Morphometric analysis of DNA ploidy and nuclear cell cycle regulators in Ewing's sarcoma/primitive neuroectodermal tumor.

Abstract

Objective: To study the morphometry of DNA ploidy as a prognostic factor, compare qualitative and quantitative methods using immunohistochemical markers, and evaluate the utility of morphometry in the differential diagnosis of Ewing's sarcoma family of tumor (ESFT) subtypes and small round cell tumors (SRCTs) of bone.

Study design: A total of 111 genetically confirmed ESFTs and 19 SRCTs were evaluated for DNA content and immunohistochemistry for p53, p16, and Ki-67 using morphometric analysis. Qualitative evaluation was performed using light microscopy.

Results: Of the ESFT cases, 81% were aneuploid. Overall, no statistical differences were observed regarding the nuclear area or roundness between ESFT and SRCT and between ESFT subtypes. p53 and p16 revealed high concordance between qualitative and quantitative methods and a lower agreement using Ki-67. Nuclear roundness showed prognostic significance in the univariate analysis for proportional risk survival but no independent prognostically significant variable was obtained after multivariate analysis.

Conclusion: DNA content, nuclear area, or roundness cannot distinguish between ESFT and other SRCT. Morphometric analysis cannot discriminate between ESFT histologic subtypes. Quantitative measurements of IHC parameters are more precise than conventional measurements, particularly in discrepant cases (--vs. +, ++ vs. +++). DNA ploidy is not a prognostic factor in ESFT.