Abstract
Abstract
Phosphatase and tensin homolog (PTEN) detected on chromosome 10 is a tumour suppressor commonly reported to be inactivated in colorectal cancers, but the prognostic significance of PTEN remains controversial. Here, we investigated the clinical associations and the significant prognostic value of combined PTEN mutation, genomic deletion and loss of expression in a large cohort of Middle Eastern colorectal cancers. We examined PTEN protein expression using immunohistochemistry in 400 sporadic colorectal cancers with full clinical investigations and follow up data. PTEN mutations were studied using capture sequencing and Sanger sequencing validation. PTEN copy number alteration was carried out using Fluorescence In-Situ Hybridization (FISH). Of the all CRC tumours analysed 83/347 (24%) cases showed absence of PTEN staining, 189/347 (54.5%%) cases showed weak staining and remaining 75/347 (21.5%) cases showed staining similar to normal & internal positive control. 17 mutations in coding region of PTEN were identified in 13 (3.2%) CRC cases. Further, PTEN deletion was identified in 24/338 (7.1%) of CRC cases. No amplification of PTEN gene was detected. Interestingly when combining all PTEN alterations (protein expression loss, PTEN mutation and PTEN genomic deletion), it accounted for 97 (29.7%) CRC cases. Significant association of combined PTEN alterations was seen disease free survival (p = 0.0367). On multivariate analysis, this stands true (p = 0.0227) when adjusted for Age, Sex, Site, Grade and Stage. Thus, PTEN alteration is an independent marker of poor prognosis in CRC. In conclusion, PTEN gene alteration plays an important role in Middle Eastern colorectal cancer pathogenesis and it can help in identifying a subgroup of CRC with particular poor outcome.
Citation Format: Abdul K. Siraj, Shaham Beg, Rong Bu, Maha Al-Rasheed, Nasser Al-Sanea, Fouad Al-Dayel, Khawla Al-Kuraya. Prognostic significance of PTEN alteration in Middle Eastern colorectal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3676.