Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Clinicopathology Significance of p53 and p63 Expression in Indonesian Cervical Squamous Cell Carcinomas

  • Romus, Ilhami (Department of Anatomical Pathology, Faculty of Medicine, Gadjah Mada University) ;
  • Triningsih, F.X. Ediati (Department of Anatomical Pathology, Faculty of Medicine, Gadjah Mada University) ;
  • Mangunsudirdjo, Sagiri (Department of Anatomical Pathology, Faculty of Medicine, Gadjah Mada University) ;
  • Harijadi, Ahmad (Department of Anatomical Pathology, Faculty of Medicine, Gadjah Mada University)
  • Published : 2013.12.31
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Abstract

Background: Human papilloma virus infection is associated with genesis and malignant potential of cervical cancer. E6 and E7 oncogens are known to bind to p53 and retinoblastoma gene products, abrogating their functions as tumor suppressors, leading to an abnormal cell cycle machinery. Roles of the p53 homolog p63 have also been postulated, E6 expression leading to TAp63b degradation allowing anchorage independent growth. Molecular studies correlated with clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and need to be clarified. Aim: To investigate expression of p53 and p63 in cervical squamous cell carcinomas in correlation with age, FIGO staging, morphology, and cancer cell proliferation. Materials and Methods: Expression of p53 and p63 immunohistochemical staining in a total of 56 paraffin-embedded tissues of cervical squamous cell carcinomas from Dr. Sardjito General Hospital Indonesia, was evaluated for correlation with clinicopathological parameters. The Mann-Whitney test was used to compare the percentage of p53 and p63 expression with patient age, FIGO staging and morphology and to compare mean p53 and p63 expression. The Spearman correlation test was applied to correlate p53 and p63 expression with that of Ki-67. A p-value of <0.05 was considered statistically significant. Results: There were significant associations between p53 expression with age (p=0.019) and FIGO staging (p=0.026), but not with with morphology or Ki-67 expression. There were no links between p63 expression and age, morphology, FIGO staging or Ki-67. Conclusions: This study indicated that p53 has a prognostic value in cervical squamous cell carcinomas given the relation with FIGO staging.

