Remember Me
Or use your Academic/Social account:


Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Tewari, Nilanjana; Zaitoun, Abed M.; Arora, Arvind; Madhusudan, Srinivasan; Ilyas, Mohammad; Lobo, Dileep N. (2013)
Publisher: BioMed Central
Journal: BMC Cancer
Languages: English
Types: Article
Subjects: Research Article, CD3, Genetics, CD8, Tumour-associated lymphocytes, Immunohistochemistry, Prognosis, Cancer Research, Oncology, Pancreatic ductal adenocarcinoma
Background\ud Tumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma.\ud \ud Methods\ud After histological re-evaluation of the tumours of 81 patients who underwent surgical resection for exclusively pancreatic ductal adenocarcinoma, tissue micro-arrays (TMA) were constructed and immunohistochemistry was performed for CD3, CD8 and CD20. The number of lymphocytes within specific tumour compartments (i.e. stromal and intratumoural) was quantified. X-tile software (Yale School of Medicine, CT, USA) was used to stratify patients into 'high’ and 'low’ for each of the lymphocytes stained and their association with survival. Receiver operating curves (ROC) were constructed to evaluate the association between the TALs, alone and in combination, with clinicopathological features.\ud \ud Results\ud CD3 and CD8 positive lymphocytes were associated with grade of tumour differentiation. The presence of intratumoural CD3 positive cells was associated with improved survival (p = 0.028), and intratumoural and stromal CD3 in combination also correlated with improved survival (p = 0.043). When CD20 positive lymphocyte levels were high, survival improved (p = 0.029) and similar results were seen for CD20 in combination with intratumoural CD3 (p = 0.001) and stromal CD8 (p = 0.013).\ud \ud Conclusions\ud This study has shown a correlation between the presence of TALs and survival in pancreatic ductal adenocarcinoma.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Maitra A, Hruban RH: Pancreatic cancer. Annu Rev Pathol 2008, 3:157-188.
    • 2. Saif MW: Pancreatic neoplasm in 2011: an update. JOP 2011, 12:316-321.
    • 3. Heinemann V, Haas M, Boeck S: Systemic treatment of advanced pancreatic cancer. Canc Treat Rev 2012, 38:843-853.
    • 4. Ying JE, Zhu LM, Liu BX: Developments in metastatic pancreatic cancer: is gemcitabine still the standard? World J Gastroenterol 2012, 18:736-745.
    • 5. Ino Y, Yamazaki-Itoh R, Shimada K, Iwasaki M, Kosuge T, Kanai Y, Hiraoka N: Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br J Canc 2013, 108:914-923.
    • 6. Droeser R, Zlobec I, Kilic E, Guth U, Heberer M, Spagnoli G, Oertli D, Tapia C: Differential pattern and prognostic significance of CD4+, FOXP3+ and IL-17+ tumor infiltrating lymphocytes in ductal and lobular breast cancers. BMC Canc 2012, 12:134.
    • 7. Ahmed MA, Aleskandarany MA, Rakha EA, Moustafa RZ, Benhasouna A, Nolan C, Green AR, Ilyas M, Ellis IO: A CD44(-)/CD24(+) phenotype is a poor prognostic marker in early invasive breast cancer. Breast Canc Res Treat 2011, 133:979-995.
    • 8. Ahmed MA, Al-Attar A, Kim J, Watson NF, Scholefield JH, Durrant LG, Ilyas M: CD24 shows early upregulation and nuclear expression but is not a prognostic marker in colorectal cancer. J Clin Pathol 2009, 62:1117-1122.
    • 9. Clevers H, Alarcon B, Wileman T, Terhorst C: The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol 1988, 6:629-662.
    • 10. Moebius U, Kober G, Griscelli AL, Hercend T, Meuer SC: Expression of different CD8 isoforms on distinct human lymphocyte subpopulations. Eur J Immunol 1991, 21:1793-1800.
    • 11. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, et al: Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006, 313:1960-1964.
    • 12. Kayser G, Schulte-Uentrop L, Sienel W, Werner M, Fisch P, Passlick B, Hausen AZ, Stremmel C: Stromal CD4/CD25 positive T-cells are a strong and independent prognostic factor in non-small cell lung cancer patients, especially with adenocarcinomas. Lung Canc 2012, 76:445-451.
