Keratin 1 and keratin 18 as immunohistochemical markers for distinguishing pulmonary metastases of oral squamous cell carcinoma from primary lung squamous cell carcinoma.

Accurate distinction between pulmonary metastases of oral squamous cell carcinoma (OSCC) and primary lung squamous cell carcinoma (LSCC) is critical for clinical management, but practical immunohistochemical markers remain limited in routine practice. We screened three public mRNA expression datasets, GSE84846 for OSCC and The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium for LSCC, and selected six candidate markers for immunohistochemical evaluation in 39 OSCC and 92 LSCC specimens. Among them, keratin 1 (K1; encoded by KRT1) and keratin 18 (K18; encoded by KRT18) showed the most significant differential expression between OSCC and LSCC (both p < 0.0001). K1 was predominantly expressed in OSCC and rarely in LSCC, whereas K18 showed the opposite pattern. K1 showed high specificity (0.989) and an odds ratio of 117.8, while K18 showed a specificity of 0.974 and an odds ratio of 59.1. Receiver operating characteristic analysis confirmed strong discriminatory performance for K1 (AUC, 0.865) and K18 (AUC, 0.872). In four whole-exome sequencing-confirmed pairs of primary OSCC and lung metastases, staining patterns for both markers were concordant between the primary oral tumors and pulmonary lesions. These findings support K1 and K18 as practical markers for distinguishing pulmonary metastases of OSCC from primary LSCC.