Abstract 4331: Menacalc as an independent prognostic factor and predictor of metastasis in Non-Small Cell Lung Cancer
Authors: Gustavson Mark , Davis Wendy , Bronsther Oscar , Gertler Frank 
Published: August 2015

The Mena protein has been shown to be critical for breast cancer metastasis, and, in pre-clinical models two of its isoforms MenaINV and Mena11a are expressed in invasive and non-invasive tumor cell subpopulations, respectively. We have previously developed a quantitative immunofluorescence approach to assess the fraction of Mena protein lacking Mena11a called Menacalc as a method to infer presence of invasive tumor cells. Menacalc is determined by subtracting the population-based Z-score (quantifies the relationship to the mean) for Mena11a quantitative expression score from the population-based Z-score for total Mena quantitative expression score. The resulting Menacalc scores range from -4 to +4 with high scores reflecting tumors with relatively high total Mena (all isoforms) but low Mena11a. We showed that high MENAcalc scores associated significantly with poor disease-specific survival in breast cancer patients, including node-negative and positive cases. A recent study reported that a semi-quantitative approached to Mena assessment shows prognostic value in early Non-Small Cell Lung Cancer (NSCLC) (Bria et. al 2014). Here, we asked whether the quantitative Menacalc assay has prognostic value in NSCLC and if it can predict metastatic disease. We determined Menacalc on a cohort of 201 predominantly early-stage NSCLC cases using multiplexed quantitative immunofluorescence (MQIF) and then assessed Menacalc with respect to clinical and pathological features, as well as disease-specific survival. There was no significant difference in Menacalc by stage, sex, or age. However, Menacalc was significantly higher (P = 0.001) in squamous cell carcinoma (N = 32) as compared to other histological subtypes. High levels of Menacalc were associated (10% significance level) with decrease 5-year disease specific survival in all patients [HR = 1.78 (95%CI: 0.92-3.43); P = 0.08], and were significantly associated with survival when either corrected for histological subtype [HR = 2.10 (95%CI: 1.04-4.26); P = 0.04] or in the squamous-only population [HR = 6.60 (95%CI: 1.22-53.75); P = 0.04]. There was no difference in survival as a function of stage nor in adenocarcinomas. Furthermore, consistent with Mena isoform status being associated with the metastatic phenotype, Menacalc was 2-fold higher (P = 0.09) in metastatic patients, but the sample size with available clinical data was limited (N = 9). Taken together, these data demonstrate that Menacalc has potential prognostic value especially in squamous cell carcinoma patients. These data also preliminarily suggest that Menacalc can predict the metastatic phenotype. Further studies examining Mena isoform expression in squamous and later-stage metastatic NSCLC patients is thus warranted and currently ongoing.

Citation Format: Mark Gustavson, Wendy Davis, Oscar Bronsther, Frank Gertler. Menacalc as an independent prognostic factor and predictor of metastasis in Non-Small Cell Lung Cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4331. doi:10.1158/1538-7445.AM2015-4331