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Chapter 11

FIG. 11.56.  DCIS, HER2. A: HER2 membrane immunoreactivity is present in the DCIS extending into a lobule but not in nonneoplastic epithelial cells. B: HER2-positive, solid high-grade DCIS. C: HER2-positive micropapillary DCIS with high-grade nuclei and necrosis. D: HER2-negative inva- sive well-differentiated carcinoma ( right ) and HER2-positive solid DCIS ( left ).

actual measurements of nuclear size, Bartkova et al. 187 ob- served that 94% of DCIS composed of cells with large nuclei (20 μm) were positive for HER2, whereas no membrane re- activity was seen in cells with small nuclei (10 μm). Immu- noreactivity was present in 71% of DCIS with intermediate nuclear size (15 μm) and in 91% of lesions composed of cells with mixed nuclear size. In this series, a small number of papillary and clinging DCIS with large nuclei were immu- noreactive for HER2. Others have confirmed the finding of HER2 immunoreactivity in 85% of micropapillary or cling- ing DCIS with large or pleomorphic nuclei. 196 The neoplastic Paget cells in the eponymous disease of the nipple, as well as those of the associated underlying mammary DCIS, are ER negative and HER2 positive in more than 80% of cases. 197 HER2 immunoreactivity is found more often in DCIS with aneuploid nuclei than in carcinomas with diploid nu- clei, an association that correlates well with the reported relationship of HER2 to nuclear size. 190,194 There is also a strong association between positive HER2 reactivity and a high proliferative rate represented by the thymidine and MIB1 labeling indices. 194,198

The extracellular domain of HER2 can be detected in the serum of patients with invasive breast carcinoma, and this finding has been associated with overexpression in the car- cinoma detected by IHC. 199 Serum analysis for HER2 may prove to be a useful method for identifying patients with microinvasive duct carcinoma. Esteva-Lorenzo et al. 200 de- scribed a patient with elevated serum extracellular domain of HER2 at the time a breast biopsy demonstrated comedo DCIS that was immunoreactive for HER2. Reexcision per- formed because carcinoma involved the initial excision mar- gin revealed a microinvasive focus. Thereafter, the serum level of HER2 decreased to normal. No elevation of serum extracellular domain HER2 was detected by these authors in specimens from 8 other patients with DCIS, including 3 with DCIS immunoreactive for HER2, or in 27 patients with be- nign biopsies. In women with clinically invasive carcinoma, serial HER2 serum levels during the course of chemotherapy did not correlate well with the clinical status of the patients. 201 Less than 10% of DCIS have been characterized as having the basal-like phenotype on the basis of IHC. These uncom- mon instances of HER2 (−) high-grade DCIS are not readily