Immunohistochemical expression and mutation study of Prohibitin gene in Indian female breast cancer cases

• Published in: Medical oncology (Northwood, London, England) London, England), 2013-09, Vol.30 (3), p.614, Article 614
• Main Authors: Najm, Mohammad Zeeshan, Zaidi, Shuaib, Siddiqui, Waseem Ahmad, Husain, Syed Akhtar
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Exons - genetics; Female; Genes, p53 - genetics; Hematology; Humans; Immunohistochemistry - methods; India; Internal Medicine; Introns - genetics; Medicine; Medicine & Public Health; Middle Aged; Mutation - genetics; Oncology; Original Paper; Pathology; Repressor Proteins - genetics
• ISSN: 1357-0560; 1559-131X
• DOI: 10.1007/s12032-013-0614-8

Prohibitin (PHB1) is highly conserved and ubiquitously expressed protein. It is mapped to the chromosome 17q12–q21 locus, a region that has been reported to be genetically linked to early onset of breast cancer. Therefore, we carried out the population-based study in a total of 105 Indian female breast cancer cases and analyzed mutation(s) on exon 4 and the introns flanking it. Importantly, it has been found that the region of this exon has specific binding site for Rb and p53 gene. We further did protein expression of Prohibitin through immunohistochemistry in the same set of population where mutation has already been found. Out of 105 breast cancer cases, 46 cases (46/105, 43.8 %) showed low or no expression (+), 19 cases (19/105, 18.0 %) with moderate (++) expression and 40 cases (40/105, 38.0 %) had high (+++) expression for Prohibitin . Highly significant association was observed statistically between Prohibitin protein expression and clinico-pathological variables like nodal status ( p  = 0.0003), tumor stage ( p  = 0.0001), histological grade ( p  = 0.009). Moreover, the previously found mutation(s) when analyzed with the immunohistochemistry data revealed that all the breast cancer cases with mutation representing intron deletion (deletion of T nucleotide) near the intron–exon boundary had low (+) or no expression for Prohibitin . In summary, Prohibitin may be associated with breast cancer and its down expression can serve as a potential biomarker for the effective assessment of the disease.