Abstract
Inflammation is associated with several tumor development and progression. However, these associations are not clear in well-differentiated thyroid carcinomas. We assessed whether NLR is a useful prognostic marker in patients with papillary thyroid carcinomas (PTC). The medical records of all patients who underwent thyroid surgery at a single institution between March 2005 and September 2012 were retrospectively evaluated; as a control group, patients who underwent routine health examinations in 2012 were also evaluated. Differences in mean NLR among patient groups were assessed, and clinical characteristics according to NLR quartile were evaluated in patients with PTC. The association between NLR and disease-free survival (DFS) in PTC patients was determined. NLR was significantly higher in the groups with than without thyroid nodules, but did not differ significantly in patients with benign and malignant thyroid nodules. Mean NLR was significantly higher in patients with solid or mixed thyroid than in patients with cystic nodules (1.75 ± 0.92 vs. 1.65 ± 0.74, p = 0.004). Patient follow-up ranged from 6 to 99 months. At 5-year follow-up, 11 patients had disease-specific events. We found that 5-year DFS rate was significantly worse in stages III and IV patients with NLR ≥1.5 than NLR <1.5 (94.1 vs. 99.3 %, p = 0.013). The univariate Cox hazard proportional hazard model for DFS revealed that higher NLR was independently correlated with poorer prognosis (hazard ratio 8.76; 95 % confidence interval 1.09–70.27, p = 0.041). Higher NLR may be a negative prognostic marker for DFS in patients with PTC, especially those with stages III and IV.
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References
L.M. Coussens, Z. Werb, Inflammation and cancer. Nature 420(6917), 860–867 (2002). doi:10.1038/nature01322
T.L. Whiteside, The tumor microenvironment and its role in promoting tumor growth. Oncogene 27(45), 5904–5912 (2008). doi:10.1038/onc.2008.271
H. Nozawa, C. Chiu, D. Hanahan, Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc. Natl Acad. Sci. USA 103(33), 12493–12498 (2006). doi:10.1073/pnas.0601807103
D.C. McMillan, The systemic inflammation-based Glasgow prognostic score: a decade of experience in patients with cancer. Cancer Treat. Rev. 39(5), 534–540 (2013). doi:10.1016/j.ctrv.2012.08.003
G.J. Guthrie, K.A. Charles, C.S. Roxburgh, P.G. Horgan, D.C. McMillan, S.J. Clarke, The systemic inflammation-based neutrophil-lymphocyte ratio: Experience in patients with cancer. Crit. Rev. Oncol. Hematol. (2013). doi:10.1016/j.critrevonc.2013.03.010
H. Yu, X. Huang, X. Liu, H. Jin, G. Zhang, Q. Zhang, J. Yu, Regulatory T cells and plasmacytoid dendritic cells contribute to the immune escape of papillary thyroid cancer coexisting with multinodular non-toxic goiter. Endocrine 44(1), 172–181 (2013). doi:10.1007/s12020-012-9853-2
M.H. Rho, D.W. Kim, H.P. Hong, Y.M. Park, M.J. Kwon, S.J. Jung, Y.W. Kim, T. Kang, Diagnostic value of antithyroid peroxidase antibody for incidental autoimmune thyroiditis based on histopathologic results. Endocrine 42(3), 647–653 (2012). doi:10.1007/s12020-012-9695-y
S.D. Larson, L.N. Jackson, T.S. Riall, T. Uchida, R.P. Thomas, S. Qiu, B.M. Evers, Increased incidence of well-differentiated thyroid cancer associated with Hashimoto thyroiditis and the role of the PI3k/Akt pathway. J. Am. Coll. Surg. 204(5), 764–773 (2007). doi:10.1016/j.jamcollsurg.2006.12.037. discussion 773–765
D.P. Bradly, V. Reddy, R.A. Prinz, P. Gattuso, Incidental papillary carcinoma in patients treated surgically for benign thyroid diseases. Surgery 146(6), 1099–1104 (2009). doi:10.1016/j.surg.2009.09.025
