[1838] Nuclear Expression of PTEN in Endometrial Carcinoma

Bojana Djordjevic, Russell Broaddus. University of Ottawa, Ottawa, ON, Canada; MD Anderson Cancer Center, Houston, TX

Background: PTEN protein is a tumor suppressor which negatively regulates the PI3K–AKT signaling pathway via its cytoplasmic phosphatase function, and its loss is implicated in the pathogenesis of endometrial carcinoma (EC). Nuclear presence of the PTEN protein was recently found in cell lines to also have tumor suppressive activity via a mechanism independent of phosphatase activity. The purpose of this study was to characterize the nuclear vs. cytoplasmic expression of PTEN in a set of EC in which the PTEN mutation status is known.
Design: 154 EC cases consisting of 100 endometrioid and 54 non-endometrioid carcinomas were subjected to PTEN IHC analysis as well as to full-length PTEN gene sequencing to detect mutations. The PTEN antibody was previously validated on cancer cell lines. Cytoplasmic IHC staining was scored as positive (Cyto-pos:>90% of tumor with diffuse cytoplasmic staining), negative (Cyto-neg: 0% of tumor cells staining) and heterogeneous (Cyto-het: distinct positive and negative foci). Nuclear IHC staining was scored as positive (Nuclear-pos: >10% of tumor cells) or negative (Nuclear-neg: ≤ 10%).
Results:

 Cyto-neg, Nuclear-negCyto-pos or het, Nuclear-negCyto-pos or het, Nuclear-pos
ENDOMETRIOID n=100
PTEN mutation36132
PTEN wild type211414
NON-ENDOMETRIOID n=54
PTEN mutation843
PTEN wild type61716


Nuclear PTEN expression, if present, was always observed concurrently within areas of cytoplasmic expression. In particular, no cases showed positive nuclear and negative cytoplasmic PTEN staining. Among ECs with a wild type PTEN, both endometrioid (50%) and non-endometrioid (48%) tumors showed similar frequencies of nuclear PTEN expression. In endometrioid ECs with a mutated PTEN and with cytoplasmic PTEN expression, a greater proportion (80%) of cases lacked nuclear expression compared to non-endometrioid ECs (20%).
Conclusions: Endometrioid ECs with a PTEN mutation and cytoplasmic PTEN expression preferentially lack nuclear staining and hence the nuclear tumor suppressor function of PTEN. Cytoplasmic expression in these cases may be secondary to retention of a non-functional PTEN protein. Interestingly, approximately 50% of PTEN wildtype EC with cytoplasmic PTEN protein expression, have loss of nuclear expression and thus loss of nuclear tumor suppressive function. In these tumors, cell proliferation may still be driven by the PI3K-AKT pathway through mutations in PIK3CA or other pathway members besides PTEN, or by upregulation of other signaling pathways.
Category: Pathobiology

Monday, March 4, 2013 1:00 PM

Poster Session II # 264, Monday Afternoon

 

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