The diffusing capacity of the lung for carbon monoxide is associated with the histopathological aggressiveness of lung adenocarcinoma†

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The diffusing capacity of the lung for carbon monoxide (DLCO) is an indicator of lung damage. We sought to determine whether DLCO is associated with the aggressiveness of lung adenocarcinoma using histopathological indexes, such as tumour differentiation, scar grade, nuclear atypia and the mitotic index. Fifty-seven patients with low DLCO (≤80% of predicted) and 466 patients with normal DLCO (>80% of predicted) who underwent R0 resection of lung adenocarcinoma between 2005 and 2012 were retrospectively reviewed. The relationships between the DLCO status and each histopathological index as well as the overall survival were evaluated. Low DLCO had significant relationships with moderate/poor differentiation (79% vs 57% [low DLCO vs normal DLCO]), scar grade 3/4 (37% vs 18%), nuclear atypia 3 (65% vs 30%) and the mitotic index 3 (26% vs 8%). After adjusting for the age, sex, forced expiratory volume in 1 s, smoking status and tumour size, a low DLCO still showed a significant correlation with the histopathological indexes. These histopathological indexes were all significant factors for the overall survival on log-rank tests. In a multivariable Cox regression analysis with 13 clinicopathological variables, moderate/poor differentiation and nuclear atypia Grade 3 were significant histopathological factors for the overall survival (hazard ratios: 2.16 and 1.84; 95% confidence intervals: 1.10-4.51 and 1.06-3.21; P = 0.024 and 0.029, respectively). Our findings regarding the relationship between DLCO and the histopathological indexes of lung adenocarcinoma suggest that lung damage may be associated with carcinogenesis and progression.