Stage-specific frequency and prognostic significance of aneuploidy in patients with sporadic colorectal cancer--a meta-analysis and current overview

Abstract

Purpose: Aneuploidy has long been suggested as an independent prognostic marker for colorectal cancer (CRC) patients and could thus aid for individualized medicine. However, due to a large spectrum of deviating studies, expert panels do not recommend ploidy assessment. In order to clarify a potential bias of stage-specific frequency of aneuploidy, we now conducted a meta-analysis combined with a systematic review regarding aneuploidy and prognosis.

Methods: A systematic, web-based search process retrieved 1935 studies published in English between 1990 and 2011. The defined endpoint for the meta-analysis was an increase in aneuploidy frequency between early- (Dukes A, B and UICC I, II; n = 3632 samples) and late-stage (Dukes C, D and UICC III, IV; n = 3440 samples) colorectal carcinomas.

Results: Of 1935 studies initially identified, 17 image (2130 patients) and 20 (7023 patients) flow cytometric studies were analyzed in detail. The meta-analysis (7072 patients) revealed late-stage CRC to be more frequently aneuploid than early-stage CRC (odds ratio 1.51, 95 % CI 1.37-1.67; p = 0.0007). Independent of tumor stage, the overall range of aneuploidy was 39 to 81 % (median 58 %), and altogether, 21 (54.1 %) studies described a significant prognostic impact of aneuploidy for overall, disease-specific, and recurrence-free survival, respectively.

Conclusions: A substantial number of studies showed a prognostic importance of aneuploidy in CRC. Furthermore, the higher frequency of aneuploidy in late-stage CRC implies an increase in genomic instability with CRC progression, indicating aneuploidy to be also a stage-specific prognostic marker.