NIK- and IKK2-Binding Protein: A Novel Marker of Breast Cancer
Shobha Parajuli, Hong Wang, Wenhui Hu, Xinmin Zhang. Temple University Hospital, Philadelphia, PA; Temple University School of Medicine, Philadelphia, PA
Background: Nuclear factor of κB (NF-κB) has been shown to modulate expression of genes involved in cell proliferation, differentiation, apoptosis and metastasis. The IκB kinase-2 (IKK2) and NF-κB–inducing kinase (NIK) are proteins involved in classical and alternative pathways of NF-κB activation. NIK- and IKK2- binding protein (NIBP) is a novel protein which bridges these two pathways and enhances cytokine-induced NF-kB activation in various cancer cell lines. Upregulation of NIBP mRNA expression in breast cancer cell lines and tumor tissues has been identified through bioinformatics. This study is undertaken to evaluate the NIBP protein expression in benign breast tissue and in breast cancer and to explore the clinical correlation of its expression with tumor grades and stages.
Design: Immunohistochemistry for NIBP was performed on a high density breast cancer tissue array (616 cores from 322 cases). Cytoplasmic staining of glandular epithelial or cancer cells in each core was assessed by two pathologists blind to the clinical information and it was scored semi-quantitatively as negative (0), weekly positive (1+), moderately positive (2+) or strongly positive (3+). Mann-Whitney two-tailed U test was employed for the statistical analysis using GraphPad Prism software.
Results: Materials from 26 benign breast tissue and 258 carcinomas were available for the study, including 242 invasive ductal carcinomas, not otherwise specified (IDC-NOS), 4 invasive lobular carcinomas, 6 mucinous carcinomas, 3 medullary carcinomas, 2 tubular carcinomas and 1 ductal carcinoma in situ. Among the invasive carcinomas, staging was available in 257 cases (24 Stage I, 198 Stage II and 35 Stage III) and grading in 237 cases (13 Grade I, 178 Grade II and 46 Grade III). NIBP expression was found significantly upregulated in carcinomas, in comparison to benign breast epithelium (p<0.001). Its expression was correlated partially with the tumor staging: higher level of protein expression was noted in Stage III carcinomas than that in Stage I carcinomas (p<0.05), although correlation with tumor grading was not significantly established in this cohort of invasive carcinomas. Its expression was significantly higher (p<0.05) in IDC-NOS than that of the special types of invasive carcinomas that have relatively better prognosis.
Conclusions: The results suggest that NIBP is a novel tumor marker of breast cancer and its expression may be associated with patient's prognosis. Further study to validate these findings is required in a larger scale of routine tissue samples.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 34, Monday Morning