Abstract
It is of great clinical importance to identify simple prognostic markers from preoperative biopsies that could guide treatment planning. Here, we compared tumor budding (B), depth of invasion (D), and the combined scores (i.e., budding and depth of invasion (BD) histopathologic model) in preoperative biopsies and the corresponding postoperative specimens of oral tongue squamous cell carcinoma (OTSCC). Tumor budding and depth of invasion were evaluated in the pre- and postoperative samples from 100 patients treated for OTSCC. Sensitivity and specificity statistics were used. Our results showed statistically significant (P < 0.001) relationship between pre- and postoperative BD scores. There was an agreement between the pre- and postoperative BD model scores in 83 cases (83%) with 57.1% sensitivity (95% CI 39.4 to 73.7%) and 96.9% specificity (95% CI 89.3 to 99.6%). Our findings suggest that the BD model, analyzed from representative biopsies, could be used for the treatment planning of OTSCC.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs00428-017-2212-1/MediaObjects/428_2017_2212_Fig1_HTML.gif)
Similar content being viewed by others
References
Ng JH, Iyer NG, Tan MH, Edgren G (2016) Changing epidemiology of oral squamous cell carcinoma of the tongue: a global study. Head Neck. doi:10.1002/hed.24589
Almangush A, Bello IO, Coletta RD, Makitie AA, Makinen LK, Kauppila JH, Pukkila M, Hagstrom J, Laranne J, Soini Y, Kosma VM, Koivunen P, Kelner N, Kowalski LP, Grenman R, Leivo I, Laara E, Salo T (2015) For early-stage oral tongue cancer, depth of invasion and worst pattern of invasion are the strongest pathological predictors for locoregional recurrence and mortality. Virchows Arch 467:39–46. doi:10.1007/s00428-015-1758-z
Ganly I, Patel S, Shah J (2012) Early stage squamous cell cancer of the oral tongue—clinicopathologic features affecting outcome. Cancer 118:101–111. doi:10.1002/cncr.26229
Almangush A, Coletta RD, Bello IO, Bitu C, Keski-Santti H, Makinen LK, Kauppila JH, Pukkila M, Hagstrom J, Laranne J, Tommola S, Soini Y, Kosma VM, Koivunen P, Kowalski LP, Nieminen P, Grenman R, Leivo I, Salo T (2015) A simple novel prognostic model for early stage oral tongue cancer. Int J Oral Maxillofac Surg 44:143–150. doi:10.1016/j.ijom.2014.10.004
Sawazaki-Calone I, Rangel A, Bueno AG, Morais CF, Nagai HM, Kunz RP, Souza RL, Rutkauskis L, Salo T, Almangush A, Coletta RD (2015) The prognostic value of histopathological grading systems in oral squamous cell carcinomas. Oral Dis 21:755–761. doi:10.1111/odi.12343
Strieder L, Coutinho-Camillo CM, Costa V, da Cruz Perez DE, Kowalski LP, Kaminagakura E (2017) Comparative analysis of three histologic grading methods for squamous cell carcinoma of the lip. Oral Dis 23:120–125. doi:10.1111/odi.12586
Barnes LEJ, Reichart P, Sidransky D (2005) World Health Organization classification of tumors. Pathology and genetics of head and neck tumours. IARC Press, Lyon
Bryne M, Koppang HS, Lilleng R, Kjaerheim A (1992) Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol 166:375–381. doi:10.1002/path.1711660409
Brandwein-Gensler M, Teixeira MS, Lewis CM, Lee B, Rolnitzky L, Hille JJ, Genden E, Urken ML, Wang BY (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 29:167–178
Almangush A, Salo T, Hagstrom J, Leivo I (2014) Tumour budding in head and neck squamous cell carcinoma—a systematic review. Histopathology 65:587–594. doi:10.1111/his.12471
Almangush A, Karhunen M, Hautaniemi S, Salo T, Leivo I (2016) Prognostic value of tumour budding in oesophageal cancer: a meta-analysis. Histopathology 68:173–182. doi:10.1111/his.12781
Rogers AC, Winter DC, Heeney A, Gibbons D, Lugli A, Puppa G, Sheahan K (2016) Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer. Br J Cancer 115:831–840. doi:10.1038/bjc.2016.274
