CDKN2A and MTAP Deletions in Peritoneal Mesotheliomas: Correlation with Loss of p16 Protein Expression and Survival
AM Krasinskas, D Bartlett, K Cieply, S Dacic. University of Pittsburgh, Pittsburgh, PA
Background: Homozygous deletion of CDKN2A is one of the most common genetic alterations in pleural mesotheliomas, occurring in 74% of cases. MTAP resides in the same gene cluster of the 9p21 region and is co-deleted in the majority of CDKN2A deleted cases. Correlation with p16 immunostaining is variable. This study examines the genetic alterations in peritoneal mesotheliomas, which may have a different pathogenesis than their pleural counterparts.
Design: 25 cases of peritoneal mesotheliomas in a triplicate tissue microarray were studied. Dual-color FISH was performed using a CEP9 probe and either a CDKN2A or MTAP locus-specific probe. Cases with >20% of nuclei lacking both signals for the locus-specific probe and having at least one signal for CEP9 were considered homozygous deleted. Cases with nuclear p16 immunostaining in <5% of cells were considered negative. Fisher exact tests were used unless specified.
Results: 8 of 25 (32%) peritoneal mesotheliomas had homozygous deletion of CDKN2A; MTAP was co-deleted and p16 protein expression was lost in every case.
Table 1.Ep = epithelial; Sarc = sarcomatoid
|Number||M/F||Mean Age||Ep/Sarc||MTAP deletion||p16 loss|
|No CDNK2A deletion||17||13/4||51||16/1||1||5|
|p = NS||p = 0.028 (T-test)||p = NS||p<0.00001||p = 0.001|
Patients with CDKN2A deletions had worse overall and disease free survival (p=0.042 & p=0.018, respectively; Kaplan-Meier).
Conclusions: Similar to pleural mesotheliomas, patients with CDKN2A deletion had significantly worse survival. Detection of CDKN2A/MTAP co-deletion in peritoneal mesotheliomas coupled with a p16 stain as an inexpensive screening tool, can identify those patients with a worse prognosis and possible response to targeted therapy of the MTAP/AMP pathway.
Monday, March 9, 2009 1:00 PM
Poster Session II # 94, Monday Afternoon