The Expression Level of pThoc1 Is Associated with Her2 Status and Tumor Size in Breast Cancer
Yanping Li, Jun Yang, Jorge A Almenara, Hope T Richard, Joseph P Bergeron, David W Goodrich, Michael O Idowu. Virginia Commonwealth University Health System, Richmond, VA; Virginia Department of Health, Richmond, VA; Roswell Park Cancer Institute, Buffalo, NY
Background: Human pThoc1 is a nuclear matrix protein originally isolated for binding to pRb, the product of RB1 tumor suppressor gene. Thoc1 protein is an essential component of transcription-elongation (TREX) complex, is upregulated in multiple human cancers and cancer cell lines, and is required for survival of cancer cells but not normal cells. We have previously shown that Thoc1 is required for early stage tumorigenesis in cell culture models (Li et al., Cancer Research, 2007) as well as prostate cancer mouse models (in press). However, the role of Thoc1 in human breast cancer is largely unknown. The purpose of the study is to evaluate the association of pThoc1 expression with clinicopathologic features in breast cancer.
Design: Breast carcinoma lobectomy or mastectomy cases from 1992 to 2008 at VCUHS with at least 5 years follow up or local recurrence/distant metastasis were selected. Tissue microarrays were created with triplicate tumor cores from each case. Immunohistochemical staining was performed with a rabbit polyclonal antibody to pThoc1 (Aviva, USA). Cases were scored for nuclear staining intensity (0-3) and percentage (0-100%). Thoc1 score was calculated by Intensity x Percentage. A score of >200 was considered strong. Statistical significance was determined using Chi-squared test and Pearson correlation analysis.
Results: Of 319 cases, 244 cases were scorable. Strong pThoc1 expression was associated with small tumor size, Her2 negativity and low Ki67. No significant correlation with tumor grade, stage, metastasis, local recurrence, age, ER, or PR was observed.
Conclusions: The association of strong pThoc1 expression with small tumor size, Her2 negativity and low Ki67 is consistent with our observation that pThoc1 is required for early tumorigenesis in cell culture and mouse models. Its unique mechanism in gene expression and tumorigenesis and differential requirement by tumor cells versus normal cells suggest that Thoc1 may be a good molecular target for cancer prevention or therapy.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 19, Wednesday Afternoon