PIWI-Like 1 and PIWI-Like 2 Expression in Breast Cancer

SIMPLE SUMMARY: A family of proteins, the PIWI proteins, play a crucial role in the regulation of the development of germ cells and self-preservation of so-called stem cells. Former studies have shown that these proteins can be over- or underrepresented (over-/underexpressed) in some cancers and, in the case of abnormal expression, may be correlated with worse outcomes of tumor patients. In our study, we investigated the influence of the two PIWI proteins, PIWI-like 1 and PIWI-like 2, on the survival of breast cancer patients and their correlation with certain breast cancer subtypes. If a breast cancer showed a higher expression of PIWI-like 1 protein but less PIWI-like 2 protein than in non-tumorous tissue, the patient suffered from a more aggressive breast cancer subtype and had shorter survival. By analyzing these two proteins in breast cancer, we were able to predict tumor aggressiveness and prognosis. ABSTRACT: PIWI-like 1 and PIWI-like 2 play a role in stem cell self-renewal, and enhanced expression has been reported for several tumor entities. However, few studies have investigated PIWI-like 1 and PIWI-like 2 expressions in breast cancer subtypes regarding prognosis. Therefore, we examined protein expression in a large consecutive cohort of breast cancer patients and correlated it to breast cancer subtypes and survival outcome. PIWI-like 1 and PIWI-like 2 expressions were evaluated using immunohistochemistry in a cohort of 894 breast cancer patients, of whom 363 were eligible for further analysis. Percentage and intensity of stained tumor cells were analyzed and an immunoreactive score (IRS) was calculated. The interaction of PIWI-like 1 and PIWI-like 2 showed a prognostic effect on survival. For the combination of high PIWI-like 1 and low PIWI-like 2 expressions, adjusted hazard ratios (HRs) were significantly higher with regard to overall survival (OS) (HR 2.92; 95% confidence interval (CI) 1.24, 6.90), disease-free survival (DFS) (HR 3.27; 95% CI 1.48, 7.20), and distant disease-free survival (DDFS) (HR 7.64; 95% CI 2.35, 24.82). Both proteins were significantly associated with molecular-like and PAM50 subgroups. Combining high PIWI-like 1 and low PIWI-like 2 expressions predicted poorer prognosis and both markers were associated with aggressive molecular subtypes.