Comparison of Different Hepatocyte Nuclear Factor 4 Clones for Invasive Mucinous Adenocarcinoma of the Lung

Invasive mucinous adenocarcinoma (IMA) is a rare variant of adenocarcinoma that comprises mucinous epithelial cells. The expression of hepatocyte nuclear factor 4 alpha (HNF4 alpha) has been previously reported as a marker for IMA, but controversy remains regarding whether HNF4 alpha is a reliable marker for lung IMAs. In the present study, we compared HNF4 alpha expression levels between IMA and nonmucinous adenocarcinoma (NMA) cases using 2 different HNF4 alpha clones. We used 2 HNF4 alpha antibody clones, H1 and H1415, to examine HNF4 alpha expression in 36 IMA and 40 NMA cases, which comprised the control group. HNF4 alpha immunostaining intensity (range, 0 to 3) and percentage of intensity (range, 0% to 100%) were evaluated by 3 pathologists and ImageJ software, and average H-scores were calculated for each case. Interobserver agreement was assessed using intraclass correlation coefficient. Receiver-operating characteristic curve was used to analyze sensitivity and specificity of the clones. The mean H-score was higher in the IMA group than in the NMA group for both the H1415 (141.3 vs. 9.3) and H1 (67.3 vs. 3.4) clones. The intraclass correlation coefficient for agreement among the 4 observers was good (0.806 and 0.711). The H1415 clone exhibited comparable sensitivity (83.3% vs. 83.3%) with higher specificity (97.5% vs. 92.5%) compared with the H1 clone when using cutoff values of 36.2 (H1415) and 9.5 (H1), respectively. Our analyses suggest that HNF4 alpha should be considered as a reliable marker for primary IMA of the lung. The H1415 clone should be preferred for use in clinical practice.