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Quantitative Evaluation of Tumour - Associated Tissue Eosinophilia and Cyclo-oxegenase-2 Gene in Oral Cancer Patients with Assessment of Long Term Outcomes

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Pathology & Oncology Research

Abstract

Various histopathological parameters have been extensively studied for prognostication of oral cancer but the focus is now getting diverted towards the role of inflammatory mediators in cancer progression. The present study was undertaken to evaluate two such components of the inflammatory milieu, tumor-associated tissue eosinophilia (TATE) as well as Cyclo-oxygenase-2 (COX-2) gene expression, quantitatively in oral squamous cell carcinoma (OSCC) patients in relation to treatment outcomes and patterns of recurrence. A total of forty five patients with primary OSCC matching our inclusion criteria were selected for the study and followed up over a five year period. TATE was evaluated from the invasive front of the tumor using Haematoxylin and eosin (H & E) stained sections of histopathological specimens and graded as mild, moderate or intense. COX-2 gene expression was obtained from specimens using the reverse transcriptase - polymerase chain reaction (RT-PCR) method. A statistically significant association was observed between degree of TATE and locoregional recurrence (P < 0.001). The expression of COX-2 gene ranged from 0.4326 to 0.9998 and a higher mean COX-2 score was recorded in samples with intense degree of TATE followed by moderate and mild TATE. (P < 0.001). Using the t-test, the difference in mean COX-2 was found to be statistically significant (P < 0.001) between patients who developed locoregional recurrence and those who did not. The analysis of TATE may provide an indication of future recurrence at the time of diagnosis of OSCC. Also, the increased expression of COX-2 gene in OSCC strongly suggests its possible use as a chemopreventive/chemotherapeutic target.

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References

  1. Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45:309–316

    Article  PubMed  Google Scholar 

  2. Mignogna MD, Fedele S (2005) Oral cancer screening: 5 minutes to save a life. Lancet 365:1905–1906

    Article  PubMed  Google Scholar 

  3. Fedele S (2009) Diagnostic aids in the screening of oral cancer. Head Neck Oncol 1:5. doi:10.1186/1758-3284-1-5

    Article  PubMed  PubMed Central  Google Scholar 

  4. Massano J, Regateiro FS, Januário G, Ferreira A (2006) Oral squamous cell carcinoma: review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 102:67–76

    Article  PubMed  Google Scholar 

  5. Warnakulasuriya S (2010) Living with oral cancer: epidemiology with particular reference to prevalence and life-style changes that influence survival. Oral Oncol 46(6):407–410

    Article  PubMed  Google Scholar 

  6. Jerjes W, Upile T, Petrie A, et al. (2010) Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients. Head Neck Oncol. 20:2–9. doi:10.1186/1758-3284-2-9

    Google Scholar 

  7. Ford PJ, Farah CS (2013) Early detection and diagnosis of oral cancer: strategies for improvement. J Cancer Policy 1:e2–e7

    Article  Google Scholar 

  8. Bànkfalvi A, Piffkò J (2000) Prognostic and predictive factors in oral cancer: the role of the invasive tumour front. J Oral Pathol Med 29(7):291–298

    Article  PubMed  Google Scholar 

  9. Woolgar JA (2000) Histopathological prognosticators in oral and oropharyngeal squamous cell carcinoma. Oral Oncol 42(3):229–39F

    Article  Google Scholar 

  10. Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545

    Article  CAS  PubMed  Google Scholar 

  11. Mignogna MD, Fedele S, Lo Russo L, Lo Muzio L, Bucci E (2004) Immune activation and chronic inflammation as the cause of malignancy in oral lichen planus: is there any evidence? Oral Oncol 40(2):120–130

    Article  PubMed  Google Scholar 

  12. Tepper RI, Coffman RL, Leder P (1992) An eosinophil dependent mechanism for the antitumor effect of interleukin- 4. Science 257(5069):548–551

    Article  CAS  PubMed  Google Scholar 

  13. Astigiano S, Morandi B, Costa R, et al. (2005) Eosinophil granulocytes account for indoleamine 2,3-dioxygenase-mediated immune escape in human non-small cell lung cancer. Neoplasia 7(4):390–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fernández-Aceñero MJ, Galindo-GallegoM SJ, Aljama A (2000) Prognostic influence of tumor-associated eosinophilic infiltrate in colorectal carcinoma. Cancer 88(7):1544–1548

