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Clinical Oral Investigations

, Volume 22, Issue 3, pp 1311–1318 | Cite as

Progression level of extracapsular spread and tumor budding for cervical lymph node metastasis of OSCC

  • Shin-ichi Yamada
  • Mitsunobu Otsuru
  • Souichi Yanamoto
  • Takumi Hasegawa
  • Hitoshi Aizawa
  • Takahiro Kamata
  • Nobuhiro Yamakawa
  • Tomoyuki Kohgo
  • Akira Ito
  • Yuri Noda
  • Chihoko Hirai
  • Tetsuya Kitamura
  • Masaya Okura
  • Tadaaki Kirita
  • Michihiro Ueda
  • Tetsuro Yamashita
  • Yoshihide Ota
  • Takahide Komori
  • Masahiro Umeda
  • Hiroshi Kurita
Original Article
  • 210 Downloads

Abstract

Objectives

The progression level of extracapsular spread (ECS) for cervical lymph node metastasis of oral squamous cell carcinoma (OSCC) was previously divided into three types, and their relationships with the prognosis of patients were re-examined.

Patients and methods

The Kaplan-Meier method was used to examine overall survival (OS) and relapse-free survival (RFS) curves. Prognosis factor for recurrence was analyzed with univariate and multivariate analysis.

Results

ECS was detected in 216 cases of OSCC and analyzed. The 5-year overall survival and RFS rates of patients with type C, which was microscopically defined as tumor invasion to perinodal fat or muscle tissue, were significantly poor at 40.6 and 37.8%, respectively. The results of a univariate analysis suggested that the prognosis of ECS in OSCC patients is associated with its progression level, particularly type C. The 5-year RFS rate of type C with tumor budding was significantly poor at 31.5%. Type C with tumor budding correlated with local and regional recurrence as well as distant metastasis. In a multivariate analysis, tumor budding was identified as an independent prognostic factor.

Conclusions

These results suggest that the progression level of ECS and tumor budding are useful prognostic factors in OSCC patients.

Clinical relevance

This study indicated that the progression level and tumor budding of ECS for cervical lymph node metastasis were useful prognostic factors in OSCC patients.

Keywords

Cervical lymph node metastasis Extracapsular spread Oral squamous cell carcinoma Prognostic factor Tumor budding 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

