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Prognostic Significance of Two Dimensional AgNOR Evaluation in Local Advanced Rectal Cancer Treated with Chemoradiotherapy

  • Gundog, Mete (Departmentof Radiation Oncology, Kayseri Education and Research Hospital, University of Erciyes) ;
  • Yildiz, Oguz G (Departmentof Radiation Oncology, Kayseri Education and Research Hospital, University of Erciyes) ;
  • Imamoglu, Nalan (Department of Basic Pharmaceutical Sciences, Kayseri Education and Research Hospital, University of Erciyes) ;
  • Aslan, Dicle (Departmentof Radiation Oncology, Kayseri Education and Research Hospital, University of Erciyes) ;
  • Aytekin, Aynur (Department of Radiation Oncology, Kayseri Education and Research Hospital, University of Erciyes) ;
  • Soyuer, Isin (Department of Pathology, Kayseri Education and Research Hospital, University of Erciyes) ;
  • Soyuer, Serdar (Departmentof Radiation Oncology, Kayseri Education and Research Hospital, University of Erciyes)
  • Published : 2016.01.11

Abstract

The prognostic significance of AgNOR proteins in stage II-III rectal cancers treated with chemoradiotherapy was evaluated. Silver staining was applied to the $3{\mu}m$ sections of parafin blocked tissues from 30 rectal cancer patients who received 5-FU based chemoradiotherapy from May 2003 to June 2006. The microscopic displays of the cells were transferred into the computer via a video camera. AgNOR area (nucleolus organizer region area) and nucleus area values were determined as a nucleolus organizer regions area/total nucleus area (NORa/TNa). The mean NORa/TNa value was found to be $9.02{\pm}3.68$. The overall survival and disease free survival in the high NORa/TNa (>9.02) patients were 52.2 months and 39.4 months respectively, as compared to 100.7 months and 98.4 months in the low NORa/TNa (<9.02) cases. (p<0.001 and p<0.001 respectively). In addition, the prognosis in the high NORa/TNa patients was worse than low NORa/TNa patients (p<0.05). In terms of overall survival and disease-free survival, a statistically significant negative correlation was found with the value of NORa/TNa in the correlations tests. Cox regression analyses demostrated that overall survival and disease-free survival were associated with lymph node status (negative or positive) and the NORa/TNa value. We suggest that two-dimensional AgNOR evaluation may be a safe and usable parameter for prognosis and an indicator of cell proliferation instead of AgNOR dots.

