Preoperative levels of folate receptor-positive circulating tumor cells in different subtypes of early-stage lung adenocarcinoma: Predictive value for determining extent of surgical resection

BACKGROUND: The objective was to measure the correlations of preoperative levels of folate receptor-positive circulating tumor cells (FR(+)CTCs) with clinical characteristics and histologic subtype in early-stage lung adenocarcinoma, and to determine the predictive value of FR(+)CTC level in preoperative determination of the extent of surgical resection. PATIENTS AND METHODS: In this retrospective, single-institution, observational study, preoperative FR(+)CTC levels were measured via ligand-targeted enzyme-linked polymerization in patients with early-stage lung adenocarcinoma. Receiver operating characteristic (ROC) analysis was used to identify the optimal cutoff value of FR(+)CTC level for prediction of various clinical characteristics and histologic subtypes. RESULTS: No significant difference in FR(+)CTC level was observed among patients with adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) (P = 0.813). Within the non-mucinous adenocarcinoma group, no difference was observed among patients with tumors whose predominant growth patterns were lepidic, acinar, papillary, micropapillary, solid, and complex gland (P = 0.053). However, significant differences in FR(+)CTC level were observed between patients with and without the micropapillary subtype [11.21 (8.22-13.61) vs. 9.85 (7.43-12.63), P = 0.017], between those with and without the solid subtype [12.16 (8.27-14.90) vs. 9.87 (7.50-12.49), P = 0.022], and between those with any of the advanced subtypes (micropapillary, solid, or complex glands) vs. none of these [10.48 (7.83-13.67) vs. 9.76 (7.42-12.42), P = 0.032]. FR(+)CTC level was also correlated with degree of differentiation of lung adenocarcinoma (P = 0.033), presence of visceral pleural invasion (VPI) of lung carcinoma (P = 0.003), and lymph node metastasis of lung carcinoma (P = 0.035). CONCLUSION: FR(+)CTC level is of potential predictive value in determining the presence of aggressive histologic patterns (micropapillary, solid, and advanced subtypes), degree of differentiation, and occurrence of VPI and lymph node metastasis in IAC. Measurement of FR(+)CTC level combined with intraoperative frozen sections may represent a more effective method of guiding resection strategy in cases of cT1N0M0 IAC with high-risk factors.