Skip to main content

Advertisement

SpringerLink
Log in

Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis

  • Head & Neck
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Purpose

Most tumors have obvious biologically active fibroblasts known variously as myofibroblasts or cancer-associated fibroblasts (CAFs) in the stroma. CAFs have been known as an important factor of cancer invasion and metastasis. This study aimed to investigate the presence of CAFs in patients with papillary thyroid carcinoma (PTC) and evaluate the correlation between CAFs and cervical lymph node (LN) metastasis in PTC through immunohistochemistry.

Methods

The medical records of 128 patients who were diagnosed with PTC from January 1, 2010 to December 31, 2010 were reviewed, and 78 patients who underwent total thyroidectomy with or without neck dissection, were included in this study. A retrospective pathological evaluation was performed to verify the presence of CAFs. CD34 and α-smooth muscle actin (SMA) were used as markers of CAFs.

Results

Among 78 patients with PTC, 65 had desmoplastic stromal reaction around the PTC. Through immunohistochemical study of anti-CD34 and α-SMA antibodies, CAFs were found in 42 (64.6%) cases with desmoplastic stroma around the PTC. Univariate analysis showed that tumor size and CAFs were the risk factors of LN metastasis in patients with PTC, while multivariate analysis revealed that CAFs were the only independent risk factor of LN metastasis in patients with PTC.

Conclusion

This study revealed the presence of CAFs in PTC. Furthermore, CAFs were found to be a risk factor of LN metastasis in PTC. Therefore, CAFs may be used as a predictive marker for LN metastasis in patients with PTC.

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
Fig. 2

Similar content being viewed by others

References

  1. Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 295:2164–2167. https://doi.org/10.1001/jama.295.18.2164

    Article  PubMed  CAS  Google Scholar 

  2. Davies L, Welch HG (2010) Thyroid cancer survival in the United States: observational data from 1973 to 2005. Arch Otolaryngol Head Neck Surg 136:440–444. https://doi.org/10.1001/archoto.2010.55

    Article  PubMed  Google Scholar 

  3. Lundgren CI, Hall P, Dickman PW, Zedenius J (2006) Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case-control study. Cancer 106:524–531. https://doi.org/10.1002/cncr.21653

    Article  PubMed  Google Scholar 

  4. Noguchi S, Murakami N, Yamashita H, Toda M, Kawamoto H (1998) Papillary thyroid carcinoma: modified radical neck dissection improves prognosis. Arch Surg 133:276–280

    Article  PubMed  CAS  Google Scholar 

  5. Podnos YD, Smith D, Wagman LD, Ellenhorn JD (2005) The implication of lymph node metastasis on survival in patients with well-differentiated thyroid cancer. Am Surg 71:731–734

    PubMed  Google Scholar 

  6. Tubiana M, Schlumberger M, Rougier P, Laplanche A, Benhamou E, Gardet P, Caillou B, Travagli JP, Parmentier C (1985) Long-term results and prognostic factors in patients with differentiated thyroid carcinoma. Cancer 55:794–804

    Article  PubMed  CAS  Google Scholar 

  7. American Thyroid Association Guidelines Taskforce on Thyroid N, Differentiated Thyroid C, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM (2009) Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 19:1167–1214. https://doi.org/10.1089/thy.2009.0110

    Article  Google Scholar 

  8. Hasney CP, Amedee RG (2010) What is the appropriate extent of lateral neck dissection in the treatment of metastatic well-differentiated thyroid carcinoma? Laryngoscope 120:1716–1717. https://doi.org/10.1002/lary.20994

    Article  PubMed  Google Scholar 

  9. Conzo G, Mauriello C, Docimo G, Gambardella C, Thomas G, Cavallo F, Tartaglia E, Napolitano S, Varriale R, Rossetti G, Fei L, Santini L (2014) Clinicopathological pattern of lymph node recurrence of papillary thyroid cancer. Implications for surgery. Int J Surg 12:S194–S197. https://doi.org/10.1016/j.ijsu.2014.05.010

    Article  PubMed  Google Scholar 

  10. Liotta LA, Kohn EC (2001) The microenvironment of the tumour-host interface. Nature 411:375–379. https://doi.org/10.1038/35077241

    Article  PubMed  CAS  Google Scholar 

  11. Franco OE, Shaw AK, Strand DW, Hayward SW (2010) Cancer associated fibroblasts in cancer pathogenesis. Semin Cell Dev Biol 21:33–39. https://doi.org/10.1016/j.semcdb.2009.10.010

