p53 nuclear accumulation and ERalpha expression in ductal hyperplasia of breast in a cohort of 215 Chinese women

Abstract

Introduction: Women with ductal hyperplasia including usual ductal hyperplasia (UDH) and atypical ductal hyperplasia (ADH) have an increased risk of developing invasive ductal carcinoma (IDC) of breast. The importance of several molecular markers in breast cancer has been of considerable interest during recent years such as p53 and estrogen receptor alpha (ERalpha). However, p53 nuclear accumulation and ERalpha expression have not been assessed in ductal hyperplasia co-existing with ductal carcinoma in situ (DCIS) or IDC versus pure ductal hyperplasia without DCIS or IDC.

Materials and methods: We investigated p53 nuclear accumulation and ERalpha expression in breast ductal hyperplasia in a cohort of 215 Chinese women by immunohistochemistry (IHC), which included 129 cases of pure ductal hyperplasia, 86 cases of ductal hyperplasia co-existing with DCIS (41 cases) or IDC (45 cases).

Results: Nuclear p53 accumulation was identified in 22.8% of ADH (31/136), 41.5% of DCIS (17/41) and 42.2% of IDC (19/45), and no case of UDH (0/79). No difference in nuclear p53 accumulation was observed between pure ADH and ADH co-existing with DCIS (ADH/DCIS) or IDC (ADH/IDC) (P>0.05). The positive rate of ERalpha expression was lower in ADH (118/136, 86.8%) than that in UDH (79/79, 100%) (P<0.001), but higher than that in DCIS (28/41, 68.3%) or IDC (26/45, 57.8%) respectively (P<0.001). The frequency of ERalpha expression was lower in ADH/DCIS (23/29, 79.31%) and ADH/IDC (23/30, 76.67%) than that in pure ADH (72/77, 93.51%) respectively (P<0.05). There was a negative weak correlation between p53 nuclear accumulation and ERalpha expression as for ADH (coefficient correlation -0.51; P<0.001).

Conclusions: Different pathological types of ductal hyperplasia of breast are accompanied by diversity in patterns of nuclear p53 accumulation and ERalpha expression. At least some pure ADH is molecularly distinct from ADH/CIS or ADH/IDC which indicated the two types of ADH are molecularly distinct entities although they have the same morphological appearance.

Figure 1

Immunohistochemical staining of noninvasive breast lesions with antibody against p53. p53 nuclear accumulation was not found in epithelial cells of normal ducts (a) and usual ductal hyperplasia (b) of breast. p53 positive staining in atypical ductal hyperplasia (c): the bigger arrow shows a breast duct filled with cells with atypical hyperplasia. The cells are quite identical in size and shape. Staining of p53 is seen in some nuclears (> 10%). The little arrow shows a normal duct without p53 nuclear accumulation. p53 positive staining in ductal carcinoma in situ (d): the bigger arrow shows a ductal carcinoma in situ with positive staining of p53 in nuclears (> 10%). The little arrow shows necrosis in the ductal carcinoma in situ. (× 40)

Figure 2

ERα expression in noninvasive breast lesions. a: ERα staining in epithelial cells of normal ducts (smaller arrow) and usual ductal hyperplasia (bigger arrow) of breast was located in nuclear. b: ERα staining was seen in all epithelial cells of a normal duct (smaller arrow) but was reduced in cells in a co-existing duct with atypical ductal hyperplasia (bigger arrow). c: The arrow shows a breast duct with atypical ductal hyperplasia with positive staining of ERα (> 10%) which was absent in some cells. d: ERα staining in a ductal carcinoma in situ was negative (< 10%). The arrow shows the necrosis. (× 40)

Figure 3

A case of ADH of breast with concurrent increased p53 nuclear accumulation (a) and reduced ERα expression. There were some cells (> 10%) with weak p53 staining in a. While some cells (> 10%) were absent of ERα staining in b.