References

  1. 1.
    Johnson NW, Jayasekara D, Amarasinghe AA (2011) Squamous cell carcinoma and precursor lesions of the oral cavity: epidemiology and aetiology. Periodontol 57(1):19–37CrossRefGoogle Scholar
  2. 2.
    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(2):167–178CrossRefPubMedGoogle Scholar
  3. 3.
    Kademani D, Bell RB, Bagheri S, Holmgren E, Dierks E, Potter B, Homer L (2005) Prognostic factors in intraoral squamous cell carcinoma: the influence of histologic grade. J Oral Maxillofac Surg 63(11):1599–1605CrossRefPubMedGoogle Scholar
  4. 4.
    Arduino PG, Carrozzo M, Chiecchio A, Broccoletti R, Tirone F, Borra E, Bertolusso G, Gandolfo S (2008) Clinical and histopathologic independent prognostic factors in oral squamous cell carcinoma: a retrospective study of 334 cases. J Oral Maxillofac Surg 66(8):1570–1579CrossRefPubMedGoogle Scholar
  5. 5.
    Myers JN, Greenberg JS, Mo V, Roberts D (2001) Extracapsular spread. A significant predictor of treatment failure in patients with squamous cell carcinoma of the tongue. Cancer 92(12):3030–3036CrossRefPubMedGoogle Scholar
  6. 6.
    Greenberg JS, Fowler R, Gomez J, Mo V, Roberts D, El Naggar AK, Myers JN (2003) Extent of extracapsular spread: a critical prognosticator in oral tongue cancer. Cancer 97(6):1464–1470CrossRefPubMedGoogle Scholar
  7. 7.
    Woolgar JA, Rogers SN, Lowe D, Brown JS, Vaughan ED (2003) Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread. Oral Oncol 39(2):130–137CrossRefPubMedGoogle Scholar
  8. 8.
    Shaw RJ, Lowe D, Woolgar JA, Brown JS, Vaughan ED, Evans C, Lewis-Jones H, Hanlon R, Hall GL, Rogers SN (2010) Extracapsular spread in oral squamous cell carcinoma. Head Neck 32(6):714–722PubMedGoogle Scholar
  9. 9.
    Shibuya Y, Hasegawa T, Akashi M, Shigeta T, Minamikawa T, Komori T (2013) Oral squamous cell carcinoma with multiple neck metastases—cases with more than ten pathologically positive lymph nodes in the unilateral side. J Oral Maxillofac Surg 71(4):793–797CrossRefPubMedGoogle Scholar
  10. 10.
    Prabhu RS, Hanasoge S, Magliocca KR, Moeller BJ, Milas ZL, Hall WA, El-Deiry M, Wadsworth JT, Higgins KA, Beitler JJ (2014) Extent of pathologic extracapsular extension and outcomes in patients with nonoropharyngeal head and neck cancer treated with initial surgical resection. Cancer 120(10):1499–1506CrossRefPubMedGoogle Scholar
  11. 11.
    Wreesmann VB, Katabi N, Palmer FL, Montero PH, Migliacci JC, Gönen M, Carlson D, Ganly I, Shah JP, Ghossein R, Patel SG (2016) Influence of extracapsular nodal spread extent on prognosis of oral squamous cell carcinoma. Head Neck 38:E1192–E1199.  https://doi.org/10.1002/hed.24190 CrossRefPubMedGoogle Scholar
  12. 12.
    Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M; European Organization for Research and Treatment of Cancer Trial 22931 (2004) Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350(19):1945–1952Google Scholar
  13. 13.
    Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup (2004) Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350(19):1937–1944Google Scholar
  14. 14.
    Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin EM, Jacobs JR, Jassem J, Ang KK, Lefèbvre JL (2005) Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (#9501). Head Neck 27(10):843–850CrossRefPubMedGoogle Scholar
  15. 15.
    Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Lustig R, Ensley JF, Thorstad W, Schultz CJ, Yom SS, Ang KK (2012) Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 84(5):1198–1205CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Yamada S, Yanamoto S, Otani S, Hasegawa T, Miyakoshi M, Minamikawa T, Ohga N, Kamata T, Komori T, Kitagawa Y, Kurita H, Umeda M (2016) Evaluation of the level of progression of extracapsular spread for cervical lymph node metastasis in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 45(2):141–146CrossRefPubMedGoogle Scholar
  17. 17.
    Ueno H, Mochizuki H, Hashiguchi Y, Shimazaki H, Aida S, Hase K, Matsukuma S, Kanai T, Kurihara H, Ozawa K, Yoshimura K, Bekku S (2004) Risk factors for an adverse outcome in early invasive colorectal carcinoma. Gastroenterology 127(2):385–394CrossRefPubMedGoogle Scholar
  18. 18.
    Prall F (2007) Tumour budding in colorectal carcinoma. Histopathology 50(1):151–162CrossRefPubMedGoogle Scholar
  19. 19.
    Landau MS, Hastings SM, Foxwell TJ, Luketich JD, Nason KS, Davison JM (2014) Tumor budding is associated with an increased risk of lymph node metastasis and poor prognosis in superficial esophageal adenocarcinoma. Mod Pathol 27(1):1578–1589CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    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(4):266–272CrossRefPubMedGoogle Scholar
  21. 21.
    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(7):545–551CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Almangush A, Bello IO, Keski-Säntti H, Mäkinen LK, Kauppila JH, Pukkila M, Hagström J, Laranne J, Tommola S, Nieminen O, Soini Y, Kosma VM, Koivunen P, Grénman 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(6):811–818CrossRefPubMedGoogle Scholar
