Analysis of Anaphase Figures in Routine Histologic Sections Distinguishes Chromosomally Unstable from Chromosomally Stable Malignancies

Abstract

A classification of neoplasms as chromosomally stable vs. unstable is of importance in assessing inherited risks but is primarily defined in cell lines where rates of instability can be directly measured. The confirmation of such a mechanistic theory in primary tissues is desirable. We examined anaphase figures in histologic slides to evaluate such criteria. The process of chromosomal instability (CIN) involves mis-segregation of chromosomes at anaphase in some or most instances, whereas chromosomally stable tumors should lack these particular abnormalities.1 Anaphase bridges are associated with chromosome mis-segregation and have occasionally been observed in colorectal neoplasia and in sarcomas, but have not been considered for use as a diagnostic tool.2 We assembled series of sarcomas, colorectal and pancreatic carcinomas belonging to two groups: those associated with or lacking chromosomal instability. Among the chromosomally stable tumors, all lacked anaphase bridges, while anaphase bridges were found in most sarcomas and carcinomas having complex genomic alterations. These results confirm a mechanistic explanation involving chromosome mis-segregation for primary human cancers having aneuploidy/CIN. A basic mechanistic distinction between neoplasms with CIN and those with minimal chromosomal changes is supported. Most importantly, our data suggest a diagnostic utility for the examination of anaphase bridges in the routine practice of pathology with a high potential to impact clinical decision-making processes regarding colorectal cancer treatment.