DOI QR코드

DOI QR Code

Is the Tumor Infiltrating Natural Killer Cell (NK-TILs) Count in Infiltrating Ductal Carcinoma of Breast Prognostically Significant?

  • Published : 2014.04.30

Abstract

Purpose: The aim of this study was to investigate the prognostic significance of the CD56+NK-TIL count in infiltrating ductal carcinoma (IDC) of breast. Material and Methods: Immunohistochemistry (IHC) was performed using antibodies specific for CD56 on formalin-fixed and paraffin-embedded tissue sections of 175 infiltrating ductal carcinomas (IDC) of breast. Distribution of intratumoral and stromal CD56+NK-TILs was assessed semi-quantitatively. Results: A low intratumoral CD56+count showed significant and inverse associations with tumor grade, stage, and lymph node status, whereas it had significant and direct association with response to treatment indicating good prognosis. These patients had better survival (${\chi}^2$=4.80, p<0.05) and 0.52 fold lower death rate (HR=0.52, 95% CI=0.28-0.93) as compared to patients with high CD56+ intratumoral count. The association of survival was insignificant with low CD56 stromal count as compared to high CD56 stromal count (${\chi}^2$=1.60, p>0.05). Conclusion: To conclude, although NK-TIL count appeared as a significant predictor of prognosis, it alone may not be sufficient for predicting the outcome considering the fact that there exists a crosstalk between NK-TILs and the other immune infiltrating TILs.