    Article  PubMed  Google Scholar 

  15. Kapp DS, LiVolsi VA (1983) Intense eosinophilic stromal infiltration in carcinoma of the uterine cervix: a clinicopathologic study of 14 cases. Gynecol Oncol 16(1):19–30

    Article  CAS  PubMed  Google Scholar 

  16. Cuschieri A, Talbot IC, Weeden S (2002) Influence of pathological tumour variables on long-term survival in resectable gastric cancer. Br J Cancer 86(5):674–679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pretlow TP, Keith EF, Cryar AK, et al. (1983) Eosinophil infiltration of human colonic carcinomas as a prognostic indicator. Cancer Res 43(6):2997–3000

    CAS  PubMed  Google Scholar 

  18. Spiegel GW, Ashraf M, Brooks JJS (2002) Eosinophils as a marker for invasion in cervical squamous neoplastic lesions. Int J Gynecol Pathol 21(2):117–124

    Article  PubMed  Google Scholar 

  19. Quaedvlieg PJF, Creytens DH, Epping GG, et al. (2006) Histopathological characteristics of metastasizing squamous cell carcinoma of the skin and lips. Histopathology 49(3):256–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Agarwal S, Wadhwa N, Gupta G (2002) Eosinophils as a marker for invasion in cervical squamous neoplastic lesions. Int J Gynecol Pathol 21(2):117–124

    Article  Google Scholar 

  21. Dorta RG, Landman G, Kowalski LP, Lauris JR, Latorre MR, Oliveira DT (2002) Tumour-associated tissue eosinophilia as a prognostic factor in oral squamous cell carcinomas. Histopathology 41:152–157

    Article  CAS  PubMed  Google Scholar 

  22. Horiuchi K, Mishima K, Ohsawa M, Sugimura M, Aozasa K (1993) Prognostic factors for well-differentiated squamous cell carcinoma in the oral cavity with emphasis on immunohistochemical evaluation. J Surg Oncol 53:92–96A

    Article  CAS  PubMed  Google Scholar 

  23. Tadbir AA, Ashraf MJ, Sardari Y (2009) Prognostic significance of stromal eosinophilic infiltration in oral squamous cell carcinoma. J Craniofac Surg. 20:287–289

    Article  PubMed  Google Scholar 

  24. Ercan I, Cakir B, Basak T, Ozdemir T, Sayin I, Turgut S (2005) Prognostic significance of stromal eosinophilic infiltration in cancer of the larynx. Otolaryngol Head Neck Surg. 132:869–873

    Article  PubMed  Google Scholar 

  25. Alrawi SJ, Tan D, Stoler DL, et al. (2005) Tissue eosinophilic infiltration: a useful marker for assessing stromal invasion, survival and locoregional recurrence in head and neck squamous neoplasia. Cancer J 11:217–225

    Article  PubMed  Google Scholar 

  26. Said M, Wiseman S, Yang J, et al. (2005) Tissue eosinophilia: a morphologic marker for assessing stromal invasion in laryngeal squamous neoplasms. BMC Clin Pathol 5:1–8

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sassler AM, McClatchey KD, Wolf GT, Fisher SG (1995) Eosinophilic infiltration in advanced laryngeal squamous cell carcinoma. Laryngoscope 105:413–416

    Article  CAS  PubMed  Google Scholar 

  28. Lowe D, Fletcher CDM (1984) Eosinophilia in squamous cell carcinoma of the oral cavity, external genitalia and anusclinical correlations. Histopathology 8(4):627–632

    Article  CAS  PubMed  Google Scholar 

  29. Falconieri G, Luna MA, Pizzolitto S, DeMaglio G, Angione V, Rocco M (2008) Eosinophil-rich squamous carcinoma of the oral cavity: a study of 13 cases and delineation of a possible new microscopic entity. Ann Diagn Pathol 12:322–327

    Article  PubMed  Google Scholar 

  30. Goldsmith MM, Belchis DA, Cresson DH, Merritt WD, Askin FB (1992) The importance of the eosinophil in head and neck cancer. Otolaryngol Head Neck Surg. 106:27–33

    CAS  PubMed  Google Scholar 

  31. Wong DTW, Bowen SM, Elovic A, Gallagher GT, Weller PF (1999) Eosinophil ablation and tumor development. Oral Oncol 35:496–501

