Scientific publications

p16INK4a expression and breast cancer risk in women with atypical hyperplasia

Radisky DC, Santisteban M, Berman HK, Gauthier ML, Frost MH, Reynolds CA, Vierkant RA, Pankratz VS, Visscher DW, Tlsty TD, Hartmann LC.
Biochemistry and Molecular Biology, Mayo Clinic Cancer Center

Magazine: Cancer Prevention Research

Date: Sep 15, 2011

Breast Cancer Area Medical Oncology


p16, a nuclear protein encoded by the p16INK4a 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 Ki67 and COX2.

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 percent of cells positive and intensity of staining. We also studied coexpression of p16, with Ki67 and COX2, 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). While risk of developing breast cancer was not associated with increased p16 expression, joint overexpression of Ki67 and COX2 was found to convey stronger risk of BC in the first 10 years after diagnosis as compared to 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 COX2 and Ki67, does not significantly stratify breast cancer risk in women with AH.

CITATION  Cancer Prev Res (Phila). 2011 Sep 15

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