Skip to main content

Advertisement

SpringerLink
Log in

Evaluation of the budding and depth of invasion (BD) model in oral tongue cancer biopsies

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

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.

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

Similar content being viewed by others

References

  1. 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

  2. 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

    Article  PubMed  Google Scholar 

  3. 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

    Article  PubMed  Google Scholar 

  4. 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

    Article  CAS  PubMed  Google Scholar 

  5. 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

    Article  CAS  PubMed  Google Scholar 

  6. 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

    Article  CAS  PubMed  Google Scholar 

  7. Barnes LEJ, Reichart P, Sidransky D (2005) World Health Organization classification of tumors. Pathology and genetics of head and neck tumours. IARC Press, Lyon

    Google Scholar 

  8. 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

    Article  CAS  PubMed  Google Scholar 

  9. 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

    Article  PubMed  Google Scholar 

  10. 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

    Article  PubMed  Google Scholar 

  11. 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

    Article  PubMed  Google Scholar 

  12. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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

    PubMed  Google Scholar 

  14. 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

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 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

    Article  PubMed  Google Scholar 

  17. 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

    Article  PubMed  Google Scholar 

  18. 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

    Article  PubMed  Google Scholar 

  19. 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

    Article  PubMed  Google Scholar 

  20. Krakhmal NV, Zavyalova MV, Denisov EV, Vtorushin SV, Perelmuter VM (2015) Cancer invasion: patterns and mechanisms. Acta Nat 7:17–28

    CAS  Google Scholar 

  21. 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

    PubMed  Google Scholar 

  22. 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

    Article  PubMed  Google Scholar 

  23. 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

    Article  PubMed  PubMed Central  Google Scholar 

  24. 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

    CAS  PubMed  Google Scholar 

  25. 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

  26. 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

    PubMed  Google Scholar 

  27. 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

    Article  PubMed  Google Scholar 

  28. 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

    Article  PubMed  Google Scholar 

  29. 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

    Article  CAS  PubMed  Google Scholar 

  30. 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

    Article  PubMed  Google Scholar 

  31. 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

    Article  PubMed  Google Scholar 

  32. 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

    Article  CAS  PubMed  Google Scholar 

  33. 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

    PubMed  PubMed Central  Google Scholar 

  34. 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

    Article  PubMed  Google Scholar 

  35. 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

    Article  CAS  PubMed  Google Scholar 

  36. 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

    Article  PubMed  Google Scholar 

  37. 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

  38. 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

    Article  PubMed  Google Scholar 

  39. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 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

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Helsinki, Helsinki, Finland

    Alhadi Almangush

  2. Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki, Finland

    Alhadi Almangush & Tuula Salo

  3. Institute of Dentistry, University of Misurata, Misurata, Libya

    Alhadi Almangush

  4. Department of Pathology, University of Turku, Turku, Finland

    Ilmo Leivo

  5. Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland

    Maria Siponen, Elias Sundquist & Tuula Salo

  6. Department of Oral and Maxillofacial Diseases, Kuopio University Hospital, Kuopio, Finland

    Maria Siponen

  7. Institute of Dentistry, University of Eastern Finland, Kuopio, Finland

    Maria Siponen

  8. Medical Research Center, Oulu University Hospital, Oulu, Finland

    Elias Sundquist & Tuula Salo

  9. Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

    Rayan Mroueh & Antti A. Mäkitie

  10. Department of Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, and Cancer Center of Eastern Finland, Kuopio, Finland

    Ylermi Soini

  11. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    Caj Haglund

  12. Research Programs Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland

    Caj Haglund

  13. Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland

    Pentti Nieminen

  14. HUSLAB, Department of Pathology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland

    Tuula Salo

Authors
  1. Alhadi Almangush
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilmo Leivo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria Siponen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elias Sundquist
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rayan Mroueh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antti A. Mäkitie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ylermi Soini
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Caj Haglund
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pentti Nieminen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tuula Salo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alhadi Almangush.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-017-2212-1

Keywords

Search

Navigation