New research has found that high levels of NaPi2b expression are prevalent in adenocarcinoma histology, as well as across a range of adenocarcinoma subtypes in patients with early stage, surgical non small-cell lung cancer (NSCLC).
The study also found that high levels of NaPi2b expression were associated with improved overall survival in these individuals.
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In a presentation here at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (abstract A043), the multi-center research team explained that NaPi2b is a sodium-dependent phosphate transporter that is expressed in a high proportion of NSCLC, particularly adenocarcinoma. In the current investigation, they examined NaPi2b expression in NSCLC, with a particular emphasis on correlations with histology.
To do so, they constructed tissue microarrays using triplicate 1-mm cores from NSCLC tumors that had been resected by either lobectomy or pneumonectomy. Pathology review identified the best site for coring the tumor blocks.
As part of the immunohistochemical analysis, tissue microarrays were stained with an anti-human NaPi2b primary antibody (MERS67). Afterwards, the H-score (0-300) was calculated based on the percentage of tumor cells stained and the staining intensity (0-3+). The mean score of multiple cores was calculated; high H-scores were defined as those ≥50.
The investigators -- led by Paul Mitchell, MD, a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Melbourne, Australia -- found that high NaPi2b expression was seen in 35% of all cases (153/439). Interestingly, such high expression was observed in 61% (132/215) of adenocarcinoma cases, but only 7% (12/178) of squamous cell cases and 20% (9/46) of other histology cases (p<0.001).
With respect to specific adenocarcinoma subtypes, high NaPi2b expression was observed in:
86% (18/21) of micropapillary cancers;
57% (35/61) of solid cancers;
23% (3/13) of mucinous cancers;
64% (54/84) of acinar cancers;
62% (8/13) of papillary cancers;
100% (9/9) of lepidic cancers; and
33% (3/9) of adenosquamous cancers.
In total, high NaPi2b expression was seen in 59% (56/95) of individuals with high-risk adenocarcinoma subtypes, (such as micropapillary, solid, mucinous), compared with 67% (71/106) of their counterparts with good-risk subtypes (papillary, acinar, lepidic).
Female gender, never smokers, and EGFR mutations were independently predictive of high-level expression. Specifically, the study also found that high H-scores were more frequent in females than in males (52% vs 27%; p<0.001); in never-smokers than in smokers (63% vs 33%; p<0.001); in patients with EGFR mutation than in those with wild-type EGFR mutations (75% vs 22%; p<0.001); and in patients with KRAS mutation than in those with wild-type KRAS mutations (71% vs 22%; p<0.001).
No significant differences in expression were found with respect to stage, primary tumor diameter, forced expiratory volume in 1 second (FEV1), or level of PD-L1 expression.
Univariate analysis of the entire cohort revealed that patients with high NaPi2b scores boasted overall median survival of 58 months, significantly longer than the median of 36 months among their counterparts who did not have such high scores (hazard ratio 0.77; p=0.03).
A similar trend for improved survival was seen for adenocarcinoma (median 54 months vs 35 months; HR 0.76; p=0.09), though this did not reach statistical significance. Similarly, among both high-risk adenocarcinoma subtypes (micropapillary, solid) and good-risk adenocarcinoma subtypes (acinar), high NaPi2b expression was associated with a weak trend toward better survival.
The researchers also performed multivariable analysis, which demonstrated that 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.
In light of these findings, the investigators concluded that high levels of NaPi2b expression were associated with adenocarcinoma histology, and across the range of adenocarcinoma subtypes.
“For the whole cohort, high-level expression was associated with improved overall survival,” the authors wrote. “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.”