    Article  CAS  PubMed  Google Scholar 

  32. Oliveira DT, Biassi TP, Faustino SE, Carvalho AL, Landman G, Kowalski LP (2012) Eosinophils may predict occult lymph node metastasis in early oral cancer. Clin Oral Investig 16(6):1523–1528

    Article  CAS  PubMed  Google Scholar 

  33. Davoine F, Sim A, Tang C, et al. (2013) Eosinophils in human oral squamous carcinoma; role of prostaglandin D2. J Inflamm (Lond) 10(1):4

    Article  CAS  Google Scholar 

  34. Mohammad S, Ram H, Gupta PN, Husain N, Bhatt MLB (2011) Overexpression of COX-2 in oral squamous cell carcinoma patients undergoing chemoradiotherapy. Natl J Maxillofac Surg 2(1):17–21

    Article  PubMed  PubMed Central  Google Scholar 

  35. Itoh S, Matsui K, Furuta I, Takano Y (2003) Immunohistochemical study on over expression of cyclooxygenase-2 in squamous cell carcinoma of the oral cavity: its importance as a prognostic predictor. Oral Oncol 39:829–835

    Article  CAS  PubMed  Google Scholar 

  36. Pandey M, Prakash O, Santhi WS, Soumithran S, Pillai RM (2008) Overexpression of COX-2 gene in oral cancer is independent of stage of disease and degree of differentiation. Int J Oral Maxillofac Surg 37:379–383

    Article  CAS  PubMed  Google Scholar 

  37. Sharma M, Sah P, Sharma SS, Radhakrishnan R (2013) Molecular changes in invasive front of oral cancer. J Oral Maxillofac Pathol 17(2):240–247

    Article  PubMed  PubMed Central  Google Scholar 

  38. Oliveira DT, Tjioe KC, Assao A, et al. (2009) Tissue eosinophilia and its association with tumoral invasion of oral cancer. Int J Surg Pathol 17(3):244–249

    Article  Google Scholar 

  39. Lorena SC, Dorta RG, Landman G, Nonogaki S, Oliveira DT (2003) Morphometric analysis of the tumor associated tissue eosinophilia in the oral squamous cell carcinoma using different staining techniques. Histol Histopathol 18(3):709–713

    CAS  PubMed  Google Scholar 

  40. Tortora G, Caputo R, Damiano V, et al. (2003) Combination of a selective COX-2 inhibitor with epidermal growth factor receptor, tyrosine kinase inhibitor ZD1839 and protein kinase A antisense causes cooperative antitumor and antiangiogenic effect. Clin Cancer Res 9:1566–1572

    CAS  PubMed  Google Scholar 

  41. Kao J, Genden EM, Chen CT, et al. (2011) Phase 1 trial of concurrent erlotinib, celecoxib, and reirradiation for recurrent head and neck cancer. Cancer 117(14):3173–3181

    Article  CAS  PubMed  Google Scholar 

  42. Uddin MJ, Crews BC, Ghebreselasie K, et al. (2011) Fluorinated COX-2 inhibitors as agents in PET imaging of inflammation and cancer. Cancer Prev Res (Phila) 4(10):1536–1545

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Oral Medicine, Diagnosis and Radiology, M.S. Ramaiah Dental College & Hospital, MSRIT Post, New BEL Road, Bangalore, India

    N. Rakesh & Kuhu Majumdar

  2. Department of Oral Medicine, Diagnosis and Radiology, DAPM R.V. Dental College and Hospital, Bangalore, India

    Asha Iyengar

  3. Department of Oral Pathology and Microbiology, M.S.Ramaiah Dental College & Hospital, Bangalore, India

    G. S. Vidya

  4. Department of Biotechnology, M.S. Ramaiah Institute of Technology, Bangalore, India

    S. S. Shantha Kumar

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  1. N. Rakesh
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  2. Asha Iyengar
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  3. Kuhu Majumdar
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  4. G. S. Vidya
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  5. S. S. Shantha Kumar
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Correspondence to N. Rakesh.

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Rakesh, N., Iyengar, A., Majumdar, K. et al. Quantitative Evaluation of Tumour - Associated Tissue Eosinophilia and Cyclo-oxegenase-2 Gene in Oral Cancer Patients with Assessment of Long Term Outcomes. Pathol. Oncol. Res. 22, 385–392 (2016). https://doi.org/10.1007/s12253-015-0016-7

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  • DOI: https://doi.org/10.1007/s12253-015-0016-7

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