Karamitopoulou E (2012) Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer. Front Oncol 2:209. doi:10.3389/fonc.2012.00209
Kadota K, Nitadori J, Woo KM, Sima CS, Finley DJ, Rusch VW, Adusumilli PS, Travis WD (2014) Comprehensive pathological analyses in lung squamous cell carcinoma: single cell invasion, nuclear diameter, and tumor budding are independent prognostic factors for worse outcomes. J Thorac Oncol 9:1126–1139. doi:10.1097/JTO.0000000000000253
Gujam FJ, McMillan DC, Mohammed ZM, Edwards J, Going JJ (2015) The relationship between tumour budding, the tumour microenvironment and survival in patients with invasive ductal breast cancer. Br J Cancer 113:1066–1074. doi:10.1038/bjc.2015.287
Xie N, Wang C, Liu X, Li R, Hou J, Chen X, Huang H (2015) Tumor budding correlates with occult cervical lymph node metastasis and poor prognosis in clinical early-stage tongue squamous cell carcinoma. J Oral Pathol Med 44:266–272. doi:10.1111/jop.12242
Almangush A, Bello IO, Keski-Santti H, Makinen LK, Kauppila JH, Pukkila M, Hagstrom J, Laranne J, Tommola S, Nieminen O, Soini Y, Kosma VM, Koivunen P, Grenman R, Leivo I, Salo T (2014) Depth of invasion, tumor budding, and worst pattern of invasion: prognostic indicators in early-stage oral tongue cancer. Head Neck 36:811–818. doi:10.1002/hed.23380
Seki M, Sano T, Yokoo S, Oyama T (2016) Histologic assessment of tumor budding in preoperative biopsies to predict nodal metastasis in squamous cell carcinoma of the tongue and floor of the mouth. Head Neck 38(Suppl 1):E1582–E1590. doi:10.1002/hed.24282
Piazza C, Montalto N, Paderno A, Taglietti V, Nicolai P (2014) Is it time to incorporate ‘depth of infiltration’ in the T staging of oral tongue and floor of mouth cancer? Curr Opin Otolaryngol Head Neck Surg 22:81–89. doi:10.1097/MOO.0000000000000038
Krakhmal NV, Zavyalova MV, Denisov EV, Vtorushin SV, Perelmuter VM (2015) Cancer invasion: patterns and mechanisms. Acta Nat 7:17–28
Brandwein-Gensler M, Smith RV, Wang B, Penner C, Theilken A, Broughel D, Schiff B, Owen RP, Smith J, Sarta C, Hebert T, Nason R, Ramer M, DeLacure M, Hirsch D, Myssiorek D, Heller K, Prystowsky M, Schlecht NF, Negassa A (2010) Validation of the histologic risk model in a new cohort of patients with head and neck squamous cell carcinoma. Am J Surg Pathol 34:676–688. doi:10.1097/PAS.0b013e3181d95c37
Ueno H, Mochizuki H, Shinto E, Hashiguchi Y, Hase K, Talbot IC (2002) Histologic indices in biopsy specimens for estimating the probability of extended local spread in patients with rectal carcinoma. Cancer 94:2882–2891. doi:10.1002/cncr.10551
Wang C, Huang H, Huang Z, Wang A, Chen X, Huang L, Zhou X, Liu X (2011) Tumor budding correlates with poor prognosis and epithelial-mesenchymal transition in tongue squamous cell carcinoma. J Oral Pathol Med 40:545–551. doi:10.1111/j.1600-0714.2011.01041.x
Attramadal CG, Kumar S, Boysen ME, Dhakal HP, Nesland JM, Bryne M (2015) Tumor budding, EMT and cancer stem cells in T1–2/N0 oral squamous cell carcinomas. Anticancer Res 35:6111–6120
Hori Y, Kubota A, Yokose T, Furukawa M, Matsushita T, Takita M, Mitsunaga S, Mizoguchi N, Nonaka T, Nakayama Y, Oridate N (2017) Predictive significance of tumor depth and budding for late lymph node metastases in patients with clinical N0 early oral tongue carcinoma. Head Neck Pathol. doi:10.1007/s12105-017-0814-1
Nakagawa Y, Ohira M, Kubo N, Yamashita Y, Sakurai K, Toyokawa T, Tanaka H, Muguruma K, Shibutani M, Yamazoe S, Kimura K, Nagahara H, Amano R, Ohtani H, Yashiro M, Maeda K, Hirakawa K (2013) Tumor budding and E-cadherin expression are useful predictors of nodal involvement in T1 esophageal squamous cell carcinoma. Anticancer Res 33:5023–5029
Luo WR, Gao F, Li SY, Yao KT (2012) Tumour budding and the expression of cancer stem cell marker aldehyde dehydrogenase 1 in nasopharyngeal carcinoma. Histopathology 61:1072–1081. doi:10.1111/j.1365-2559.2012.04350.x
