Intercorrelation of Cell Cycle Markers in Squamous Cell Carcinomas of the Penis
George J Netto, Antonio L Cubilla, Rajni Sharma, Jessica Hicks, Kristen L Lecksell, Alcides Chaux. Johns Hopkins University, Baltimore, MD; Instituto de Patologia e Investigacion, Asuncion, Paraguay
Background: Previous studies have suggested a link between tumor morphology and expression of specific cell cycle markers in penile squamous cell carcinomas (SCC). However, studies assessing the intercorrelation between molecular pathways involved in cell proliferation and apoptosis are scant. Herein, we evaluated the status and intercorrelation of 5 cell cycle and apoptosis related markers in a large series of penile carcinomas.
Design: One-hundred and twelve penile SCC were used to build 4 tissue microarrays. TMA spots were scanned using the APERIO system and uploaded to the TMAJ platform (http://tmaj.pathology.jhmi.edu). The following cell cycle and apoptosis related markers were evaluated by immunohistochemistry: p16INK4a, p53, MDM2, Cyclin-D1, and Ki-67. For each marker, extent (percent of positive cells) was assessed in each spot, and an average value was calculated per case. Pairwise correlation coefficients (CC) were estimated for all markers. Strength of correlation was interpreted as follows: < 0.3, weak; 0.3–0.5, moderate; > 0.5, strong.
Results: Extent of p16INK4a expression was positively correlated with Ki-67 (CC = 0.39, P < .001) and negatively correlated with p53 (CC = –0.28, P = .003) and cyclin-D1 (CC = –0.48, P < .001). In addition, extent of p53 expression was positively correlated with Ki-67 (CC = 0.22, P = .02) and cyclin-D1 (CC = 0.48, P < .0001). Cyclin-D1 intercorrelation with p16INK4a and p53 was similar accross histologic subtypes of penile cancer. No significant associations were found for all the other pairwise correlations. Tumors with warty and/or basaloid morphology had higher levels of p16INK4a and Ki-67 (both P = .001) compared to keratinizing SCC.
Conclusions: Increased Ki-67 was positively correlated with the expression of both p16INK4a and p53. The negative correlation between p16INK4 and cyclin-D1 is expected. The positive correlation between cyclin-D1 and p53 and the negative correlation between p16INK4a and p53 indicates a crosstalk between pathways during penile carcinogenesis. This crosstalk seems to be independent of tumor morphology.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 146, Monday Afternoon