Further to advancements in instrumentation and fluorescent dye technologies, there has been a resurgence of interest in the flow cytometric assay of formalin-fixed, paraffin-embedded specimens. Here we present a novel, simple and effective alternative to whole block sectioning that allows selective multisampling of tissues within a specimen block and the investigation of intratumoral heterogeneity. Formalin-fixed, paraffin-embedded breast carcinoma specimens were core-punched using 1.0 mm diameter needles and assayed by flow cytometry using a modified Hedley method. Intratumoral heterogeneity for DNA index and per cent S-phase fraction was detected in 10 of 23 (44%) and 11 of 23 (47%) specimens respectively. Macro-level genomic heterogeneity is common in breast cancer even within a single surgical specimen block. Studies investigating the relationship of DNA content heterogeneity to other markers of genomic instability such as mutations, deletions, insertions and translocations are warranted.
