Expression of Biologic Markers and DNA Ploidy Analysis in Atypical Ductal Hyperplasia and Ductal Carcinoma in Situ of the Breast

Kim, Hee Jung; Jung, Woo Hee; Jeong, Hyeon Joo; Lee, Hy De

Abstract

Status of margins and the size of the lesion are independent prognostic factors of ductal carcinoma in situ (DCIS). Histologic grading of DCIS and expression of biologic marker also appear to act as prognostic factors. However, DNA ploidy analysis using flow cytometry in the DCIS and atypical ductal hyperplasia (ADH) has been rarely reported, and the biologic behavior of ADH is unknown. We performed immunohistochemical staining and DNA ploidy analysis using flow cytometry on 45 cases of pure DCIS without microinvasion and 34 cases of ADH to compare the expression of biologic markers and DNA ploidy patterns according to the histologic grade of DCIS, to evaluate the usefulness of the Van Nuys classification, and to investigate the biologic behavior of ADH and low grade DCIS. A total of 41.9% of DCIS and 32.1% of ADH were detected mammographically in asymptomatic patients. The most common subtype of the high grade DCIS was comedo type (56.3%), while the low and intermediate grade DCIS were cribriform type. Expression of ER, c-erbB-2 and Ki-67 proliferative index (PI) was significantly associated with nuclear grade and histologic grade of DCIS. Expression of c-erbB-2 was also significantly correlated with presence of necrosis. In low grade DCIS, Ki-67 PI was significantly higher than ADH. A total of 63.6% of DCIS and 70% of ADH were diploidy and 15.9% of DCIS was aneuploidy. There was no aneuploidy in ADH. No significant association was noted between DNA ploidy and histologic grade or nuclear grade. However, in high grade DCIS, the frequency of aneuploidy was high. In conclusion, histologic grading of DCIS employing nuclear grade and necrosis is a useful tool accounting for biologic behavior. High grade DCIS and comedo DCIS impart aggressive biologic behavior and suggest a higher possibility of local recurrence or progression to invasive carcinoma. In the differential diagnosis of ADH and low grade DCIS, the use of Ki-67 PI and DNA ploidy analysis by flow cytometry will be helpful for accurate diagnosis and prediction of biologic behavior.