Does SPOP-Mutated Prostate Cancer Have Specific Morphology?
Kevin R Turner, Kyung Park, Sylvan Bacca, Ya-Lin Chiu, Christopher Barbieri, Francesca Demichelis, Levi Garraway, Mark Rubin, Juan Miguel Mosquera. Weill Medical College of Cornell University, New York, NY; The Broad Institute of Harvard and MIT, Cambridge, MA; Harvard Medical School, Boston, MA
Background: Recurrent inactivating mutations of the SPOP gene are present in 14% of whole exome-sequenced prostate cancer (PCa), making it the most common mutation in this type of cancer thus far. Most recent data from our group suggests that SPOP mutations define a distinct molecular class of ETS-negative prostate cancer with aggressive behavior and potential therapeutic targets. We sought to determine if this common mutation is associated with a morphological phenotype.
Design: Whole-exome sequencing was performed in 118 unselected PCa cases from one institution. Of these, 11 (9.3%) demonstrated SPOP gene mutation. Blinded to mutation status, two reviewers assessed all prostatectomy slides from 11 SPOP-mutated cancers and 11 non-SPOP-mutated cases with similar Gleason scores and pathologic stage. Dominant and secondary tumor nodule(s) from each prostatectomy specimen were assessed for presence or absence of 15 morphological features of PCa: Intraductal spread, cribriform morphology, blue-tinged mucin, crystalloids, high nucleocytoplasmic ratio, macronucleoli, foamy gland features, collagenous micronodules, small cell/neuroendocrine differentiation, perineural invasion, extraprostatic extension, signet-ring like cell features, ductal morphology, glomerulations, and comedonecrosis. To identify associations between morphology and SPOP mutation-positive status, Fisher's exact tests were performed with p-values corrected for multiple comparisons using the step-down Bonferroni method.
Results: No morphologic features were associated with SPOP mutated PCa. The cribriform morphology, while not statistically significant, was present in 64% of SPOP mutants compared to 18% of non-mutants (p = 0.08). Foamy gland morphology showed a significant negative association with SPOP mutation, with 18% of SPOP mutated cases exhibiting this feature compared to 72% of control cases (p = 0.03). However, when p-values were adjusted to account for multiple comparisons, the statistical significance of this finding was lost.
Conclusions: This study is the first to examine morphological features of PCa harboring SPOP mutations. Foamy gland morphology was less commonly identified in SPOP mutated cases; while cribriform morphology was more commonly identified in SPOP mutated cases when compared with controls. Future studies employing a larger sample size will be required to establish whether these preliminary findings are statistically significant.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 8:15 AM
Platform Session: Section A, Tuesday Morning