- Volume 13 Issue 12
DOI QR Code
Expression of P-glycoprotein is Positively Correlated with p53 in Human Papilloma Virus Induced Squamous Intraepithelial Lesions of Uterine Cervix: Poor Prognosis Association
- Singh, Madhulika (Proteomics Laboratory, Indian Institute of Toxicology Research (Council of Scientific and Industrial Research)) ;
- Singh, Uma (Department of Obstetrics and Gynecology, Chhatrapati Shahuji Maharaj Medical University) ;
- Mathur, Neeraj (Department of Epidemiology, Indian Institute of Toxicology Research (Council of Scientific and Industrial Research)) ;
- Shukla, Yogeshwer (Proteomics Laboratory, Indian Institute of Toxicology Research (Council of Scientific and Industrial Research))
- Published : 2012.12.31
This study was conducted to assess the predictive value of p-glycoprotein (p-gp) and p53 immunoexpression in human papillomavirus (HPV) infected cases of cervical dysplasia. Expression of both p-gp and p53 proteins was detected in cervical smears from 177 squamous intraepithelial lesions (SIL) cases along with 183 "atypical squamous cells of unknown significance" (ASCUS) and 150 normal cases. HPV 16 and 18 infection was detected by polymerase chain reaction using type-specific primers for HPV sub-types. There were no significant detectable p53 and p-gp expression in the normal cervix smears (p>0.05). In the ASCUS group 10 cases were positive for both p53 and p-gp immunoreactivity. In cervical dysplasia cases, p53 was positive in 86 (48.58%) while p-gp was positive in 93 (52.54%) and the two markers showed a highly significant correlation (r=0.92, p<0.001). Expression of p53 and p-gp was associated with grade of SIL (p<0.001). A positive correlation between the presence of HPV and expression of proteins p53 and p-gp in smears of patients with cervical lesions was also noted (p<0.001). Thus, p53 and p-gp immunostaining in cervical smears may act as an auxiliary biomarker for detection of HPV-associated cervical lesions. Additionally, a significant positive correlation between ascending grades of SIL and labeling indices of markers suggests that p53 and p-gp can be used as an adjunct to cytomorphological interpretation of conventional cervical Pap smears.
Cervical dysplasia;human papilloma virus;p;glycoprotein;p53;SIL/CIN;cervical smear
- Wattel E, Preudhomme C, Hecquet B, et al (1994). p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood, 84, 3148-57.
- Yakirevich E, Sabo E, Naroditsky I, et al (2006). Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas. Gynecol Oncol, 100, 152-9. https://doi.org/10.1016/j.ygyno.2005.08.050
- Perego P, Giarola M, Righetti SC, et al (1996). Association between cisplatin resistance and mutation of p53 gene and reduced bax expression in ovarian carcinoma cell systems. Cancer Res, 56, 556-62.
- Pinedo HM, Giaccone G (1995). P-glycoprotein--a marker of cancer-cell behavior. N Engl J Med, 333, 1417-9. https://doi.org/10.1056/NEJM199511233332111
- Ralhan R, Narayan M, Salotra P, Shukla NK, Chauhan SS (1997). Evaluation of P-glycoprotein expression in human oral oncogenesis: correlation with clinicopathological features. Int J Cancer, 72, 728-34. https://doi.org/10.1002/(SICI)1097-0215(19970904)72:5<728::AID-IJC4>3.0.CO;2-U
- Ralhan R, Swain RK, Agarwal S, et al (1999). P-glycoprotein is positively correlated with p53 in human oral pre-malignant and malignant lesions and is associated with poor prognosis. Int J Cancer, 84, 80-5. https://doi.org/10.1002/(SICI)1097-0215(19990219)84:1<80::AID-IJC15>3.0.CO;2-G
- Righetti SC, Della Torre G, Pilotti S, et al (1996). A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma. Cancer Res, 56, 689-93.
- Riou G, Barrois M, Prost S, et al (1995). The p53 and mdm-2 genes in human testicular germ-cell tumors. Mol Carcinog, 12,124-31. https://doi.org/10.1002/mc.2940120303
- Rusch V, Klimstra D, Venkatraman E, et al (1995). Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer. Cancer Res, 55, 5038-42.
- Sampath J, Sun D, Kidd VJ, et al (2001). Mutant p53 cooperates with ETS and selectively up-regulates human MDR1 not MRP1. J Biol Chem, 276, 39359-67. https://doi.org/10.1074/jbc.M103429200
- Scheffner M, Werness BA, Huibregste JM, Levin AJ, Howley PM (1990). The E6 oncoprotein encoded papillomavirus types 16 and 18 promotes the degradation of p53. Cell, 63, 1129-36. https://doi.org/10.1016/0092-8674(90)90409-8
- Schlecht NF, Platt RW, Duarte-Franco E, et al (2003). Human papillomavirus infection and time to progression and regression of cervical intraepithelial neoplasia. J Natl Cancer Inst, 95, 1336-43. https://doi.org/10.1093/jnci/djg037
- Schneider J, Rubio MP, Barbazan MJ, et al (1994). P-glycoprotein, HER-2/neu, and mutant p53 expression in human gynecologic tumors. J Natl Cancer Inst, 86, 850-55. https://doi.org/10.1093/jnci/86.11.850
- Singh M, Srivastava S, Singh U, Mathur N, Shukla Y (2009). Co-expression of p53 and Bcl-2 proteins in human papillomavirus-induced premalignant lesions of the uterine cervix: correlation with progression to malignancy. Tumour Biol, 30, 276-85. https://doi.org/10.1159/000259911
- Solomon D, Davey D, Kurman R, et al (2002). Forum Group Members; Bethesda 2001 Workshop. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA, 287, 2114-19. https://doi.org/10.1001/jama.287.16.2114
- Stoler MH (2000). Human papillomaviruses and cervical neoplasia: a model for carcinogenesis. Int J Gynecol Pathol, 19, 16-28. https://doi.org/10.1097/00004347-200001000-00004
- van den Brule AJ, Snijders PJ, Raaphorst PM, et al (1992). General primer polymerase chain reaction in combination with sequence analysis for identification of potentially novel human papillomavirus genotypes in cervical lesions. J Clin Microbiol, 30, 1716-21.
