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Chapter 11

Numerical alterations in individual chromosomes have been studied by fluorescence in situ hybridization (FISH) us- ing specific probes. Using this method in paraffin sections of archival tissue samples, Visscher et al. 222 detected chromo- somal aneuploidy in 7 to 10 specimens of DCIS. Aneuploidy was more frequent in specimens from patients with concur- rent invasive carcinoma. Patterns of aneuploidy consisted of gains only, losses only, or gains and losses involving different chromosomes. Aneuploidy was most frequent for chromo- somes 16 and 17. HER2-positive and triple-negative types of DCIS, to a greater degree than the “luminal” types of DCIS, show DNA aneuploidy, as assessed by image analysis. 223 The proliferative activity in DCIS is now usually analyzed by IHC (Fig. 11.59). Albonico et al. 195 reported the highest PI in lesions of the comedo type. Other types of DCIS had much lower PIs: solid 14.4%, papillary 13.4%, cribriform 4.5%, and micropapillary 0%. DCIS can be graded using

Ploidy and Proliferative Rate When studied by flow cytometry, the frequency of aneuploidy in DCIS ranges from 21% to 71%. 215–220 The clinical relevance, and need, for this information has diminished over the years. Aneuploidy has been found in 55% tomore than 90% of come- docarcinomas 215,216,218,219 and in 65%of DCIS with high nuclear grade. 217 Image analysis of Feulgen-stained tissue sections re- vealed aneuploidy in 77.5% of DCIS, predominantly in lesions with high (100%) and intermediate (80%) nuclear grade. 207 Thymidine labeling and flow cytometry studies demon- strated a significantly higher proliferative rate in comedo- carcinoma than in cribriform–micropapillary DCIS. 189,221 All papillary DCIS examined in one series were diploid. 219 Cribriform DCIS tend to be diploid with a low S-phase frac- tion (SPF). 218,220 Sataloff et al. 220 reported that micropapillary DCIS was typically diploid with a low SPF.

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FIG. 11.59.  DCIS, Ki67 proliferation marker. A: Nuclear immunoreactivity for Ki67 is present in very few neoplastic cells in the basal region of cribriform DCIS with low-grade nuclei. B: Ki67 reactiv- ity observed in less than 10% of cells in this micropapillary DCIS with intermediate-grade nuclei. Nuclear reactivity is mostly localized to the basal region in this example also. C: Approximately 10% of the neoplastic cells are Ki67 reactive in this solid DCIS. D: Approximately one-third of the neoplastic cells are reactive for Ki67 in this solid high-grade DCIS with necrosis ( left ).