Tan WJ, Chia CS, Tan HK, Soo KC, Iyer NG (2012) Prognostic significance of invasion depth in oral tongue squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec 74:264–270. doi:10.1159/000343796
Jung J, Cho NH, Kim J, Choi EC, Lee SY, Byeon HK, Park YM, Yang WS, Kim SH (2009) Significant invasion depth of early oral tongue cancer originated from the lateral border to predict regional metastases and prognosis. Int J Oral Maxillofac Surg 38:653–660. doi:10.1016/j.ijom.2009.01.004
Ganly I, Goldstein D, Carlson DL, Patel SG, O'Sullivan B, Lee N, Gullane P, Shah JP (2013) Long-term regional control and survival in patients with “low-risk,” early stage oral tongue cancer managed by partial glossectomy and neck dissection without postoperative radiation: the importance of tumor thickness. Cancer 119:1168–1176. doi:10.1002/cncr.27872
Han MW, Lee JC, Kim YM, Cha HJ, Roh JL, Choi SH, Nam SY, Cho KJ, Kim SW, Kim SY (2015) Epithelial-mesenchymal transition: clinical implications for nodal metastasis and prognosis of tongue cancer. Otolaryngol Head Neck Surg 152:80–86. doi:10.1177/0194599814556061
Huang SH, Hwang D, Lockwood G, Goldstein DP, O'Sullivan B (2009) Predictive value of tumor thickness for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity: a meta-analysis of reported studies. Cancer 115:1489–1497. doi:10.1002/cncr.24161
Goel V, Parihar PS, Parihar A, Goel AK, Waghwani K, Gupta R, Bhutekar U (2016) Accuracy of MRI in prediction of tumour thickness and nodal stage in oral tongue and gingivobuccal cancer with clinical correlation and staging. J Clin Diagn Res 10:TC01–TC05. doi:10.7860/JCDR/2016/17411.7905
Lodder WL, Teertstra HJ, Tan IB, Pameijer FA, Smeele LE, van Velthuysen ML, van den Brekel MW (2011) Tumour thickness in oral cancer using an intra-oral ultrasound probe. Eur Radiol 21:98–106. doi:10.1007/s00330-010-1891-7
Mark Taylor S, Drover C, Maceachern R, Bullock M, Hart R, Psooy B, Trites J (2010) Is preoperative ultrasonography accurate in measuring tumor thickness and predicting the incidence of cervical metastasis in oral cancer? Oral Oncol 46:38–41. doi:10.1016/j.oraloncology.2009.10.005
Preda L, Chiesa F, Calabrese L, Latronico A, Bruschini R, Leon ME, Renne G, Bellomi M (2006) Relationship between histologic thickness of tongue carcinoma and thickness estimated from preoperative MRI. Eur Radiol 16:2242–2248. doi:10.1007/s00330-006-0263-9
S Kumar S GN, Anila K R, Sebastian P. (2015) Can frozen section be used to assess depth of invasion of early carcinoma of tongue? Oral Oncol 51:e87–e88
Lydiatt WM, Patel SG, O'Sullivan B, Brandwein MS, Ridge JA, Migliacci JC, Loomis AM, Shah JP (2017) Head and neck cancers—major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin 67:122–137. doi:10.3322/caac.21389
Sgaramella N, Coates PJ, Strindlund K, Loljung L, Colella G, Laurell G, Rossiello R, Muzio LL, Loizou C, Tartaro G, Olofsson K, Danielsson K, Fahraeus R, Nylander K (2015) Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1. Br J Cancer 113:321–326. doi:10.1038/bjc.2015.207
Kang H, Kiess A, Chung CH (2015) Emerging biomarkers in head and neck cancer in the era of genomics. Nat Rev Clin Oncol 12:11–26. doi:10.1038/nrclinonc.2014.192
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Institutional review board approval was obtained from the ethics committees of Helsinki, Kuopio, and Oulu University Hospitals.
Funding
This study was supported by the Finnish Dental Society (Alhadi Almangush), the Maritza and Reino Salonen Foundation (Ilmo Leivo), and the Finnish Cancer Society (Tuula Salo).
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Almangush, A., Leivo, I., Siponen, M. et al. Evaluation of the budding and depth of invasion (BD) model in oral tongue cancer biopsies. Virchows Arch 472, 231–236 (2018). https://doi.org/10.1007/s00428-017-2212-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-017-2212-1