Piwil2-Like (PL2L) Proteins Are a Potential Biomarker for Breast Cancer Progression
RL Shen, G He, C Shapiro, JJ Li, L Chen, Y Ye, SH Barsky, JX Gao. Ohio State University, Columbus, OH; Ohio State University Medical Center, Columbus, OH; UC Davis Cancer Center, Sacramento, CA
Background: The significance of piwil2 as tumor biomarker has been controversial. Recently, we have generated two monoclonal antibodies (mAbs) Kao1 and Kao2, which recognize piwil2 (Kao1) and piwil2/PL2L proteins (Kao2), respectively. We hypothesize that PL2L proteins rather than piwil2 are expressed in various developmental stages of tumor such as breast cancers.
Design: 400 breast tumor specimens including benign proliferation [ductal hyperplasia (DH) and metaplasia (DM), n=9], precancer [atypical ductal hyperplasia (ADH, n=5), and ductal carcinoma in situ/ductal cancerization (DCIS, n=6), and malignant cancer [invasive ductal carcinoma (IDC) and metastatic cancers (Met-ca), n=379] were prepared as tissue microarrays (TMAs) and were immunohistochemically analyzed for piwil2 and PL2L proteins expression. Because piwil2 and NF-kB are implicated for tumor stem cell (TSC) development, some TMAs were doubly stained with mAb Kao2 and NF-kB.
Results: Among 400 breast cancer specimens, only was <1% of the TMA cores stained within an apoptotic focus by Kao1 mAb, whereas >95% of the TMA cores was stained by Kao2 mAb with individual variations, suggesting that PL2L proteins rather than piwil2 were dominantly expressed in breast cancers. While almost all Kao2+ cells were co-stained in cytoplasm by mAb to NF-kB, not all NF-kB+ cells were co-stained by Kao2 mAb. Interestingly, some Kao2+NF-kB+ cells were also stained in nucleus (< 1% to 35% of Kao2+NF-kB+ cells). The nuclear Kao2+NF-kB+ cells appeared to be associated with tumor progression, because these cells were rarely detected in the benign proliferation lesions (DH and DM) and precancerous lesions (ADH) except for DCIS, about 50% of which was detected with nuclear Kao2+NF-kB+ cells, especially in the ductal cancerization areas. These results suggest strongly that nuclear Kao2+NF-kB+ cells might signify histological and clinical progression of breast cancers.
Conclusions: PL2L proteins rather than piwil2 are dominantly expressed in breast cancers, which have the potential to be used as a breast cancer biomarker for early detection. The nuclear Kao2+FN-kB+ cells might be significant for prediction of breast tumor progression and prognosis.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 12, Wednesday Afternoon