P16 Expression and Its Correlation with Ki67 in Triple-Negative Breast Carcinoma
Jessica Z Sugianto, Venetia Sarode, Sunati Sahoo, Yisheng Fang, Dwight Oliver, Yan Peng. University of Texas Southwestern Medical Center, Dallas, TX
Background: Triple-negative breast carcinoma (TNBC) characterized by negativity of ER, PR, and HER2 is associated with a poor prognosis due to its aggressive behavior and lack of conventional therapeutic targets. Many TN tumors resemble squamous cell carcinoma morphologically. Diffuse p16 expression is a surrogate marker for high risk HPV-related squamous cell carcinoma. High Ki67 expression is associated with worse prognosis in TN cancer patients. P16 expression in TNBC and its correlation with Ki67 expression have not been well characterized. We investigated p16 expression in TNBC cases to explore its potential prognostic value.
Design: Sixty high grade invasive TNBC cases were identified at our institution (2004 - 2011). Tissue microarrays (TMAs) were constructed with duplicate representative cores of each tumor and adjacent normal breast ducts. The TMAs were immunolabled for p16, Ki67 and p53. P16 stain was scored based on intensity and extent of nuclear and cytoplasmic staining as follows: negative (0), weak/1-30% (1), moderate/31-60% (2), moderate to strong/61-90% (3), strong/91-100% (4). Immunostained slides were reviewed and scored by two pathologists (YP, JS). A final average score of each case was used for statistical analysis. Ki67 and p53 stains were evaluated by image analysis. We compared p16 expression of tumors and adjacent normal tissue. Correlation analysis was performed between p16 and Ki67 or p53 expression.
Results: TN tumors were found to have significantly higher expression of p16 compared with adjacent normal breast ducts (2.075 ± 0.216 vs.0.146 ± 0.044, p<0.0001; paired T-test). 42% of the tumors demonstrated diffuse or near diffuse p16 expression (score of 3 or 4). All the tumors showed high Ki67 expression, but only 37 of 60 (62%) were p53-positive (>1%). Among p53-negative tumors (23, 38%), p16 expression (2.44 ± 0.309) positively correlated with Ki67 (65.22% ± 7.23; r=0.739, p<0.001; Pearson correlation). No correlation was found between p16 and Ki67 expression among the p53-positive tumors (r=0.157).
Conclusions: P16 expression is significantly increased in TN tumors compared with paired normal breast ducts. Its expression correlates with Ki67 in p53-negative but not p53-positive TN tumors, suggesting p16 may have a prognostic value in p53-negative TN tumors. Further study is needed to better define the role of p16 as a potential prognostic marker. Primary TNBC can resemble HPV-related sqaumous cell carcinoma not only morphologically but also immunophenotypically with strong diffuse p16 expression; this can be helpful in identifying metastatic TNBC.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 42, Monday Morning