    • 13. Berti E, Tomasini D, Vermeer MH, Meijer CJ, Alessi E, Willemze R: Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas. A distinct clinicopathological entity with an aggressive clinical behavior. Am J Pathol 1999, 155:483-492.
    • 14. Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW: The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Canc 2011, 105:93-103.
    • 15. Golay JT, Clark EA, Beverley PC: The CD20 (Bp35) antigen is involved in activation of B cells from the G0 to the G1 phase of the cell cycle. J Immunol 1985, 135:3795-3801.
    • 16. Mahmoud SM, Lee AH, Paish EC, Macmillan RD, Ellis IO, Green AR: The prognostic significance of B lymphocytes in invasive carcinoma of the breast. Breast Canc Res Treat 2012, 132:545-553.
    • 17. Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund LT: Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Canc Res 2008, 14:5220-5227.
    • 18. Milne K, Kobel M, Kalloger SE, Barnes RO, Gao D, Gilks CB, Watson PH, Nelson BH: Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One 2009, 4:e6412.
    • 19. McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM: REporting recommendations for tumor MARKer prognostic studies (REMARK). Nat Clin Pract Oncol 2005, 2:416-422.
    • 20. Aloysius MM, Hewavisenthi SJ, Bates TE, Rowlands BJ, Lobo DN, Zaitoun AM: Predictive value of tumor proliferative indices in periampullary cancers: Ki-67, mitotic activity index (MI) and volume corrected mitotic index (M/V) using tissue microarrays. World J Surg 2010, 34:2115-2121.
    • 21. Camp RL, Dolled-Filhart M, Rimm DL: X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Canc Res 2004, 10:7252-7259.
    • 22. Yu XQ, Baade PD, O'Connell DL: Conditional survival of cancer patients: an Australian perspective. BMC Canc 2012, 12:460.
    • 23. Luttges J, Schemm S, Vogel I, Hedderich J, Kremer B, Kloppel G: The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation. J Pathol 2000, 191:154-161.
    • 24. Nakao A, Harada A, Nonami T, Kaneko T, Takagi H: Clinical significance of carcinoma invasion of the extrapancreatic nerve plexus in pancreatic cancer. Pancreas 1996, 12:357-361.
    • 25. Takahashi T, Ishikura H, Motohara T, Okushiba S, Dohke M, Katoh H: Perineural invasion by ductal adenocarcinoma of the pancreas. J Surg Oncol 1997, 65:164-170.
    • 26. Hirai I, Kimura W, Ozawa K, Kudo S, Suto K, Kuzu H, Fuse A: Perineural invasion in pancreatic cancer. Pancreas 2002, 24:15-25.
    • 27. French JD, Weber ZJ, Fretwell DL, Said S, Klopper JP, Haugen BR: Tumor-associated lymphocytes and increased FoxP3+ regulatory T cell frequency correlate with more aggressive papillary thyroid cancer. J Clin Endocrinol Metab 2010, 95:2325-2333.
    • 28. Huh JW, Lee JH, Kim HR: Prognostic significance of tumor-infiltrating lymphocytes for patients with colorectal cancer. Arch Surg 2012, 147:366-372.
    • 29. Huang KH, Wang RF, Yang MH, Wu CW, Fang WL, Li AF, Chi CW, Kao HL: Advanced gastric cancer patients with lymphoid stroma have better survival than those without. J Surg Oncol 2013, 107:523-528.
    • 30. Flammiger A, Bayer F, Cirugeda-Kuhnert A, Huland H, Tennstedt P, Simon R, Minner S, Bokemeyer C, Sauter G, Schlomm T, et al: Intratumoral T but not B lymphocytes are related to clinical outcome in prostate cancer. APMIS 2012, 120:901-908.
    • 31. Hoos A, Cordon-Cardo C: Tissue microarray profiling of cancer specimens and cell lines: opportunities and limitations. Lab Invest 2001, 81:1331-1338.
    • 32. Henriksen KL, Rasmussen BB, Lykkesfeldt AE, Moller S, Ejlertsen B, Mouridsen HT: Semi-quantitative scoring of potentially predictive markers for endocrine treatment of breast cancer: a comparison between whole sections and tissue microarrays. J Clin Pathol 2007, 60:397-404.
    • 33. Goldstein NS, Hewitt SM, Taylor CR, Yaziji H, Hicks DG: Recommendations for improved standardization of immunohistochemistry. Appl Immunohistochem Mol Morphol 2007, 15:124-133.
  • No related research data.
  • No similar publications.

Share - Bookmark

Cite this article