD, TIlakaratne WM. Clinical and histopathologic parameters in survival of oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113(4):518-25.

Broders AC. Squamous cell carcinoma of the lip: a study of five hundred and thirty-seven cases. JAMA 1920;74(10):656-64.

Anneroth G, Batsakis J, Luna M. Review of the literature and a recommended system of malignancy grading in oral squamous cell carcinomas. Scand J Dent Res. 1987;95(3):229-49.

Bryne M, Koppang HS, Lilleng R, Kjaerheim A. Malignancy grading of deep invasive margins of oral squamous cell carcinoma. L Pathol. 1992;166(4):375-81.

Bryne M, Koppang HS, Lilleng R, Stene T, Bang G, New DE. New malignancy grading is a better prognostic indicator than Borders grading in oral squamous cell carcinoma. J Oral Pathol Med 1989;18(8):432-37.

Brandwein-Gensler M, Smith RV, Wang B, Penner C, Theiken A, Broughel D, et al. Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma. Am J Surg Pathol. 2010;34(5):676-88.

Almangush A, Coletta RD, Bello IO, Keski-Santti H, Makinen LK, Kauppila JH, et al. A simple novel prognostic model for early-stage oral tongue cancer. Int J Oral Maxillofac Surg. 2015;44(2):143-50.

Sawazaki-Calone I, Rangel ALCA, Bueno AG, Morais CF, Nagai HM, Kunz RP et al. The prognostic value of the histological grading systems in oral squamous cell carcinoma. Oral Disease 2015; 21(6):755-61.

Upul Dissanayake. Malignancy grading of invasive front of oral squamous cell carcinoma: correlation with overall survival. Translational Research in Oral Oncol. 2017;2:1-8.

Anneroth G, Batsakis J, Luna M. Review of the literature and a recommended system of malignancy grading in oral squamous cell carcinomas. Scand J Dent Res. 1987;95(3):229-49.

Juliana-Cristina Frare, Iris Swazaki-calone, Ayroza-Rangel AL, Galvao Bueno A, Carlo-Floriano, Nagai HM, et al. Histopathological grading systems analysis of oral squamous cell carcinomas of young patients. Med Oral Pathol Oral Cir Buccal May 1; 2016;21(3): e285-98.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Head and Neck Cancers [Internet]. NCCN. org. Version 1.2019. Available at: Accessed 5 February 2019.

Akther M, Hossain S, Rahman QB, Molla MR. A study in histological grading of oral squamous cell carcinoma as its co-relationship with regional metastasis. J Oral Maxillofac Pathol. 2011;15(2):168-76.

Larsen SR, Johansen J, Sorensen A, Krogdahl A. The prognostic significance of histological features in oral squamous cell carcinoma. J Oral Pathol Med 2009; 38(8):657-62.

Mohit-Tabatabai MA, Sobel HJ, Rush BF, Mashberg A. Relation of thickness of floor of mouth stage I and II cancers to regional metastasis. Am J Surg. 1986;152(4):351-3.

O’Brien CJ, Lauer CS, Fredricks S, Clifford AR, McNeil EB, Bagia JS et al. Tumor thickenss influences prognosis of T1 and T2 oral cavity cancer- but what thickness? Head and Neck 2003;25:937-45.

Wang C, Huang H, Huang Z, Wang A, Chen X, Huang L et al. Tumor budding correlates with poor prognosis and epithelial-mesenchymal transition in tongue squamous cell carcinoma. J Oral Pathol Med 2001; 40(7):545-51.

Costa Ade L, Araujo Junior RF, Ramos CC. Correlation between TNM classification and malignancy histological features of oral squamous cell carcinoma. Braz J Otorhinolaryngol Mar-Apr 2005;71 (2):181-7.

Johannes Betge, Peter Kornprat, Marion J Pollheomer, Lindtner RA, Schlemmer A, Rehak P et al. Tumor budding is an independent predictor of outcome in AJCC/UICC Stage II colorectal Cancer. Ann Surg Oncol. 2012; 19(12):3706-12.

Huang SH, Hwang D, Lockwood G, MMath, Goldstein D, O’Sullivan B. Predictive value of tumor thickness for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity. Cancer. April 1 2009; 1489-97.

Kane SV, Guptha M, Kakade AC, D’Cruz. Depth of invasion is the most significant histological predictor of subclinical lymph node metastasis in early squamous carcinomas of the oral cavity. Eur J Surg Oncol. 2006;32(7):795-803.

Moore C, Kuhns JG, Greenberg RA. Thickness as prognostic aid in upper aerodigestive tract cancer. Arch Surg. 1986;121(12):1410-14.

Kurokawa H, Yamashita Y, Takeda S, Zhang M, Fukuyama H, Takahashi T. Risk factors for late cervical lymph node metastasis in patients with stage I or II carcinoma of the tongue. Head Neck. 2002;24(8):731-36.

Amin MB, Edge SB, Green F, Byrd DR, Brookland RK, Washington MK, et al. American Joint Committee on Cancer. AJCC Cancer Staging Manual. 8th edition. New York, NY: Springer; 2017. Available at:

Masood MM, Farquhar DR, Vanleer JP, Patel SN, Hackman TG. Depth of invasion on pathological outcomes in clinical oral tongue cancer patients. Oral Dis. 2018;24(7):1198-203.

Almangush A, Perinen M, Heikkien I, Makitie AA, Salo T, Leivo I. Tumor budding in oral squamous cell carcinoma: a meta-analysis. British J Cancer. 2018;118:577-86.

Pedersen NJ, Jensen DH, Lelkaitis G, Kiss K, Charabi B, Specht L, et al. Construction of a pathological risk model of occult lymph node metastases for prognostication by semi-automated image analysis of tumor budding in early-stage oral squamous cell carcinoma. Oncotarget, 2017;8(11): 18227-37.

Rogers AC, Winter DC, Heeney A et al. Systematic review and meta-analysis of the impact of tumor budding in colorectal cancer. Br J Cancer 2016; 115(7): 831-40.

Kadota K, Yeh YC, Villena-Vargas J, Cherkassky L, Drill EN, Sima S, et al. Tumor budding correlates with the protumor immune microenvironment and is an independent prognostic factor for recurrence of stage I lung adenocarcinoma. Chest. 2015;148(3): 711-21.

Gujam FJ, McMillan DC, Mohammed ZM, Edwards J, Going JJ. The relationship between tumour budding, the tumour microenvironment and survival in patients with invasive ductal breast cancer. Br J Cancer. 2015;113(7):1066-74.