Y. Lun, X. Wu, Q. Xia, Y. Han, X. Zhang, Z. Liu, F. Wang, Z. Duan, S. Xin, J. Zhang, Hashimoto’s thyroiditis as a risk factor of papillary thyroid cancer may improve cancer prognosis. Otolaryngol. Head Neck Surg. 148(3), 396–402 (2013). doi:10.1177/0194599812472426
J.S. Jeong, H.K. Kim, C.R. Lee, S. Park, J.H. Park, S.W. Kang, J.J. Jeong, K.H. Nam, W.Y. Chung, C.S. Park, Coexistence of chronic lymphocytic thyroiditis with papillary thyroid carcinoma: clinical manifestation and prognostic outcome. J. Korean Med. Sci. 27(8), 883–889 (2012). doi:10.3346/jkms.2012.27.8.883
P. Del Rio, S. Cataldo, L. Sommaruga, L. Concione, M.F. Arcuri, M. Sianesi, The association between papillary carcinoma and chronic lymphocytic thyroiditis: does it modify the prognosis of cancer? Minerva Endocrinol. 33(1), 1–5 (2008)
E.Y. Kim, W.G. Kim, W.B. Kim, T.Y. Kim, J.M. Kim, J.S. Ryu, S.J. Hong, G. Gong, Y.K. Shong, Coexistence of chronic lymphocytic thyroiditis is associated with lower recurrence rates in patients with papillary thyroid carcinoma. Clin. Endocrinol. (Oxf) 71(4), 581–586 (2009). doi:10.1111/j.1365-2265.2009.03537.x
C.L. Liu, J.J. Lee, T.P. Liu, Y.C. Chang, Y.C. Hsu, S.P. Cheng, Blood neutrophil-to-lymphocyte ratio correlates with tumor size in patients with differentiated thyroid cancer. J. Surg. Oncol. 107(5), 493–497 (2013). doi:10.1002/jso.23270
B.D. Edge SB, C.C. Compton, A.G. Frits, F.L. Greene, A. Trotti, AJCC cancer staging manual, 7th edn. (Springer, New York, 2010)
H. Ubukata, G. Motohashi, T. Tabuchi, H. Nagata, S. Konishi, T. Tabuchi, Evaluations of interferon-gamma/interleukin-4 ratio and neutrophil/lymphocyte ratio as prognostic indicators in gastric cancer patients. J. Surg. Oncol. 102(7), 742–747 (2010). doi:10.1002/jso.21725
M. Aizawa, N. Gotohda, S. Takahashi, M. Konishi, T. Kinoshita, Predictive value of baseline neutrophil/lymphocyte ratio for T4 disease in wall-penetrating gastric cancer. World J. Surg. 35(12), 2717–2722 (2011). doi:10.1007/s00268-011-1269-2
M.R. Jung, Y.K. Park, O. Jeong, J.W. Seon, S.Y. Ryu, D.Y. Kim, Y.J. Kim, Elevated preoperative neutrophil to lymphocyte ratio predicts poor survival following resection in late stage gastric cancer. J. Surg. Oncol. 104(5), 504–510 (2011). doi:10.1002/jso.21986
R.Z. Sharaiha, K.J. Halazun, F. Mirza, J.L. Port, P.C. Lee, A.I. Neugut, N.K. Altorki, J.A. Abrams, Elevated preoperative neutrophil:lymphocyte ratio as a predictor of postoperative disease recurrence in esophageal cancer. Ann. Surg. Oncol. 18(12), 3362–3369 (2011). doi:10.1245/s10434-011-1754-8
M. Di Bari, F. Salvi, A.T. Roberts, D. Balzi, B. Lorenzetti, V. Morichi, L. Rossi, F. Lattanzio, N. Marchionni, Prognostic stratification of elderly patients in the emergency department: a comparison between the “Identification of Seniors at Risk” and the “Silver Code”. J. Gerontol. A 67(5), 544–550 (2012). doi:10.1093/gerona/glr209
Y. Mohri, K. Tanaka, M. Ohi, T. Yokoe, C. Miki, M. Kusunoki, Prognostic significance of host- and tumor-related factors in patients with gastric cancer. World J. Surg. 34(2), 285–290 (2010). doi:10.1007/s00268-009-0302-1
H. Shimada, N. Takiguchi, O. Kainuma, H. Soda, A. Ikeda, A. Cho, A. Miyazaki, H. Gunji, H. Yamamoto, M. Nagata, High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients with gastric cancer. Gastric Cancer 13(3), 170–176 (2010). doi:10.1007/s10120-010-0554-3
I. Bhatti, O. Peacock, G. Lloyd, M. Larvin, R.I. Hall, Preoperative hematologic markers as independent predictors of prognosis in resected pancreatic ductal adenocarcinoma: neutrophil-lymphocyte versus platelet-lymphocyte ratio. Am. J. Surg. 200(2), 197–203 (2010). doi:10.1016/j.amjsurg.2009.08.041
