Overexpression of p16 Does Not Indicate Increased Risk of Breast Cancer in Women with Atypical Hyperplasia

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Women diagnosed with atypical hyperplasia have a substantial risk of subsequent development of breast cancer, with a cumulative incidence of approximately 30% at 25 years. Atypical hyperplasia is considered to be a precursor to ductal carcinoma in situ (DCIS). p16 (a nuclear protein encoded by the p16INK4a gene) plays an important role in cell-cycle regulation, and a number of studies have shown that expression of p16 in biopsies of patients with DCIS is associated with increased risk of breast cancer, particularly when considered in combination with other markers such as Ki-67 (proliferation marker) and COX-2 (inflammatory/invasive marker).

In a recent study, Radisky and colleagues from the Mayo Clinic Department of Cancer Biology in Jacksonville, Florida, found no association of increased p16 expression and risk for development of breast cancer in women with atypical hyperplasia.1 The investigators assessed expression of p16, Ki-67, and COX-2 in archived sections from 233 women with atypical hyperplasia diagnosed at the Mayo Clinic. With a median follow-up of 14.5 years, 47 patients (20%) developed breast cancer. Expression of p16 was significantly increased in older patients compared with younger patients. Joint overexpression of Ki-67 and COX-2 was found to convey significantly greater risk of breast cancer in the first 10 years after diagnosis, compared with overexpression of only one of these markers. However, the addition of p16 expression levels to the analysis did not strengthen the association of Ki-67 and COX-2 with cancer risk.

As stated by the authors, “p16 overexpression, either alone or in combination with COX-2 and Ki-67, does not significantly stratify breast cancer risk in women with [atypical hyperplasia].” The finding of an increased proportion of p16-positive lesions in older women is consistent with other studies showing age-related increases of p16 in other tissues. The authors noted that “Determining whether the increased abundance of p16-positive cells in [atypical hyperplasia] of older women is associated with tumor protective or promoting effects of senescence activation will require further investigation.” ■

Radisky DC, et al: Cancer Prev Res 4:1953-1960, 2011.




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