Association Between Kita-Kyushu Lung Cancer Antigen-1 Positivity and Pathological High-grade Lung Adenocarcinoma

Background/Aim: Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1) is a cancer-testis antigen that represents a promising target for treatment with T-cell receptor (TCR) gene-engineered T cells. This study aimed to evaluate the utility of immunohistochemical detection of KK-LC-1 in resected lung adenocarcinoma specimens. Patients and Methods: We reviewed the medical records of 110 patients who underwent curative resection for lung adenocarcinoma. The original monoclonal antibody against KK-LC-1, Kmab34B3, was evaluated in this study. Overall survival (OS) and recurrence-free survival (RFS) were compared based on KK-LC-1 positivity and epidermal growth factor receptor (EGFR) mutation. Cox regression analyses were performed to identify prognostic factors. Results: Thirty-nine patients (35%) were positive for KK-LC-1. KK-LC-1 positivity was significantly associated with larger invasive tumor size, advanced pathological stage, lymphatic invasion, vascular invasion, and lymph node metastasis. No significant difference in OS was observed between KK-LC-1-positive and -negative patients (5-year OS: 79.8% vs. 94.0%, p=0.07). However, KK-LC-1-positive patients had significantly poorer RFS than KK-LC-1-negative patients (5-year RFS: 67.7% vs. 85.5%, p=0.020). In multivariate analysis, KK-LC-1 positivity was not an independent predictor of RFS (hazard ratio=1.230, p=0.63). EGFR mutation analysis was available for 89 patients, of whom 45 (50.5%) harbored EGFR mutations. In the EGFR mutation-positive subgroup, KK-LC-1-positive patients had significantly poorer OS than KK-LC-1-negative patients (5-year OS: 77.0% vs. 100%, p=0.026). RFS also tended to be poorer in KK-LC-1-positive patients, although the difference did not reach statistical significance (5-year RFS: 66.6% vs. 88.4%, p=0.055). Conclusion: KK-LC-1 positivity was significantly associated with pathological high-grade tumors and poor RFS in patients with lung adenocarcinoma. Moreover, KK-LC-1 may serve as a prognostic factor for lung adenocarcinoma, and KK-LC-1-positive patients may be suitable candidates for TCR reconstitution therapy.