D.S. Wang, H.Y. Luo, M.Z. Qiu, Z.Q. Wang, D.S. Zhang, F.H. Wang, Y.H. Li, R.H. Xu, Comparison of the prognostic values of various inflammation based factors in patients with pancreatic cancer. Med. Oncol. 29(5), 3092–3100 (2012). doi:10.1007/s12032-012-0226-8
S.R. Walsh, E.J. Cook, F. Goulder, T.A. Justin, N.J. Keeling, Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J. Surg. Oncol. 91(3), 181–184 (2005). doi:10.1002/jso.20329
H.C. Kwon, S.H. Kim, S.Y. Oh, S. Lee, J.H. Lee, H.J. Choi, K.J. Park, M.S. Roh, S.G. Kim, H.J. Kim, J.H. Lee, Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer. Biomarkers 17(3), 216–222 (2012). doi:10.3109/1354750X.2012.656705
T. Motomura, K. Shirabe, Y. Mano, J. Muto, T. Toshima, Y. Umemoto, T. Fukuhara, H. Uchiyama, T. Ikegami, T. Yoshizumi, Y. Soejima, Y. Maehara, Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J. Hepatol. 58(1), 58–64 (2013). doi:10.1016/j.jhep.2012.08.017
M. Tomita, T. Shimizu, T. Ayabe, A. Yonei, T. Onitsuka, Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer. Anticancer Res. 31(9), 2995–2998 (2011)
T. Gondo, J. Nakashima, Y. Ohno, O. Choichiro, Y. Horiguchi, K. Namiki, K. Yoshioka, M. Ohori, T. Hatano, M. Tachibana, Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology 79(5), 1085–1091 (2012). doi:10.1016/j.urology.2011.11.070
S. Teramukai, T. Kitano, Y. Kishida, M. Kawahara, K. Kubota, K. Komuta, K. Minato, T. Mio, Y. Fujita, T. Yonei, K. Nakano, M. Tsuboi, K. Shibata, K. Furuse, M. Fukushima, Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03. Eur. J. Cancer 45(11), 1950–1958 (2009). doi:10.1016/j.ejca.2009.01.023
O.K. Idowu, Q. Ding, A.F. Taktak, C.R. Chandrasekar, Q. Yin, Clinical implication of pretreatment neutrophil to lymphocyte ratio in soft tissue sarcoma. Biomarkers 17(6), 539–544 (2012). doi:10.3109/1354750X.2012.699554
H. Cho, H.W. Hur, S.W. Kim, S.H. Kim, J.H. Kim, Y.T. Kim, K. Lee, Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol. Immunother. 58(1), 15–23 (2009). doi:10.1007/s00262-008-0516-3
J.-D. Lin, C. Hsueh, T.-C. Chao, Early recurrence of papillary and follicular thyroid carcinoma predicts a worse outcome. Thyroid 19(10), 1053–1059 (2009). doi:10.1089/thy.2009.0133
C. Seretis, S. Gourgiotis, G. Gemenetzis, F. Seretis, E. Lagoudianakis, G. Dimitrakopoulos, The significance of neutrophil/lymphocyte ratio as a possible marker of underlying papillary microcarcinomas in thyroidal goiters: a pilot study. Am. J. Surg. 205(6), 691–696 (2013). doi:10.1016/j.amjsurg.2012.08.006
K. Pietras, A. Ostman, Hallmarks of cancer: interactions with the tumor stroma. Exp. Cell Res. 316(8), 1324–1331 (2010). doi:10.1016/j.yexcr.2010.02.045
C.S. Roxburgh, D.C. McMillan, Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 6(1), 149–163 (2010). doi:10.2217/fon.09.136
H.T. Petrie, L.W. Klassen, H.D. Kay, Inhibition of human cytotoxic T lymphocyte activity in vitro by autologous peripheral blood granulocytes. J. Immunol. 134(1), 230–234 (1985)
H.D. Kay, D.L. Smith, Regulation of human lymphocyte-mediated natural killer (NK) cell activity. I. Inhibition in vitro by peripheral blood granulocytes. J. Immunol. 130(1), 475–483 (1983)
H.Y. Shau, A. Kim, Suppression of lymphokine-activated killer induction by neutrophils. J. Immunol. 141(12), 4395–4402 (1988)
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Kim, JY., Park, T., Jeong, SH. et al. Prognostic importance of baseline neutrophil to lymphocyte ratio in patients with advanced papillary thyroid carcinomas. Endocrine 46, 526–531 (2014). https://doi.org/10.1007/s12020-013-0089-6
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DOI: https://doi.org/10.1007/s12020-013-0089-6