    Article  PubMed  CAS  Google Scholar 

  12. Koperek O, Asari R, Niederle B, Kaserer K (2011) Desmoplastic stromal reaction in papillary thyroid microcarcinoma. Histopathology 58:919–924. https://doi.org/10.1111/j.1365-2559.2011.03791.x

    Article  PubMed  Google Scholar 

  13. Madar S, Goldstein I, Rotter V (2013) “Cancer associated fibroblasts”—more than meets the eye. Trends Mol Med 19:447–453. https://doi.org/10.1016/j.molmed.2013.05.004

    Article  PubMed  CAS  Google Scholar 

  14. Daoud SA, Esmail RS, Hareedy AA, Khalil A (2015) Stromal modulation and its role in the diagnosis of papillary patterned thyroid lesions. APJCP 16:3307–3312

    PubMed  Google Scholar 

  15. Scheuba C, Kaserer K, Kaczirek K, Asari R, Niederle B (2006) Desmoplastic stromal reaction in medullary thyroid cancer-an intraoperative “marker” for lymph node metastases. World J Surg 30:853–859. https://doi.org/10.1007/s00268-005-0391-4

    Article  PubMed  Google Scholar 

  16. Sun WY, Jung WH, Koo JS (2015) Expression of cancer-associated fibroblast-related proteins in thyroid papillary carcinoma. Tumour Biol. https://doi.org/10.1007/s13277-015-4684-4

    Article  PubMed  PubMed Central  Google Scholar 

  17. Tuxhorn JA, McAlhany SJ, Dang TD, Ayala GE, Rowley DR (2002) Stromal cells promote angiogenesis and growth of human prostate tumors in a differential reactive stroma (DRS) xenograft model. Cancer Res 62:3298–3307

    PubMed  CAS  Google Scholar 

  18. Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315:1650–1659. https://doi.org/10.1056/NEJM198612253152606

    Article  PubMed  CAS  Google Scholar 

  19. Li J, Wei F (2015) Retrospective analysis of TGF-beta 1 expression in patients with thyroidectomy. Cancer Biomark 15:693–698. https://doi.org/10.3233/CBM-150510

    Article  PubMed  CAS  Google Scholar 

  20. Barth PJ, Schenck zu Schweinsberg T, Ramaswamy A, Moll R (2004) CD34+ fibrocytes, alpha-smooth muscle antigen-positive myofibroblasts, and CD117 expression in the stroma of invasive squamous cell carcinomas of the oral cavity, pharynx, and larynx. Virchows Archiv 444:231–234. https://doi.org/10.1007/s00428-003-0965-1

    Article  PubMed  CAS  Google Scholar 

  21. Nakayama H, Enzan H, Miyazaki E, Kuroda N, Naruse K, Hiroi M (2000) Differential expression of CD34 in normal colorectal tissue, peritumoral inflammatory tissue, and tumour stroma. J Clin Pathol 53:626–629

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Shiga K, Hara M, Nagasaki T, Sato T, Takahashi H, Takeyama H (2015) Cancer-associated fibroblasts: their characteristics and their roles in tumor growth. Cancers (Basel) 7:2443–2458. https://doi.org/10.3390/cancers7040902

    Article  Google Scholar 

Download references

Funding

This study was funded by Korea University Grant.

Author information

Authors and Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, Korea University College of Medicine, Guro-dong 80, Guro-gu, Seoul, 152-703, South Korea

    Jae-Gu Cho, Hyung Kwon Byeon, Kyung Ho Oh, Seung-Kuk Baek, Soon-Young Kwon, Kwang-Yoon Jung & Jeong-Soo Woo

Authors
  1. Jae-Gu Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyung Kwon Byeon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kyung Ho Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seung-Kuk Baek
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Soon-Young Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kwang-Yoon Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jeong-Soo Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeong-Soo Woo.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study is a retrospective data review with a pathologic slide.

Informed consent

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cho, JG., Byeon, H.K., Oh, K.H. et al. Clinicopathological significance of cancer-associated fibroblasts in papillary thyroid carcinoma: a predictive marker of cervical lymph node metastasis. Eur Arch Otorhinolaryngol 275, 2355–2361 (2018). https://doi.org/10.1007/s00405-018-5061-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-018-5061-x

Keywords

Search

Navigation