Detention of HPV L1 Capsid Protein and hTERC Gene in Screening of Cervical Cancer

Document Type: Original Article

Authors

Department of Gynecology and Obstetrics, Shenzhen Hospital of Beijing University, Shenzhen 518036, China

Abstract

 

Objective(s):
To investigate the expression of human papilloma virus (HPV) L1 capsid protein, and human telomerase RNA component (hTERC) in cervical cancer and the role of detection of both genes in screening of cervical cancer.
 
Materials and Methods:
A total of 309 patients were recruited and cervical exfoliated cells were collected. Immunocytochemistry was employed to detect HPV L1 capsid protein, and fluorescent in situ hybridization (FISH) was performed to detect the hTERC.
Results:
The expression of HPV L1 capsid protein reduced with the increase of the histological grade of cervical cells and was negatively related to the grade of cervical lesions. However, the expression of hTERC increased with the increase of the histological grade and positively associated with the grade of cervical lesions. The proportion of patients with L1(-)/hTERC(+) was higher in patients with histological grade of CIN2 or higher than that in those with histological grade of CIN1. The L1(+)/hTERC(-) and L1(-)/hTERC(-) were negatively related to the grade of cervical lesions. L1(-)/hTERC(+) was positively associated with the grade of cervical lesions. The L1/hTERC ratio increased. The negative predictive value of both HPV L1 and hTERC was higher than that of HPV L1 or hTERC, but there was no marked difference in the screening efficacy of cervical cancer among HPV L1, hTERC and HPV L1+hTERC.
Conclusion:
HPV L1 capsid protein and hTERC gene may serve as markers for the early diagnosis and prediction of cervical lesions. The increase in L1/hTERC ratio reflects the progression of cervical lesions to a certain extent.

Keywords


1. Dehn D, Torkko KC, Shroyer R. Human papillomavirus testing and molecular markers of cervical dysplasia and carcinoma. Cancer 2007; 111:1-14.

2. Yoshida T, Sano T, Kanuma T, Owada N, Sakurai S, Fukuda T, et al. Immunochemical analysis of HPV L1 capisid protein and p16 protein in liquid-based cytology samples from uterine cervical lesions. Cancer 2008; 114:83-88.

Screening Mark of Cervical Cancer Bin H et al

Iran J Basic Med Sci, Vol. 16, No. 6, Jun 2013

 

801

3. Khadem GN, Meshkat Z. Preventive and therapeutic vaccines against human papillomaviruses associated cervical cancers. Iran J Basic Med Sci 2012; 15:585-601.

4. Melnikow J, Nuovo J, Willan AR, Chan BK, Howell LP. Natural history of cervical quamous intraepithelial lesions: a meta-analysis. Obstet Gynecol 1998; 92:727-735.

5. Huh WK. Human papillomavirus infection: a concise review of natural history. Obstet Gynecol 2009; 114:139-143.

6. Roden R, Wu TC. How will HPV vaccines affect cervical cancer? Nat Rev Cancer 2006; 6:753-763.

7. Rauber D, Mehlhorn G, Fasching PA, Beckmann MW, Ackermann S. Prognostic significance of the detection of the human papillomavirus L1 protein in smears of mild to moderate cervical intraepithelial lesions. Eur J Obste Gynecol Reprod Biol 2008; 140:58-262

8. Lee H, Lee KJ, Jung CK, Hong JH, Lee YS, Choi YJ, et al. Expression of HPV L1 capsid protein in cervical specimens with HPV infection. Diagn Cytopathol 2008; 36(12):864-867.

9. Arafa M, Boniver J, Delvenne P. Detection of HPV-induced cervical(pre)neoplastic lesions.A tissue microarry(TMA) study. Appl Immunohistochem Mol Morphol 2008; 6:422-432.

10. Hilfrich R, Hariri J. Prognostic relevance of human papillomavirus L1 capsid protein detection within mild and moderate dysplastic lesions of the cervix uteri in combination with p16 biomarker. Anal Quant Cytol Histol 2008; 3:78-82.

11. Hopman AH, Theelen W, Hommelberg PP, Kamps MA, Herrington CS, Morrison LE, et al. Genomic intergration of oncogenic HPV and gain of the human telomerase gene TERC at 3q26 are strongly associated events in the progression of uterine cervical dysplasia to invasive cancer. J Pathol 2006; 10:412-419.

12. Nowak T, Januszkiewicz D, Zawada M, Pernak M, Lewandowski K, Rembowska J, et al. Amplification of hTERT and hTERC genes in leukemic cells with high expression and activity of telomerase. Oncol Rep 2006; 16:301-305.

13. Cao Y, Bryan TM, Reddel RR. Increased copy number of the TERT and TERC telomerase subunit genes in cancer cells. Cancer Sci 2008; 99:l092-l099.

14. Kawai K, Yaginuma Y, Tsuruoka H, Griffin M, Hayashi H, Ishikawa M. Telomerase activity and human papillomavirus (HPV) infection in human uterine cervical cancers and cervical smears. Eur J Cancer 1998; 34:2082-2086.