Keywords

References

  1. Abbott JJ, Amirkhan RH, Hoang MP, (2004). Malignant melanoma with a rhabdoid phenotype histologic, immunohistochemical, and ultrastructural study of a case and review of the literature. Arch Pathol Lab Med, 128, 686-6.
  2. Cho EY, Choi Y, Chae SW, et al (2006). Immunohistochemical study of the expression of adhesion molecules in ovarian serous neoplasms. Pathol Int, 56, 62-70. https://doi.org/10.1111/j.1440-1827.2006.01925.x
  3. Choi YL, Xuan YH, Shin YK, et al (2004). An immunohistochemical study of the expression of adhesion molecules in gallbladder lesions. J Histochem Cytochem, 52, 591-01. https://doi.org/10.1177/002215540405200504
  4. Coca S, Perez-Piqueras J, Martinez D, et al (1997). The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer, 79, 2320-8. https://doi.org/10.1002/(SICI)1097-0142(19970615)79:12<2320::AID-CNCR5>3.0.CO;2-P
  5. Daniel L, Bouvier C, Chetaille B, et al (2003). Neural cell adhesion molecule expression in renal cell carcinomas relation to metastatic behavior. Hum Pathol, 34, 528-32. https://doi.org/10.1016/S0046-8177(03)00178-3
  6. Denkert C, Loibl S, Noske A, et al (2010). Tumor associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol, 28, 105-13. https://doi.org/10.1200/JCO.2009.23.7370
  7. D'Souza ND, Murthy NS, Aras RY (2013a). Projection of cancer incident cases for India -till 2026. Asian Pac J Cancer Prev, 14, 4379-86. https://doi.org/10.7314/APJCP.2013.14.7.4379
  8. D'Souza ND, Murthy NS, Aras RY (2013b). Projection of burden of cancer mortality for India, 2011-2026. Asian Pac J Cancer Prev, 14, 4387-92. https://doi.org/10.7314/APJCP.2013.14.7.4387
  9. Deschoolmeester V, Baay M, Van Marck E, et al (2010). Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients. BMC Immunol, 11, 1-12. https://doi.org/10.1186/1471-2172-11-1
  10. Evans AJ, Humphrey PA, Belani J, et al (2006). Large cell neuroendocrine carcinoma of prostatea clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer. Am J Surg Pathol, 30, 684-93. https://doi.org/10.1097/00000478-200606000-00003
  11. Farinola MA, Weir EG, Ali SZ (2003). CD56 expression of neuroendocrine neoplasms on immunophenotyping by flow cytometry a novel diagnostic approach to fine-needle aspiration biopsy. Cancer, 99, 240-6. https://doi.org/10.1002/cncr.11458
  12. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008 : Globocan 2008, Int J Cancer, 127, 2893-17. https://doi.org/10.1002/ijc.25516
  13. Finak G, Bertos N, Pepin F, et al (2008). Stromal gene expression predicts clinical outcome in breast cancer. Nat Med, 14, 518-27. https://doi.org/10.1038/nm1764
  14. Fregni G, Perier A, Avril MF, et al (2012). NK cells sense tumors, course of disease and treatments Consequences for NK-based therapies. Oncoimmunology, 1, 38-47. https://doi.org/10.4161/onci.1.1.18312
  15. Gannon PO, Poisson AO, Delvoye N, et al (2009). Characterization of the intra-prostatic immune cell infiltration in androgendeprived prostate cancer patients. J Immunol Methods, 348, 9-17. https://doi.org/10.1016/j.jim.2009.06.004
  16. Gardner LJ, Polski JM, Fallon R, et al (1998). Identification of CD56 and CD57 by flow cytometry in Ewing’s sarcoma or primitive neuroectodermal tumor. Virchows Arch, 433, 35-40. https://doi.org/10.1007/s004280050213
  17. Greene FL, Page D, Morrow M, et al (2002). AJCC Cancer Staging Manual. 6th ed. New York: Springer, 157-64.
  18. Jochems C, Schlom J, (2011). Tumor-infiltrating immune cells and prognosis: the potential link between conventional cancer therapy and immunity. Experimental Biology and Medicine, 236, 567-79. https://doi.org/10.1258/ebm.2011.011007
  19. Johnson JP (1999). Cell adhesion molecules in the development and progression of malignant melanoma. Cancer Metastasis Rev, 18, 345-57. https://doi.org/10.1023/A:1006304806799
  20. Key T J, Verkasalo P K, Banks E (2001). Epidemiology of breast cancer. Lancet Oncol, 2, 133-40. https://doi.org/10.1016/S1470-2045(00)00254-0
  21. Kim R, Emi M, Kazuaki Tanabe K (2007). Cancer immunoediting from immune surveillance to immune escape. Immunology, 121, 1-14. https://doi.org/10.1111/j.1365-2567.2007.02587.x
  22. Levy EM, Roberti MP, Mordoh J, et al (2011). Natural killer cells in human cancer: from biological functions to clinical applications. J Biomed Biotechnol, 2011, 1-11.
  23. Lipinski M, Hirsch MR, Deagostini-Bazin H, et al (1987). Characterization of neural cell adhesion molecules (NCAM) expressed by Ewing and neuroblastoma cell lines. Int J Cancer, 40, 81-86. https://doi.org/10.1002/ijc.2910400115
  24. McKenzie JL, Allen AK, Fabre JW, et al (1981). Human thy-1 unusual localization and possible functional significance in lymphoid tissues. J Immunol, 126, 843-850.
  25. Mamessier E, Bertucci F, Sabatier R, (2012). “Stealth” tumors:Breast cancer cells shun NK-cells anti-tumor immunity. Oncoimmunology, 1, 366-68. https://doi.org/10.4161/onci.18528
  26. Mamessier E, Sylvain A, Thibult ML, et al (2011). Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J Clin Invest, 121, 3609-22. https://doi.org/10.1172/JCI45816
  27. Poli A, Michel T, Theresine M, et al (2009). CD56bright natural killer (NK) cells: an important NK cell subset. Immunology, 126, 458-65. https://doi.org/10.1111/j.1365-2567.2008.03027.x
  28. Pujol JL, Simony J, Demoly P, et al (1993). Neural cell adhesion molecule and prognosis of surgically resected lung cancer. Am Rev Respir Dis, 148, 1071-75. https://doi.org/10.1164/ajrccm/148.4_Pt_1.1071
  29. Stojanovic A, Cerwenka A (2011). Natural killer cells and Solid tumors. J Innate Immun, 3, 355-64. https://doi.org/10.1159/000325465
  30. Tavassoli FA, Devilee P (2003). World health organization classification of tumours. in pathology and genetics tumours of the breast and female genital organs. Lyon IARC Press, 2003.
  31. Wittekind Ch, Henson DE, Hutter RVP, et al (2001). International union against cancer (UICC): TNM supplement. a commentary on uniform use 2nd ed, New York: Wiley.
  32. Zoltowska A, Stepinski J, Lewko B, et al (2001). Neural cell adhesion molecule in breast, colon and lung carcinomas. Arch Immunol Ther Exp, 49, 171-4.

Cited by

  1. Prognostic significance of CD169-positive lymph node sinus macrophages in patients with endometrial carcinoma vol.107, pp.6, 2016, https://doi.org/10.1111/cas.12929
  2. The immune system and cancer evasion strategies: therapeutic concepts vol.279, pp.6, 2016, https://doi.org/10.1111/joim.12470
  3. Tumor-infiltrating lymphocytes and breast cancer: Beyond the prognostic and predictive utility vol.39, pp.4, 2017, https://doi.org/10.1177/1010428317695023
  4. Prognostic Value of Tumor-Infiltrating Lymphocyte Density Assessed Using a Standardized Method Based on Molecular Subtypes and Adjuvant Chemotherapy in Invasive Breast Cancer vol.25, pp.4, 2018, https://doi.org/10.1245/s10434-017-6332-2
  5. Downregulation of MCT4 for lactate exchange promotes the cytotoxicity of NK cells in breast carcinoma vol.7, pp.9, 2018, https://doi.org/10.1002/cam4.1713