Aberrant promoter methylation and inactivation of PTEN gene in cervical carcinoma from Indian population
- 383 Downloads
PTEN, a tumor-suppressor gene located on chromosome 10q23.3 is implicated in multiple tumors including cervical carcinoma.
We examined 135 cervical cancer specimens for PTEN gene expression and promoter methylation using methylation-specific PCR and immunohistochemistry and also studied the mutation in PTEN gene through PCR-single-stranded conformational polymorphism. PTEN expression and its methylation status were also correlated with clinicopathologic parameters.
The results showed an abnormal band on exon 5 and exon 9 of the PTEN gene. In PTEN gene, 61% specimen showed methylation. PTEN methylation was found in 39% cases of stage I, 60% of stage II, and 75% of stages III–IV. The correlation between PTEN methylation and clinical stage was found to be statistically significant (P = 0.003). Nuclear PTEN expression was detected in 84 of 135 (62%) cases of cervical carcinoma, and the remaining 51 of 135 (38%) cases were observed as expressional loss. The loss of PTEN expression was significantly correlated clinical stage (P = 0.001). Loss of PTEN expression was observed in 34 (41%) cases among 83 methylation positive cases, whereas among 52 methylation-negative cases, only 13 (25%) cases were seen as immunostaining negative with the statistically significant value (P = 0.05).
Promoter methylation and loss of PTEN expression occur frequently in carcinoma of uterine cervix. Our results suggest that PTEN plays an important role in the carcinogenesis of cervical cancer.
KeywordsPTEN Cervical cancer Methylation Immunohistochemistry
The authors acknowledge University Grants Commission (UGC), Government of India, New Delhi, for providing the fund for this study. The authors also acknowledge Mr. M. Irshad and Mr. Irfan Ahmad for their valuable suggestions during the manuscript preparations.
Conflict of interest
- Alam MS, Rizvi MM (2011) Cancer of the uterine cervix and PTEN tumor suppressor gene. Lambert Academic Publishing, GermanyGoogle Scholar
- American Cancer Society (2009) Cancer facts & figures. American Cancer Society, AtlantaGoogle Scholar
- Ferlay J, Bray F, Pisani P, Parkin DM (2004) GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. In: IARC Cancer base No. 5, version 2.0. IARC Press, LyonGoogle Scholar
- National Cancer Registry Programme (2007) Consolidated report of hospital based cancer registries 2001–2003. ICMR, New DelhiGoogle Scholar
- Preacher KJ (2001) Calculation for the chi-square test: an interactive calculation tool for chi-square tests of goodness of fit and independence [Computer software]. Available from http://www.quantpsy.org
- Reid AHM, Attard G, Ambroisine L, Fisher G, Kovacs G, Brewer D, Clark J, Flohr P, Edwards S, Berney DM, Foster CS, Fletcher A, Gerald WL, Møller H, Reuter VE, Scardino PT, Cuzick J, de Bono JS, Cooper CS (2010) Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer. Br J Cancer 102:678–684PubMedCrossRefGoogle Scholar
- Sambrook J, Russell DW (2001) Molecular Cloning: A Laboratory Manual, 3rd edn. Cold Spring Harbor Lab. Press, plainviewGoogle Scholar