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Gynecol Oncol. 2013 Mar;128(3):420-6. doi: 10.1016/j.ygyno.2012.11.041. Epub 2012 Dec 7.

Downregulation of tumor suppressor gene PML in uterine cervical carcinogenesis: impact of human papillomavirus infection (HPV).

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  • 1Department of Biotechnology, Panjab University, Chandigarh, India.

Abstract

OBJECTIVES:

Cervical cancer is a leading gynecological cancer in Indian women and is caused due to infection with high risk human pappilloma virus (HR-HPV) 16 and 18. It has been well documented that PML (promyelocytic leukemia) enhances viral infectivity and plays a crucial role in antiviral response mechanisms. The aim of the present study was to evaluate the role of PML gene with context to HPV infection in cervical carcinogenesis.

METHODS:

The expression pattern of PML was analyzed by western blotting and immunohistochemistry in a total of 170 fresh surgically resected cervical tissue specimens comprising precancer (n=12), cancer (n=118) and normal controls (n=40) recruited from PGIMER, Chandigarh, India. HPV status was analyzed by L1 consensus PCR followed by type specific PCR for HR-HPV types 16 and 18 and low risk types 6 and 11.

RESULTS:

A significant downregulation of PML protein was observed in the majority of cervical cancer and precancer cases 68% (89/130) compared to normal controls. The loss of expression pattern of PML gene was significantly increased with severity of disease both clinically and pathologically (p<0.001). HPV infection was detected in the majority of cancer cases 96% (113/118) and in 83% (10/12) of precancer lesions whereas no infection could be detected in normal controls. Interestingly, all the 68% (89/130) cervical cancer cases that showed downregulation of PML were HPV infected (p=0.0001).

CONCLUSION:

Taken together, these observations suggest that the downregulation of PML gene and its synergism with HPV infection may play an important role and may serve as a new marker for early diagnosis and therapeutic intervention for cervical carcinogenesis.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
23220564
[PubMed - indexed for MEDLINE]
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