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

• Published in: Clinical lung cancer Vol. 23; no. 2; pp. e90 - e98
• Main Authors: Heynemann, S, Yu, H, Churilov, L, Rivalland, G, Asadi, K, Mosher, R, Hirsch, F, Rivard, C, Mitchell, P
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2022
• Subjects: Aged; antibody-drug conjugate; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Cohort Studies; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry - methods; lung adenocarcinoma; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Middle Aged; non-small cell lung cancer; Prognosis; Sodium-Phosphate Cotransporter Proteins, Type IIb - metabolism; targeted therapy; non-small cell lung cancer; targeted therapy; antibody-drug conjugate; lung adenocarcinoma
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2021.11.005

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 tumors 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.
Analyses were performed on archival formalin fixed paraffin embedded primary tumor 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 = % tumor 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.
Of 438 cases, high NaPi2b expression was observed in 151 (34.5%) overall, high expression in 137 of 208 (65.9%) adenocarcinoma cases, and 5 of 179 (2.8%) squamous cases (P < .0001). High NaPi2b expression was associated with female sex, EGFR or KRAS mutation, and TTF1 positivity (adenocarcinoma cases only). High NaPi2b expression was associated with improved overall survival (median 54 vs. 35 months, P = .029).
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.
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 utilizing NaPi2b are currently in progress in non-small cell lung cancer cohorts.