Tumoral CD10 expression correlates with high-grade histology and increases risk of recurrence in patients with stage I lung adenocarcinoma.

Abstract

CD10 (neutral endopeptidase) is expressed in various normal and tumor cells, and its biological function can be controlled through enzymatic activity and signaling pathways. We investigated whether CD10 expression predicted disease recurrence and whether it correlated with histologic subtypes of stage I lung adenocarcinoma. We reviewed tumor slides of resected pathologic stage I lung adenocarcinomas (1995-2009). Tumors were classified according to the IASLC/ATS/ERS classification. CD10 immunohistochemistry was performed using tissue microarrays (n=915). We combined the intensity (0-3) and distribution scores (0-2) for CD10 to create a total score (0-5). Risk of recurrence was estimated using competing risks methods. In the training cohort (n=313), risk of recurrence of patients with high tumoral CD10 (score>1, n=57) was significantly higher (5-year cumulative incidence of recurrence [CIR], 37%) than in those with low CD10 (score≤1; n=256; 5-year CIR, 16%; P<0.001); this finding was confirmed in the validation cohort (n=602, P=0.036). High tumoral CD10 was associated with higher risk of recurrence in acinar (P=0.007) and papillary predominant tumors (P=0.022). High tumoral CD10 was most frequently identified in micropapillary predominant (41%) and solid predominant tumors (34%). On multivariate analysis of intermediate-grade tumors, high tumoral CD10 remained a significant independent risk factor of recurrence (hazard ratio, 1.88; P=0.025). In stage I lung adenocarcinoma, tumoral CD10 correlated with high-grade histology and was an independent predictor of recurrence in intermediate-grade tumors.