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. 2009 Dec;2(4):264-70.
doi: 10.1593/tlo.09148.

Promoter Hypermethylation in Tumor Suppressing Genes p16 and FHIT and Their Relationship with Estrogen Receptor and Progesterone Receptor Status in Breast Cancer Patients from Northern India

Mohammad Raish  1 , Varinderpal S Dhillon, Arif Ahmad, Mushtaq Ahmad Ansari, Shahid Mudassar, Mohammad Shahid, Vineeta Batra, Pawan Gupta, Bhudev Chandra Das, Nk Shukla, Syed Akhtar Husain
Affiliations

Promoter Hypermethylation in Tumor Suppressing Genes p16 and FHIT and Their Relationship with Estrogen Receptor and Progesterone Receptor Status in Breast Cancer Patients from Northern India

Mohammad Raish et al. Transl Oncol. 2009 Dec.

Abstract

Background: Aberrant DNA methylation has been recognized in human breast carcinogenesis as a common molecular alteration associated with the loss of expression of a number of key regulatory genes. The present study was undertaken to determine whether methylation and expression of p16 and FHIT genes would correlate with the estrogen receptor (ER) and progesterone receptor (PR) status.

Methods: Methylation-specific polymerase chain reaction, messenger RNA (mRNA) expression analysis, immunohistochemistry, and Western blot analysis were performed to study the methylation of p16 and FHIT genes in 351 pairs of malignant/normal breast tissues. We examined the expression of ER and PR in those specimens by immunohistochemistry. Mutations of p16 and FHIT genes in tumors were detected by direct sequencing.

Results: The frequency of hypermethylation was 31.9% and 36.8% in p16 and FHIT genes, respectively, and showed significant harmony in concordant hypermethylation (P < .0001). In postmenopausal patients, methylation frequency in both genes is significantly higher in poorly and moderately differentiated tumors. Loss of protein expression of p16 and FHIT in 77 and 74 tumors, respectively, is associated with their methylation status in premenopausal women.

Conclusion: We did not find any significant differences in tumor-related gene methylation patterns relevant to both ER and PR status of breast tumors.

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Figures

Figure 1
Figure 1
(A) Methylation status of p16 and FHIT genes in normal and tumor tissues from the same patient. (B) Northern blot analysis showing mRNA expression profile of FHIT, p16, and β-actin in different breast cancer patients. Lane marked N: normal breast tissue, T: tumor tissue. (C) Western blot analysis in the same patients analyzed for Northern blot.
Figure 2
Figure 2
Immunohistochemical detection of p16 and FHIT protein in breast cancer patients. (A–C) Progressive loss of p16 in different patients: (A) normal epithelium shows consistent and strong staining for p16, (B) low or reduced p16 expression, and (C) no expression of p16. (D–E) Progressive loss of FHIT in different patients: (D) normal epithelium of breast tissue stains consistently and strongly for FHIT protein; (E) low or reduced expression of FHIT gene; and (F) no expression of FHIT protein in breast cancer patients.
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