p16(INK4a) expression and breast cancer risk in women with atypical hyperplasia - PubMed (original) (raw)

p16(INK4a) expression and breast cancer risk in women with atypical hyperplasia

Derek C Radisky et al. Cancer Prev Res (Phila). 2011 Dec.

Abstract

p16, a nuclear protein encoded by the p16(INK4a) gene, is a regulator of cell-cycle regulation. Previous studies have shown that expression of p16 in tissue biopsies of patients with ductal carcinoma in situ (DCIS) is associated with increased risk of breast cancer, particularly when considered in combination with other markers such as Ki-67 and COX-2. Here, we evaluated how expression of p16 in breast tissue biopsies of women with atypical hyperplasia (AH), a putative precursor lesion to DCIS, is associated with subsequent development of cancer. p16 expression was assessed by immunohistochemistry in archival sections from 233 women with AH diagnosed at the Mayo Clinic. p16 expression in the atypical lesions was scored by percentage of positive cells and intensity of staining. We also studied coexpression of p16, with Ki-67 and COX-2, biomarkers of progression in AH. Risk factor and follow-up data were obtained via study questionnaire and medical records. Forty-seven patients (20%) developed breast cancer with a median follow-up of 14.5 years. Staining of p16 was increased in older patients relative to younger patients (P = 0.0025). Although risk of developing breast cancer was not associated with increased p16 expression, joint overexpression of Ki-67 and COX-2 was found to convey stronger risk of breast cancer in the first 10 years after diagnosis as compared with one negative marker (P < 0.01). However, the addition of p16 levels did not strengthen this association. p16 overexpression, either alone or in combination with COX-2 and Ki-67, does not significantly stratify breast cancer risk in women with AH.

2011 AACR

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Figures

Figure 1

Figure 1

Staining levels of p16 in AH. Samples of atypical ductal hyperplasia (ADH, left column) and atypical lobular hyperplasia (ALH, right column), showing fractional staining levels of <1% cells staining positively for p16 (top row), 1–10% p16+ cells (second row), 11–50% p16+ cells (third row), 51–90% p16+ cells (fourth row), and >90% p16+ cells (bottom row).

Figure 2

Figure 2

Expression of p16 is not related to cumulative breast cancer incidence or time to breast cancer for women with AH. Observed and expected events are cumulated after accounting for death as a competing risk and are plotted as a function of follow-up interval and stratified by p16 expression levels. Red line, 0–10% cells staining for p16; blue line, 11+% cells staining for p16; black line, expected breast cancer incidence according to Iowa Surveillance, Epidemiology, and End Results survey.

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