Immunohistochemical Differences between Pancreatic Adenocarcinoma and Intraductal Papillary Mucinous Neoplasms: Insights into Progression of a Precursor Lesion
Andrew T Turk, Dario Garcia-Carracedo, Gloria Su, John Chabot, Helen Remotti. Columbia University, New York, NY
Background: Alteration of p16, p53, PTEN, and Bcl2 occur frequently in pancreatic adenocarcinoma (PCa). Recent studies have demonstrated p16, p53, Bcl2, and Ki67 as prognostic immunohistochemical (IHC) biomarkers of PCa. Intraductal papillary mucinous neoplasms (IPMN) represent precursor lesions that can progress to PCa. The molecular alterations that mediate progression from IPMN to PCa, and the differences between these lesions in terms of IHC, remain poorly understood. We have previously reported the PTEN, p53, and p16 IHC profile of 36 IPMN cases. In this study, we characterize the differences between these IPMN cases and 19 PCa cases, in terms of p16, p53, PTEN, Bcl2, and Ki67 IHC.
Design: We analyzed 36 cases of IPMN and 19 cases of PCa. DNA was extracted from paraffin-embedded tissue. Tissue microarrays consisting of 3 cores/case were constructed. Expression of p16, p53, PTEN, Bcl2, and Ki67 was assessed by IHC. PTEN expression within lesional epithelium was scored as normal (2+), decreased (1+), or negative (0). Bcl2 expression was scored as increased (2+) or normal (1+) compared to non-neoplastic epithelium. Staining for p53 (0,1+,2+,3+) and p16 (0,1+,2+) was scored according to intensity. Ki67 positivity was scored as a percentage.
Results: We observed significant differences in terms of p53 and PTEN IHC between PCa (p53=1.02/3; PTEN=0.36/2) and IPMN (p53=0.48/3; PTEN=1.47/2) (p<0.05). No significant differences were observed between PCa and IPMN in terms of p16 (IPMN=0.65/2; PCa=0.45/2), Bcl2 (IPMN=1.37/2; PCa=1.36/2), or Ki67 (IPMN=14%; PCa=15%). Differences in p53, PTEN, and p16 staining were significant when low-grade (LG) and intermediate-grade (IG) IPMN (p53=0.33/3; PTEN=1.70/2; p16=0.89/2) were compared to high-grade (HG) IPMN and PCa (p53=0.83/3; PTEN=0.80/2; p16=0.43/2) (p<0.05).
Conclusions: The observed differences between IPMN and PCa in terms of p53 and PTEN staining suggest that PTEN loss and decreased p53 function contribute to the progression from IPMN to PCa. The observed differences between LG and IG IPMN versus HG IPMN and PCa indicate roles for p16, p53, and PTEN in the evolution of HG IPMN, prior to the development of cancer. We did not observe differences in Bcl2 IHC, perhaps because alterations of Bcl2 occur early in the development of IPMN, or cannot be detected by IHC. These findings provide insight into molecular changes that mediate the progression of IPMN into PCa.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 135, Tuesday Morning