Correlation of Immunohistochemistry and Mutation Status of PTEN in Endometrial Carcinoma
B Djordjevic, B Hennessy, R Broaddus. M.D. Anderson Cancer Center, Houston, TX
Background: PTEN is a tumor suppressor that negatively regulates the PI3K signaling pathway, which has been implicated in the pathogenesis of endometrial carcinoma, with PTEN mutations occurring at high frequency. With the advent of targeted therapy and PI3K inhibitors entering clinical trials, gynecologic pathologists must accurately identify endometrial cancer patients that may benefit from these new treatments. However, PTEN mutations are highly variable in type, and their detection necessitates the use of full-length sequencing, which cannot be feasibly employed in routine clinical practice. The aim of this study was to evaluate the fidelity of immunohistochemistry (IHC) for PTEN as a surrogate for assessment of PTEN mutation status.
Design: A cohort of 156 tumors comprised of 101 endometrioid and 55 non-endometrioid cases was subjected to full-length PTEN sequencing to detect mutations as well as PTEN IHC analysis. The antibody was previously validated on cancer cell lines known to be PTEN positive or negative. IHC staining was scored as positive (>90% of tumor with diffuse cytoplasmic staining), negative (0% of tumor cells staining) and heterogeneous (distinct positive and negative foci). Adjacent normal tissue was used as an internal positive control.
Results: PTEN mutation status and immunohistochemistry are summarized in the table below.
|IHC||Mutation Detected||Mutation Not Detected||Total|
|Negative||25 (68%)||45 (38%)||70 (45%)|
|Heterogenous||6 (16%)||21 (18%)||27 (17%)|
|Positive||6 (16%)||53 (44%)||59 (38%)|