15. Ferenzy A, Franco E. Persistent human papillomavirus infection and cervical neoplasia. Lancet Oncol 2002; 3:11-6.

16. James MA, Lee JH, Klingelhutz ZM. Human papillomavirus type 16 E6 activates NF-kappaB, induces cIAP-2 expression, and protects against apoptosis in a PDZ binding motif-dependent manner. J Virol 2006; 80:5301-5307.

17. Ferber MJ, Montoya DP, Yu C, Aderca I, McGee A, Thorland EC. Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers. Oncogene 2003; 22:3813-3820.

18. Heselmeyer-Haddad K, Janz V, Castle PE, Chaudhri N, White N, Wilber K, et al. Detection of genomic amplification of the human telomerase gene (hTERC) in cytologic specimens as a genetic test for the diagnosis of cervical dysplasia. Am J Pathol 2003; 163:1405-16.

19. Caraway NP, Khanna A, Dawlett M, Guo M, Guo N, Lin E, Katz RL. Gain of the 3q26 region incervicovaginal liquid-based pap preparations is associated with squamous intraepithelial lesions and squamous cell carcinoma. Gynecol Oncol 2008; 110:37-42.

20. Münger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, et al. Mechanisms of human papillomavirus-induced oncogenesis. J Virol 2004; 78:1145l-11460.

22. Rao PH, Arias-Pulido H, Lu XY, Harris CP, Vargas H, Zhang FF, et al. Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes in cervical carcinoma. BMC Cancer 2004; 4:5.

23. Wilting SM, de Wilde J, Meijer CJ, Berkhof J, Yi Y, van Wieringen WN, et al. Integrated genomic and transcriptional profiling dentifies chromosomal loci with altered gene expression in cervical cancer. Genes Chromosomes Cancer 2008; 47:890-905.

23. Sugita M, Tanaka N, Davidson S, Sekiya S, Varella-Garcia M, West J, et al. Molecular definition of a small amplification domain within 3q26 in tumors of cervix, ovary, and lung. Cancer Genet Cytogenet 2000; l17:9-18.

24. Andersson S, Wallin KL, Hellström AC, Morrison LE, Hjerpe A, Auer G, et al. Frequent oin of the human telomerase gene,I1ERC at 3q26 in cervical adenocareinomas. Br J Cancer 2006; 95:33l-338.

25. Nakano K, Watney E, McDougall JK. Telomerose activity and expression of telomerase RNA component and telomerase catalytic subunit genein cervical cancer. Am J Pathol 1998; 153:857-864.

26. Allen DG, White DJ, Hutchins AM, Scurry JP, Tabrizi SN, Garland SM, et al. Progressive genetic abetrations detected by comparative genomic hybridization in squamous cell cervical cancer. Br J Cancer 2000; 83:1659-1663.

27. Caraway NP, Khanna A, Dawlett M, Guo M, Guo N, Lin E, Katz RL. Gain of the 3q26 region in cervicovaginal liquid-based pap preparations is associated with squamous intraepithelial lesions and squamous cell carcinoma. Gynecol Oncol 2008; 110:37-42.

28. Kokalj-Vokac N, Kodric T, Erjavec-Skerget A, Zagorac A, Takac I. Screening of TERC gene amplification as an additional genetic diagnostic test in detection of cervical preneoplastic lesions. Cancer Genet Cytogenet 2009; 195:19-22.

29. Alameda F, Espinet B, Corzo C, Muñoz R, Bellosillo B, Lloveras B, et al. 3q26 (hTERC) gain studied by fluorescence in situ hybridization as a persistence-progression indicator in low-grade squamous intraepithelial lesion cases. Hum Pathol 2009; 40:1474-1478.

30. Sui W, Ou M, Dai Y, Chen J, Lan H, Yan Q, et al. Gain of the human telomerase RNA gene TERC at 3q26 is strongly associated with cervical intraepithelial neoplasia and carcinoma. Int J Gynecol Cancer 2009; 9:1303-1306.

Bin H et al Screening Mark of Cervical Cancer

802

 

Iran J Basic Med Sci, Vol. 16, No. 6, Jun 2013

 

31. Yang YC, Shyong WY, Chang MS, Chen YJ, Lin CH, Huang ZD, et al. Frequent gain of copy number on the long arm of Chromosome 3 in human cervical adenocarcinoma. Cancer Genet Cytogenet 2001; 131:48-53.

32. Hildesheim A, Hadjimichael O, Schwartz PE, Wheeler CM, Barnes W, Lowell DM, et al. Risk factors for Rapid-onset cervical cancer. Am J Obstet Gynecol 1999; 180:57l-577.

33. McMurry HR, Nguyen D, Westbrook TF, McAnce DJ. Biology of human papillomaviruses. Int J Exp Pathol 2001; 2:15-33.

34. Hagensee ME, Koutsky LA, Lee SK, Grubert T, Kuypers J, Kiviat NB, et al. Detection of cervical antibodies to human papillomavirus type 16(HPV-16) capsid antigens in relation to detecion of HPV-16 DNA and cervical lesions. J Infect Dis 2000; 81:1234-1239.

35. Heselmeyer-Haddad K, Janz V, Castle PE, Chaudhri N, White N, Wilber K, et al. Detection of genomic amplification of the human telomerase gene (TERC) in cytologic specimens as a genetic test for the diagnosis of cervical dysplasia. Am J Pathol 2003; 63:1405-1416