Kita-Kyushu lung cancer antigen-1 expression in initial gastric tumors predicts multiple cancer development: A pilot study

BACKGROUND: We have previously reported that the cancer/testis antigen Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is frequently expressed in gastric cancer (GC), with a particularly high positivity rate observed in patients with multiple GCs. Thus, we conducted a preliminary study to further investigate the relationship between KK-LC-1 expression and multiple GCs. Specifically, we aimed to explore the potential clinical utility of KK-LC-1 as a biomarker for identifying patients at risk of developing multiple gastric cancers, with a focus on its expression in the initial tumor lesions. AIM: To investigate the association between KK-LC-1 expression and the development of multiple GCs in a preliminary cohort. METHODS: Among 124 patients (177 lesions) treated for GC at Toho University Medical Center Ohashi Hospital between September 2020 and November 2023, 109 (single cancer: 82; multiple cancers: 27) with available initial tumor specimens were enrolled. KK-LC-1 expression was assessed using immunohistochemistry, and clinicopathological correlations were analyzed using Fisher's exact test. Tumor locations were classified anatomically and analyses were performed, focusing on the initial cancer sites. RESULTS: In tumors located in the upper stomach, KK-LC-1 expression did not correlate with clinicopathological features. However, in the middle and lower stomach, KK-LC-1 expression was significantly associated with older age, differentiated histological types, and multiple cancers. Notably, all patients with multiple GCs had KK-LC-1-positive tumors (100%) in their initial lesions. The KK-LC-1 positivity rate in the initial tumors of multiple cancers in the middle and lower region was significantly higher than that in solitary cancers. Conversely, the absence of KK-LC-1 expression in a solitary tumor located in the middle and lower region may suggest a reduced risk for the subsequent development of multiple primary cancers. CONCLUSION: KK-LC-1 expression in the initial gastric tumors, particularly in the middle and lower stomach regions, may serve as a predictive biomarker for the future development of multiple GCs.