西野 宏

BACKGROUND/AIM: The Hippo signaling pathway comprises mammalian sterile 20-like kinase 1/2, large tumor suppressor 1/2, and Yes-associated protein 1 (YAP1). This study investigated phosphorylated YAP (pYAP, Ser 127) protein expression in oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: Tissues from patients with oral epithelial dysplasia (OED, n=7), carcinoma in situ (CIS, n=14), and OSCC (n=109) were analyzed. RESULTS: Cytoplasmic expression of pYAP was low in OED, CIS, and OSCC tissues. The expression of pYAP was correlated with differentiation, and the expression of low levels of YAP was significantly more common in well-differentiated to moderately differentiated OSCC than in poorly differentiated OSCC. High pYAP expression correlates with characteristics of epithelial-to-mesenchymal transition (EMT), e.g., loss of E-cadherin and increased expression of vimentin and laminin 5 (p<0.0001). Additionally, the protein arginine methyltransferase 1, a positive modulatory factor of YAP activity, was found to be correlated with elevated levels of pYAP expression (p<0.0007). CONCLUSION: The presence of elevated pYAP expression may serve as a prognostic indicator of an aggressive OSCC with EMT during the invasive stage.

BACKGROUND: BRAF V600E mutation is a significant therapeutic target for thyroid cancer, including anaplastic thyroid cancer (ATC). Although targeted therapy for this mutation requires genomic testing in Japan, turnaround time (TAT) is often unacceptably long, especially for certain conditions, such as ATC, which is one of the most aggressive cancers. Here, we evaluated concordance between immunohistochemistry (IHC) with a relatively short TAT of a few days and genomic testing in thyroid cancer. METHODS: Immunohistochemical staining was performed with BRAF (VE1) antibody (Ventana) using the OptiView method on samples already undergoing genomic testing. A pathologist blindly annotated each staining expression with a cut-off of 1% in the cytoplasm. We then calculated the positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement (OPA). RESULTS: We identified 62 samples, including 12 of ATC, that underwent genomic testing using different methods: Oncomine Dx Target Test (ODxTT) (n = 32), MEBGEN BRAF 3 Kit (MEBGEN3) (n = 14), FoundationOne CDx (F1CDx) (n = 13), and GenMineTOP (TOP) (n = 1). Annotation results of IHC were positive for 31, negative for 29, and undeterminable for 2 samples due to low tumor content. PPA, NPA, and OPA were 100%, 91.7%, 96.9% for ODxTT; 100%, 100%, 100% for MEBGEN3; 100%, 80.0%, 93.9% for F1CDx; and incalculable, 100%, 100% for TOP, respectively. Discordance was found in the two undeterminable samples only. CONCLUSION: Concordance between IHC and genomic testing in assessing BRAF V600E was encouragingly high; its reliability and potentially short TAT should benefit patients, especially those with ATC.