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References

  1. Aoky Y, Watanabe M, Sasaki M, et al (2001). Prognostic factors and failure pattern in lymph node- negative stage IB and II cervical carcinoma treated with radical hysterectomy and postoperative irradiation. Gynecol Obstet Invest, 52, 13-7. https://doi.org/10.1159/000052933
  2. Bosch FX, Manos MM, Munoz N, et al (1995). International Biological Study on Cervical Cancer (IBSCC) Study Group. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst, 87, 796-802. https://doi.org/10.1093/jnci/87.11.796
  3. Brinton LA, Tashima KT, Lehman HF, et al (1987). Epidemiology of cervical cancer by cell type. Cancer Res, 47, 1706-11
  4. Cho NM, Kim YB, Park TK, e al (2003). p63 and EGFR as prognostic predictors in stage IIB radiation-treated cervical squamous cell carcinoma. Gynecol Oncol, 91, 346-53. https://doi.org/10.1016/S0090-8258(03)00504-3
  5. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008, Int J Cancer, 127, 2893-917 https://doi.org/10.1002/ijc.25516
  6. FIGO Committee on Gynecologic Oncology (2000). Staging classifications and clinical practice guidelines of gynecologic cancers. Int J Gynecol Obstet, 70, 207-312. https://doi.org/10.1016/S0020-7292(00)00300-3
  7. Graflund M, Sorbe B, Bryne M, Karlsson M (2002). The prognostic value of a histologic grading system, DNA profile and MIB-1 expression in early stages of cervical squamous cell carcinoma. Int J Gynecol Cancer, 12, 149-57. https://doi.org/10.1046/j.1525-1438.2002.01088.x
  8. Jain D, Srinivasan R, Patel F, Gupta SK (2003). Evaluation of p53 and Bcl-2 expression as prognostic markers in invasive cervical carcinoma stage IIb/III patients treated by radiotherapy. Gynecol Oncol, 88, 22-8. https://doi.org/10.1006/gyno.2002.6838
  9. Khalifa YB, Teissier S, Tan MK, et al (2011). The Human Papillomavirus E6 Oncogene Represses a Cell Adhesion Pathway and Disrupts Focal Adhesion through Degradation of Tap63$\beta$ upon Transformation. Plos Pathogens, 7, 1-9.
  10. Khunamornpong S, Siriaunkgul S, Manusirivithaya S, et al (2006). Prognostic value of p53 expression in early stage cervical carcinoma treated by surgery. Asian Pac J Cancer Prev, 9, 48-52.
  11. Koh WJ, Panwala K, Greer B (2000). Adjuvant therapy for high risk, early stage cervical cancer. Semin Radiat Oncol, 10, 51-60. https://doi.org/10.1016/S1053-4296(00)80021-1
  12. Lu X (2004). p53, HPV and Cervical Cancer. Postgraduate Training Course in Reproductive health Geneva.
  13. Munger K (2002). The role of human papillomaviruses in human cancers. Front Biosci, 7, 641-9. https://doi.org/10.2741/munger
  14. Nygard JF, Skare GB, Thoresen SO (2002). The cervical cancer screening program in Norway,1992-2000: Changes in pap smear coverage and incidence of cervical cancer. J Med Screen, 9, 86-91. https://doi.org/10.1136/jms.9.2.86
  15. Quade BJ, Yang A, Wang Y, et al (2001). Expression of the p53 homologue p63 in early cervical neoplasia. Gynecol Oncol, 80, 24-9. https://doi.org/10.1006/gyno.2000.5953
  16. Shiohara S, Shiozawa T, Miyamoto T, et al (2005). Expression of cyclins, p53, and ki-67 in cervical squamous cell carcinomas: overexpression of cyclin A is a poor prognostic factor in stage Ib and II disease. Virchows Arch, 446, 626-33. https://doi.org/10.1007/s00428-005-1252-0
  17. Shirendeb U, Hishikawa Y, Moriyama S, et al (2009). Huma Papillomavirus infection and its possible correlation with p63 expression in cervical cancer in Japan, Mongolia, and Myanmar. Acta Histochem. Cytochem, 42, 181-90
  18. Tavassoli FA, Devilee P (2003 )(eds.)World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: IARC Press .
  19. Tiltman AJ (2005). The pathology of cervical tumours. Best Pract Res Clin Obstet Gynaecol, 19, 485-500, https://doi.org/10.1016/j.bpobgyn.2005.02.003
  20. Tsujita-Kyutoku M, Kiuchi K, Danbara N, et al (2003). p63 expression in normal human epidermis and epidermal appendages and their tumors. J Cutan Pathol, 30, 11-7. https://doi.org/10.1034/j.1600-0560.2003.300102.x
  21. Vasilescu F, Ceasu M, Tanase C, Stanculescu, et al (2009). p53, p63, Ki-67 assessment in HPV-induced cervical neoplasia. Rom J Morphol Embryol, 50, 357-61.
  22. Viczaino AP, Moreno V, Bosch FX, et al (2000). International trends in incidence of cervical cancer. II. Squamous-cell carcinoma. Int J Cancer, 86, 429-35 https://doi.org/10.1002/(SICI)1097-0215(20000501)86:3<429::AID-IJC20>3.0.CO;2-D
  23. Vosmik M, Laco J, Sirak I, Baranek M, et al (2013). Prognostic significance of HPV status and expression of selected markers (HER2/neu, EGFR, VEGF, CD34, p63, p53 and Ki-67) on outcome after (chemo) radiotherapy in patients with squamous cell carcinoma of uterine cervix. Pathol Oncol Res. [Epub ahead of print]
  24. Wang TY, Chen BF, Yang YC, et al (2001). Histologic and immunophenotypic classification of cervical carcinomas by expression of the p53 homologue p63: a study of 250 cases. Hum Pathol, 32, 479-86. https://doi.org/10.1053/hupa.2001.24324
  25. Zur Hausen (2002). Papillomavirusses and cancer: from basic studies to clinical application. Nat Rev Cancer, 2, 342-350. https://doi.org/10.1038/nrc798

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