Impact of CA9 expression in the diagnosis of lymph-node metastases in non-small cell lung cancer based on [18F]FDG PET/CT

Abstract

Background Lung cancer is the leading cause of the global cancer incidence and mortality. It is important to obtain an accurate diagnosis of lymph-node metastasis before surgery to select the therapeutic strategy for non-small cell lung cancer (NSCLC) patients. Carbonic anhydrase 9 (CA9) is considered a marker of hypoxia and it has reported that CA9 is associated with tumor invasion and metastasis. In this study, the correlation between the CA9 expression for lymph-node metastases in NSCLC and [18F]FDG PET/CT results was investigated in order to clarify the efficacy of [18F]FDG PET/CT for detecting lymph-node metastases of NSCLC patients. Methods Among the 564 patients who underwent surgical treatment for NSCLC between 2010 and 2016 at our hospital, a total of 338 patients who underwent preoperative [18F]FDG PET/CT were included in this study. CA9 expression was evaluated by immunochemistry. A lymph node with maximum standardized uptake value (SUVmax) ≥2.5 on [18F]FDG PET/CT was preoperatively defined as a metastatic lymph node. Result CA9 positivity was detected in 122 patients; the other 216 patients were CA9-negative. The CA9-positive NSCLC cases significantly associated with pleural invasion (p = 0.0063), pT-factor (p = 0.0080), pN-factor (p = 0.036) and pStage (p = 0.043). CA9-positive patients presented significantly poorer survival rate for OS than that of the CA9-negative patients (p = 0.0024). In the multivariable analysis, histological SCC and CA9 positivity were independent poor-prognosis factors for OS. For the total patient population, the sensitivity and specificity of [18F]FDG PET/CT for lymph-node metastases were 54% and 89%, respectively. In contrast, the sensitivity and specificity were particularly low in the CA9-positive SCC cases (36% and 69%, respectively). Conclusion [18F]FDG PET/CT might not be useful for diagnosing lymph-node metastases of CA9-positive SCC cases of NSCLC.