- Chin KV, Ueda K, Pastan I, Gottesman MM (1992). Modulation of activity of the promoter of the human MDR1 gene by Ras and p53. Science, 255, 459-62. https://doi.org/10.1126/science.1346476
- Evans MF, Adamson CS, Papillo JL, et al (2006). Distribution of human papillomavirus types in ThinPrep Papanicolaou tests classified according to the Bethesda 2001 terminology and correlations with patient age and biopsy outcomes. Cancer, 106, 1054-64. https://doi.org/10.1002/cncr.21664
- Ferlay J, Bray F, Pisani P, Parkin DM, eds. Globocan 2002: Cancer Incidence, Mortality, and Prevalence Worldwide, Version 2.0. Lyon, France: IARC Press; 2004. IARC Cancer Base No. 5.
- Hayashida M, Nakajima H, Ishimaru T, Yamabe T (1997). Immunohistochemical expression of P-glycoprotein in cases of uterine cervical cancer. Int J Clin Oncol, 2, 103-10. https://doi.org/10.1007/BF02488881
- Helland A, Holm R, Kristensen G, et al (1993). Genetic alterations of the TP53 gene, p53 protein expression and HPV infection in primary cervical carcinomas. J Pathol, 171, 105-14. https://doi.org/10.1002/path.1711710207
- Huang LW, Chou YY, Chao SL, Chen TJ, Lee TTY (2001). p53 and p21 Expression in Precancerous Lesions and Carcinomas of the Uterine Cervix: Overexpression of p53 Predicts Poor Disease Outcome. Gynecol Oncol, 83, 348-54. https://doi.org/10.1006/gyno.2001.6397
- Jain V, Das SN, Luthra K, Shukla NK, Ralhan R (1997). Differential expression of multidrug-resistance-gene product, p-glycoprotein in normal, dysplastic and malignant oral mucosa in India. Int J Cancer, 74, 128-33. https://doi.org/10.1002/(SICI)1097-0215(19970220)74:1<128::AID-IJC21>3.0.CO;2-A
- Johnstone RW, Ruefli AA, Tainton KM, Smyth MJ (2000). A role for P-glycoprotein in regulating cell death. Leuk Lymphoma, 38, 1-11.
- Kent A (2010). HPV Vaccination and Testing. Reviews in Obstetrics and Gynecology, 3, 33-4.
- Konishi I, Nanbu K, Mandai M, et al (1998). Tumor response to neoadjuvant chemotherapy correlates with the expression of P-glycoprotein and PCNA but not GST-pi in the tumor cells of cervical carcinoma. Gynecol Oncol, 70, 365-71. https://doi.org/10.1006/gyno.1998.5077
- Linn SC, Honkoop AH, Hoekman K, et al (1996). p53 and P-glycoprotein are often co-expressed and are associated with poor prognosis in breast cancer. Br J Cancer, 74, 63-8. https://doi.org/10.1038/bjc.1996.316
- Nair P, Jayaprakash PG, Nair MK, Pillai MR (2000). Telomerase, p53 and human papillomavirus infection in the uterine cervix. Acta Oncol, 39, 65-70. https://doi.org/10.1080/028418600430996
- Oh MJ, Choi JH, Lee YH, et al (2004). Mutant p53 protein in the serum of patients with cervical carcinoma: correlation with the level of serum epidermal growth factor receptor and prognostic significance. Cancer Lett, 203, 107-12. https://doi.org/10.1016/j.canlet.2003.09.025
- Park CS, Soo IS, Song SY, et al (1999). An immunohistochemical analysis of heat shock protein 70, p53 and estrogen receptor status in carcinoma of the uterine cervix. Gynecol Oncol, 74, 53-60. https://doi.org/10.1006/gyno.1999.5429
- Park YB, Kim HS, Oh JH, et al (2001). The co-expression of p53 protein and P-glycoprotein is correlated to a poor prognosis in osteosarcoma. Int Orthop, 24, 307-10. https://doi.org/10.1007/s002640000196
- Bahnassy AA, Zekri AR, Madbouly MS, et al (2006). The correlation between FHIT, P53 and MMR genes in human papillomavirus-associated cervical carcinoma. J Egypt Natl Canc Inst, 18, 191-202.
- Bremer GL, Tieboschb A TMG, Van der putten HWHM, Haan JD, Arends JW (1995). P53 tumor suppressor gene protein expression in cervical cancer: relationship to prognosis. Eur J Obstet Gynecol Reprod Biol, 63, 55-9. https://doi.org/10.1016/0301-2115(95)02225-V
- Canavan TP, Doshi NR (2000). Cervical cancer. Am Fam Physician, 61, 1369-76.
- Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells vol.15, pp.3, 2014, https://doi.org/10.7314/APJCP.2014.15.3.1403