Keywords

References

  1. Adachi Y, Kido A, Mori M, et al (1995). Nucleolar DNA content and nucleolar organizer regions in colorectal cancer. J Surg Oncol, 59, 177-80 https://doi.org/10.1002/jso.2930590308
  2. Aubele M, Biesterfeld S, Derenzini M, et al (1994). Guidelines of AgNOR quantitation. Zentralbl Pathol, 140, 107-8
  3. Boring CC, Squires, Tong T (1993). Cancer Statistics. CA Cancer J Clin, 43, 7-26 https://doi.org/10.3322/canjclin.43.1.7
  4. Cabrini R, Schwint A, Mendez A, et al (1992). Morphometri study of nucleolar organizer regions in human oral normal mucosa, papilloma and squamous cell carcinoma. J Oral Pathol Med, 21, 257-9.
  5. Chen Maohuai MD, CK Lee J, Lo S (2003). Argyrophilic Nuclear Organizer Regions in Nasopharyngeal Carsinoma and Paraneoplastik Epithelia. Head Neck, 25, 395-9 https://doi.org/10.1002/hed.10222
  6. Chern JH, Lee YC, Yang MH, et al (1997). Usefulness of AgNOR score in differentiating bening from malignant pulmonary aspiration cytology. Acta Cytol, 41, 393-8 https://doi.org/10.1159/000332530
  7. Cucer N, Imamoglu N, Tozak H, et al (2007). Two-dimensional agnor evaluation as a prognostic variable in urinary bladder carcinoma, a different approach via total agnor area/nucleus area per cell. Micron, 38, 674-9 https://doi.org/10.1016/j.micron.2006.08.002
  8. Demirtas H, Imamoglu N, Donmez H, et al (2001). Condensed chromatin surface and NORs surface enhancement in mitogen-stimulated lymphocytes of Down syndrome patients. GenParis, 44, 77-82.
  9. Derenzini M, Nardi F, Farabegoli F, et al (1989). Disrubition of silver-stained interphase nucleolar organizer regions as a parameter to distinguish neoplastic from nonneoplastic reactive cell in human effusions. Acta Cytol, 33, 491-8
  10. Derenzini M, Pession A, Trere D (1990). Quantity of nucleolar silver-stained proteins is related to proliferating activity in cancer cells. Lab Invest. 63, 137-40
  11. Derenzini M, Romagnoli T, Mingazzini P, et al (1988). Interphasic nucleolar organizer region distribution as a diagnostic parameter to differentiate bening from malignant epithelial tumors of human intestine. Virchows Arch, 54, 334-40
  12. Derenzini M, Trere D, Mambelli V, et al (1990). Diagnostic value of silver-stained interphasic nucleolar organizer in the breast tumors. Ultrastruct Pathol, 14, 233-45 https://doi.org/10.3109/01913129009076127
  13. Eser S, Yakut C, Ozdemir R, et al (2010). Cancer incidence rates in Turkey in 2006. Asian Pac J Cancer, 11, 1731-9
  14. Fonseca I, Soares J (1993). Adenoid cystic carcinoma a study of nucleolar organizer regions (AgNORs) counts and their relation to prognosis. J Pathol, 169, 255-258 https://doi.org/10.1002/path.1711690213
  15. Gimenes-Mas J, Gallego-Calvo P, Sanz-Moncasi P, et al (1995). AgNOR evaluation by image processing methods. Staining modifications and results in 126 invasive ductal breast carsinomas. Anal Quant Cytol Histol, 18, 9-18
  16. Gordon K.C, Bancoft JD, Stevens A, et al Turner DR (Eds) (1990). Theory and practise of histological tecniques. 3rd ed. Churchill Livingstone, London.
  17. Gunderson & Teper (2012). Clinical radiation oncology (3th edition) Saunders, Philadelphia, pp. 1113-1114
  18. Lindner LE (1993). Improvements in the silver-staining technique for nucleolar organizer regions (AgNOR). J Histochem Cytochem, 41, 439-445 https://doi.org/10.1177/41.3.8429207
  19. Losi L, DiGregorio C, Fante R, et al (1995). Argyrophilic nucleolar organizer regions and bromodeoxyuridine and 3[H] -thymidine labelling indices in colorectal cancer. Cell Prolif, 28, 471-80 https://doi.org/10.1111/j.1365-2184.1995.tb00086.x
  20. Nishi Y, Takano Y, Kakita A (1994). Analyses of PCNA and AgNOR on advanced colorectal cancer as predictive indicators of the prognosis. Nippon Geka Gakkai Zasshi, 95, 797-806
  21. Ofner (2000). In situ standardised AgNOR analysis, a simplified method for routine use to determine prognosis and chemthrapy efficiency in colorectal adenocarcinoma. Micron, 31, 161-4 https://doi.org/10.1016/S0968-4328(99)00073-6
  22. Ofner D, Bier B, Heinrichs S, et al (1996). Demonstration of silver-stained nucleolar organizer region associated proteins (AgNORs) after wet autoclave pretreatment in breast carsinoma, correlation to tumour stage and long-term survival. Breast Cancer RES Treat, 39, 165-76 https://doi.org/10.1007/BF01806183
  23. Ofner D, Totsch M, Sandbicher P, et al (1990). Silver stained nucleolar organizer regions (Ag-NORs) as a predictor of prognosis in colonic cancer. J Pathol, 162, 43-49 https://doi.org/10.1002/path.1711620109
  24. Pich A, Chiusa L, Margaria E (2000). Prognostik relevance of AgNORs in tumor pathology. Micron, 31, 133-141 https://doi.org/10.1016/S0968-4328(99)00070-0
  25. Piffko J, Bankfalvi A, Ofner D, et al (1997). Prognostic value of histobiological factors (malignancy grading and AgNOR content) assessed at the invasive tumor front of oral squamous cell carsinomas. Br J Cancer, 75, 1543-6 https://doi.org/10.1038/bjc.1997.263
  26. Piffko J, Bankfalvi A, Ofner D, et al (1997). Standardized demonstration of silver-stained nucleolar organizer regions, associated proteins in archival oral squamous cell carsinomas and adjacent non-neoplastic mucusa. Mod Pathol, 10, 98-104
  27. Ploton D, Menager M, Jeannneson P, et al (1986). Improvement in staining and in the visualization of tne argyrophilic proteins of the nucleolar organizer region at the optical level. Histon chem J, 18, 5-14
  28. Raskov H, Pommergand HC, Burcharth J, et al (2014). Colorectal carcinogenesis update and perspective. World J Gastroenterol, 20, 18151-64 https://doi.org/10.3748/wjg.v20.i48.18151
  29. Senija Eminovic-Behrem, Zlatko Trobonjaca, Mladen Petrovecki, et al (2000). Prognostic significance of dna ploidy pattern and nucleolar organizer regions(AgNOR) in colorectal cancer. Croatian Medical Journal, 41, 154-8
  30. Shiro Nakae, Takeshi Nakamura, Ryuichiro Ikegawa, et al (1998). Evaluation of argyrophilic nucleolar organizer region and proliferating cell nuclear antigen in colorectal cancer. J Surgical Oncol, 69, 28-35 https://doi.org/10.1002/(SICI)1096-9098(199809)69:1<28::AID-JSO6>3.0.CO;2-M
  31. Sideris M, Papagrigoriadis S (2014). Molecular biomarkers and classification models in the evaluation of the prognosis of colorectal cancer. Anticancer Res, 34, 2061-8
  32. Suto T, Sugai T, Nakamura S, et al (1998). Assessment of the expression of p53, MIB-1 (Ki-67 antigen) and argyrophilic nucleolar organizer regions in carsinoma of the extrahepatic bile duct. Cancer, 82, 86-95 https://doi.org/10.1002/(SICI)1097-0142(19980101)82:1<86::AID-CNCR10>3.0.CO;2-9
  33. Trere D (1994). Technical and methodological aspects of silver staining and measurement of nucleolar organizer region (NOR). Zentralbl Pathol, 140, 11-14
  34. Trere D, Farabegoli F, Cancellieri A, et al (1991). AgNOR area in interphase nuclei of human tumours correlates with the proliferative activity evaluated by bromodeoxyuridine labelling and KI-67 immunostaining. J Pathol, 165, 53-59 https://doi.org/10.1002/path.1711650109
  35. Trere D, Pession A, Derenzini M (1989). The silver stained proteins of interphasic nucleolar organizer regions as a parameter of cell duplication rate. Exp Cell Res, 184, 131-7 https://doi.org/10.1016/0014-4827(89)90371-6
  36. Wai Pak M, Fai To K, Huai Chen M, et al (2000). Morphometricanalysis of argyrophilic nucleolar organizer regions (AgNORs) in Nasopharyngeal Carsinoma. Head Neck, 22, 760-4 https://doi.org/10.1002/1097-0347(200012)22:8<760::AID-HED3>3.0.CO;2-P

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