[681] Esophageal Adenocarcinoma Shows Upregulation of Skp2 and Cks1 and Downregulation of p27

JY Liu, AM Bellizzi, IS Hatzaras, M Bloomston, WL Frankel. Ohio State University, Columbus, OH; Brigham and Women's Hospital, Boston, MA

Background: P27 is a cyclin dependent kinase inhibitor involved in cell cycle regulation. Skp2 and Cks1 are components of the complex responsible for ubiquitylation of p27, leading to its subsequent proteosomal degradation. P27, Skp2 and Cks1 have been implicated in cancer development. We compared these proteins in esophageal adenocarcinoma (Ad), Barrett esophagus with dysplasia (BD) and without dysplasia (B), and normal glands (NG) to investigate their role in carcinogenesis.
Design: Archival files were searched for esophageal Ad resections. 63 cases were reviewed and cores were taken from Ad (63), BD (22), B (23), and NG (35). Tissue microarrays with 2 cores per area, 2.0 mm each were constructed. Sections were stained for p27, Skp2 and Cks1 and evaluated for percentage of positive staining and intensity (1, weakly positive and 2, strongly positive). A score was determined by multiplying percentage by intensity. Statistical analyses were performed using Mann Whitney U test, Cox regression, and Pearsons correlation.
Results: Skp2 and Cks1 were significantly upregulated in Ad, BD and B as compared to NG (p<0.001), while Cks1 was also significantly increased in BD compared to B (p<0.001). P27 was significantly downregulated in Ad as compared with all other groups (p<0.001). Expression of Cks1 and Skp2 directly correlated (r=0.46, p=0.0001), while the correlation of p27 to Cks1 and Skp2 was not statistically significant. Survival did not correlate with any markers.

Expression of p27, Skp2 and Cks1

	Normal Glands	Barrett	Barrett with Dysplasia	Adenocarcinoma
p27 (mean SD)	44.6 ±119	20.7 ±21.4	36.2 ±45.1	5.6 ±11
Skp2 (mean SD)	1.4 ±2.8	14.3 ±23.1	20.4 ±26.8	35.9 ±31.5
Cks1 (mean SD)	4.4 ±4.4	19.6 ±17.7	61.1 ±42.8	59 ±42

Mann Whitney U Test

	NG vs. B	NG vs. BD	NG vs. Ad	B vs. BD	BD vs. Ad
p27	0.8372	0.7084	<0.0001	0.7689	0.0006
skp2	<0.0001	<0.0001	<0.0001	0.0923	0.3
Cks1	<0.0001	<0.0001	<0.0001	0.0008	0.9

Conclusions: Skp2 and Cks1 are overexpressed in Ad, BD and B suggesting they play an early role in the progression to B and Ad. P27 was only downregulated in Ad indicating that it is involved in later stages of carcinogenesis. Additional studies are warranted to elucidate the mechanism of p27 downregulation in esophageal Ad.
Category: Gastrointestinal

Wednesday, March 24, 2010 9:30 AM

Poster Session V # 78, Wednesday Morning