Abstract A043: NaPi2b expression in a large surgical non-small cell lung cancer cohort
Authors: Mitchell Paul L , Yu Hui , Rivalland Gareth , Asadi Khashayar , Mosher Rebecca , Hirsch Fred , Rivard Christopher 
Published: March 2020

Abstract
Background: NaPi2b (SLC34A2) is a sodium-dependent phosphate transporter expressed in a high proportion of non-small cell lung cancer (NSCLC), especially adenocarcinoma, and ovarian carcinoma cases, as well as other tumour types. A clinical trial of the NaPi2b-targeting antibody drug conjugate XMT-1536 is currently underway. This study investigates NaPi2b expression in NSCLC emphasising correlations to histology. Methods: Tissue Microarrays (TMAs) were constructed using triplicate 1mm cores from FFPE primary NSCLC tumours resected by lobectomy or pneumonectomy with curative intent at Austin Health, Melbourne, Australia. Pathology review identified the best site for coring of tumour blocks. For IHC, TMAs were stained with an anti-human NaPi2b primary antibody (MERS67) on the Leica Bond RX auto-stainer and the H-score (0 – 300) calculated based on the percentage of tumour cells stained multiplied by the staining intensity (0 - 3+). The mean score of multiple cores was calculated. A high H-score was defined as ≥50. Results: High NaPi2b expression was seen in 153/439 (35%) of cases. High NaPi2b expression was determined in 132/215 (61%) of adenocarcinoma cases, while only 12/178 (7%) of squamous cell and 9/46 (20%) of other histology cases (p &lt; 0.001, chi-square) had high expression. Considering adenocarcinoma subtypes, high NaPi2b was seen with 18/21 (86%) micropapillary, 35/61 (57%) solid, 3/13 (23%) mucinous, 54/84 (64%) acinar, 8/13 (62%) papillary, 9/9 (100%) lepidic and 3/9 (33%) adenosquamous. Overall high NaPi2b was seen in 56/95 (59%) with poor risk adenocarcinoma subtypes (micropapillary, solid, mucinous) and 71/106 (67%) with good risk subtypes (papillary, acinar, lepidic). High scores were more frequent for females (52% vs 27%; p &lt; 0.001), never smokers vs smokers (63% vs 33%; p &lt; 0.001), EGFR mutation vs wt (75% vs 22%; p &lt; 0.001) and KRAS mutation vs wt (71% vs 22%; p &lt; 0.001). There were no significant differences in expression considering stage, primary tumour diameter, FEV1 (% predicted) or level of PD-L1 expression. For the whole cohort, a high NaPi2b score was associated with improved overall survival on univariate analysis (median 58 months vs 36 months; HR 0.77 [95% CI 0.61-0.97], p=0.03), while for adenocarcinoma there was a trend for improved survival (median 54 months vs 35 months; HR 0.76 [95% CI 0.55-1.04], p=0.09), and for both high risk adenocarcinoma subtypes (micropapillary, solid) and good risk subtype (acinar), high NaPi2b expression was associated with a weak trend to better survival. On multivariable analysis, NaPi2b remained the strongest predictor of improved survival (HR 0.77, 95% CI 0.58 - 1.02, p=0.07), though stage remained the only statistically significant variable. Conclusion: In this large early stage surgical NSCLC cohort, a high level of NaPi2b expression was seen with adenocarcinoma histology and also across the range of adenocarcinoma subtypes. Female gender, never smokers, and EGFR mutations were independently predictive of high level expression. For the whole cohort, high level expression was associated with improved overall survival. There was a similar, but non-significant, trend for high level expression in adenocarcinoma cases to be associated with improved survival, which appeared to be the case for both high risk and good risk adenocarcinoma subtypes.
Citation Format: Paul L Mitchell, Hui Yu, Gareth Rivalland, Khashayar Asadi, Rebecca Mosher, Fred Hirsch, Christopher Rivard. NaPi2b expression in a large surgical non-small cell lung cancer cohort [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A043. doi:10.1158/1535-7163.TARG-19-A043