  23. 23.
    Marangon Junior H, Rocha VN, Leite CF, de Aguiar MC, Souza PE, Horta MC (2014) Laminin-5 gamma 2 chain expression is associated with intensity of tumor budding and density of stromal myofibroblasts in oral squamous cell carcinoma. J Oral Pathol Med 43(3):199–204CrossRefPubMedGoogle Scholar
  24. 24.
    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(Suppl1):E1582–E1590.  https://doi.org/10.1002/hed.24282 CrossRefPubMedGoogle Scholar
  25. 25.
    Kang CJ, Lin CY, Wang HM, Fan KH, Ng SH, Lee LY, Chen IH, Huang SF, Liao CT, Yen TC (2011) The number of pathologically positive lymph nodes and pathological tumor depth predicts prognosis in patients with poorly differentiated squamous cell carcinoma of the oral cavity. Int J Radiat Oncol Biol Phys 81(4):223–230CrossRefGoogle Scholar
  26. 26.
    Liao CT, Wang HM, Chang JT, Ng SH, Hsueh C, Lee LY, Lin CH, Chen IH, Huang SF, Yen TC (2007) Analysis of risk factors for distant metastases in squamous cell carcinoma of the oral cavity. Cancer 110(7):1501–1508CrossRefPubMedGoogle Scholar
  27. 27.
    Fan S, Tang QL, Lin YJ, Chen WL, Li JS, Huang ZQ, Yang ZH, Wang YY, Zhang DM, Wang HJ, Dias-Ribeiro E, Cai Q, Wang L (2011) A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma. Int J Oral Sci 3(4):180–191CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Liao CT, Hsueh C, Lee LY, Lin CY, Fan KH, Wang HM, Huang SF, Chen IH, Kang CJ, Ng SH, Tsao CK, Huang YC, Yen TC (2012) Neck dissection field and lymph node density predict prognosis in patients with oral cavity cancer and pathological node metastases treated with adjuvant therapy. Oral Oncol 48(4):329–336CrossRefPubMedGoogle Scholar
  29. 29.
    Gil Z, Carlson DL, Boyle JO, Kraus DH, Shah JP, Shaha AR, Singh B, Wong RJ, Patel SG (2009) Lymph node density is a significant predictor of outcome in patients with oral cancer. Cancer 115(24):5700–5710CrossRefPubMedGoogle Scholar
  30. 30.
    Kiyota N, Tahara M, Okano S, Kawashima M, Matsuura K, Onozawa Y, Nibu K, Hayashi R, Yoshimura K, Ohtsu A (2012) Phase II feasibility trial of adjuvant chemoradiotherapy with 3-weekly cisplatin for Japanese patients with post-operative high-risk squamous cell carcinoma of the head and neck. Jpn J Clin Oncol 42(10):927–933CrossRefPubMedGoogle Scholar
  31. 31.
    Brasilino de Carvalho M (1998) Quantitative analysis of the extent of extracapsular invasion and its prognostic significance: a prospective study of 170 cases of carcinoma of the larynx and hypopharynx. Head Neck 20(1):16–21CrossRefPubMedGoogle Scholar
  32. 32.
    Alvi A, Johnson JT (1996) Extracapsular spread in the clinically negative neck (N0): implications and outcome. Otolaryngol Head Neck Surg 114(1):65–70CrossRefPubMedGoogle Scholar
  33. 33.
    Jose J, Coatesworth AP, Johnston C, MacLennan K (2003) Cervical node metastases in squamous cell carcinoma of the upper aerodigestive tract: the significance of extracapsular spread and soft tissue deposits. Head Neck 25(6):451–456CrossRefPubMedGoogle Scholar
  34. 34.
    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(11):6111–6120PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Shin-ichi Yamada
    • 1
  • Mitsunobu Otsuru
    • 2
  • Souichi Yanamoto
    • 3
  • Takumi Hasegawa
    • 4
  • Hitoshi Aizawa
    • 1
  • Takahiro Kamata
    • 1
  • Nobuhiro Yamakawa
    • 5
  • Tomoyuki Kohgo
    • 6
  • Akira Ito
    • 7
  • Yuri Noda
    • 8
  • Chihoko Hirai
    • 9
  • Tetsuya Kitamura
    • 10
  • Masaya Okura
    • 7
  • Tadaaki Kirita
    • 5
  • Michihiro Ueda
    • 6
  • Tetsuro Yamashita
    • 6
  • Yoshihide Ota
    • 2
  • Takahide Komori
    • 4
  • Masahiro Umeda
    • 3
  • Hiroshi Kurita
    • 1
  1. 1.Department of Dentistry and Oral SurgeryShinshu University School of MedicineMatsumotoJapan
  2. 2.Department of Oral and Maxillofacial Surgery, Division of SurgeryTokai University School of MedicineIseharaJapan
  3. 3.Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental SciencesNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  4. 4.Department of Oral and Maxillofacial SurgeryKobe University Graduate School of MedicineKobeJapan
  5. 5.Department of Oral and Maxillofacial Surgery, School of MedicineNara Medical UniversityKashiharaJapan
  6. 6.Department of Oral and Maxillofacial SurgeryKeiyukai Sapporo HospitalSapporoJapan
  7. 7.The 1st Department of Oral and Maxillofacial Surgery, Graduate School of DentistryOsaka UniversitySuitaJapan
  8. 8.Department of Oral PathologyOsaka University Graduate School of DentistrySuitaJapan
  9. 9.Department of Diagnostic PathologyKobe University HospitalKobeJapan
  10. 10.Department of Oral Pathology and BiologyHokkaido University Graduate School of Dental MedicineSapporoJapan

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