Evaluation of Prognostic Markers in Metastatic Well-Differentiated Neuroendocrine Tumors to the Liver
Zhaohai Yang, Laura H Tang, David S Klimstra. Penn State Milton S. Hershey Medical Center, Hershey, PA; Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Well-differentiated neuroendocrine tumor (NET) is a heterogeneous group. Current WHO classification stratifies those tumors into two histologic grades (G1 and G2) based on mitotic activity or Ki67 labeling index, whose prognostic value has been validated in both primary and metastatic tumors. Additional markers were suggested to have prognostic significance in various primary NETs, but their roles in metastatic disease had not been tested.
Design: Tissue microarray was constructed from 42 surgically resected metastatic well-differentiated NETs to the liver. Immunohistochemical staining for p27Kip1, CK19, CD117, PAX8 and CD99 was performed and the staining was scored in a semiquantitative manner. The positivity of each marker was compared to the histologic grade determined previously by Ki67 labeling index, and their prognostic significance was analyzed using the Kaplan-Meier estimate.
Results: Most metastatic NETs were positive for p27Kip1 (97.6%); while negative for PAX8 and CD99 (92.9% negative in each). A subset of the tumors showed positive staining for CK19 (64.3%) or CD117 (33.3%). We found no correlation between the positivity of any of the above markers and the histologic grade based on Ki67 labeling index. Upon Kaplan-Meier survival analysis, there was no difference in patient survival based on the expression of p27Kip1, CK19, PAX8 or CD99. CD117-negative patients showed slightly better overall survival than CD117-positive ones (70.8% vs. 40.4% five-year survival; or 103 vs. 47 months of median survival); however, the difference did not reach statistical significance (p=0.16).
Conclusions: Although p27Kip1, CK19, CD117, PAX8 and CD99 may have prognostic significance in some primary well-differentiated NETs, no correlation with patient survival or tumor grade was found in metastatic tumors. The small survival difference between CD117-negative and CD117-positive groups seen in our study needs to be further tested in a larger cohort.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 242, Tuesday Afternoon