NaPi2b expression in a large surgical Non-Small Cell Lung Cancer (NSCLC) cohort

Abstract Background NaPi2b is a multi-transmembrane sodium-dependent phosphate transporter expressed at normal levels in several organs, including lung. High expression levels have been reported in various tumours including breast, thyroid, ovarian and non-small cell lung cancer. To date evaluation of NaPi2b expression has mostly been restricted to smaller lung cancer cohorts. Methods Analyses were performed on archival formalin fixed paraffin embedded primary tumour specimens from patients who had undergone curative intent resection at an Australian tertiary hospital. Tissue microarrays were constructed and stained with the chimeric anti-NaPi2b antibody, MERS67. Semi-quantitative H-scores (range 0 – 300) were calculated for each core tissue sample (H-score = % tumour cells staining for NaPi2b multiplied by staining intensity). An overall average H-score was reported for each specimen, with a cut-off score of 50 considered positive. Results Of 438 cases, high NaPi2b expression was observed in 151 (34.5%) overall, high expression in 137/208 (65.9%) adenocarcinoma cases, and 5/179 (2.8%) squamous cases (p Conclusion High NaPi2b expression was noted in a significant subset of adenocarcinoma cases, and in particular amongst those who were TTF1+, or exhibited EGFR or KRAS mutations. This agrees with earlier reports and highlights the significance that NaPi2b may have a role as a possible target for delivery of cytotoxic agents via antibody-drug conjugate models for some patients with lung adenocarcinoma. Micro Abstract Retrospective analysis of NaPi2b expression amongst 438 resected non-small cell lung cancer specimens. High NaPi2b expression noted in 34.5% cases overall and 65.9% of adenocarcinoma cases. Early phase clinical trials with antibody drug conjugates utilising NaPi2b are currently in progress in non-small cell lung cancer cohorts.