Abstract 5709: Variation in Merlin expression and its prognostic significance in malignant pleural mesothelioma
Authors: Dhakal Ajay , Pokharel Saraswati , Wang Katy , Demmy Todd , Nwogu Chukwumere E. , Yendamuri Sai S. , Dy Grace 
Published: July 2017

Introduction:

Malignant Pleural Mesothelioma (MPM) is an aggressive cancer with overall survival (OS) of about 8 months. Prognostic biomarkers allowing for biology-driven individualized therapies are lacking in MPM. Alterations in a tumor suppressor gene NF-2 are seen in 20-40% of MPM. NF-2 encodes for Merlin, which suppresses tumorigenesis by regulating pathways like mTOR and Hippo. Merlin status had been proposed as a predictive biomarker for treatment with the focal adhesion kinase (FAK) inhibitor. The purpose of our study is to examine differences in Merlin expression among histologic subtypes of MPM and its prognostic impact on clinical outcome.

Materials and Method:

48 cases of MPM from 1993-2013 with available archival tissues were identified. H/E stained sections were reviewed by a pathologist and categorized into 3 histologic subtypes, namely epithelioid (E), sarcomatoid (S) and biphasic (B). Immunohisochemistry-based Merlin expression score from 0 to 3 were given to the samples, accounting for both intensity and frequency of staining. Chart review was performed to obtain clinical data. Kruskal-Wallis Test was used to compare mean Merlin scores, and Logrank test was used to compare OS between low Merlin (LM, &lt;3) and high Merlin (HM, 3) groups.

Results:

Mean age of patients was 66.75 years (HM 64.58, LM 68.92). Other demographic profile (HM%, LM%) included male sex 89.5% (51, 49), current or past smokers 66.6% (47, 53), current or past Asbestos exposure 71% (35, 65), resectable disease 89% (51, 49), stages 3 or 4 disease 64% (56, 44), and 85% (56, 44) received surgery. Mean Merlin scores among 3 histologic types were different (Mean, Std. Dev: B 2.25, 0.48; E 2.74, 0.54; S 2.56, 0.53; p= 0.0037). Mean Merlin score of E component was significantly higher than that of S component within B MPM (E 2.75, 0.45; S 1.75, 0.68; p&lt;0.0001). Interestingly, mean Merlin score of S was significantly higher than that of S component of B MPM (S 2.56, 0.53; B 1.75, 0.68; p=0.005) making S component of B MPM least Merlin expresser. There was no significant difference in response rate to platinum and in progression-free survival between LM and HM. Median OS (months) for LM was 8.8 compared to 12.9 for HM (p=0.0262). Among different variables analyzed (age, sex, smoking history, histology, and upfront treatment modalities), age was associated with OS. After controlling for age, there was no statistically significant difference in OS between LM and HM (p=0.11).

Conclusion:

Merlin expression level is different among E, S and B MPMs. Moreover, it is significantly lower in S component of B MPM than S. Its prognostic ability appears to be confounded by the association with age in our cohort. A larger study is needed to further explore the prognostic impact of this biomarker.

Citation Format: Ajay Dhakal, Saraswati Pokharel, Katy Wang, Todd Demmy, Chukwumere E. Nwogu, Sai S. Yendamuri, Grace Dy. Variation in Merlin expression and its prognostic significance in malignant pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5709. doi:10.1158/1538-7445.AM2017-5709