Oral diseases · 2024
The genetic and immune features of salivary gland secretory carcinoma with high-grade transformation.
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Wang Yu, Sun Jingjing, Sun Bao, Zhang Chunye, Tian Zhen, Wang Lizhen, Li Jiang
Аннотация
OBJECTIVES: To compare the clinicopathological, molecular, and immune features of conventional and high-grade transformation (HGT) secretory carcinoma (SC) in salivary glands.
MATERIALS AND METHODS: The clinicopathological data of 88 cases including 74 conventional SCs and 14 SCs with HGT were reviewed. Targeted next-generation sequencing was performed in 11 SCs with HGT and 7 conventional SCs. The level of PD-L1 and CD8+ TILs was determined by immunohistochemistry.
RESULTS: Compared with the conventional group, the rates of nodal metastasis, local recurrence, distant metastasis and mortality were significantly higher in the HGT cohort. Mutations of ARID1A/B, KMT2A, HOXD13, NRG1 and ETV6 genes were identified in HGT SCs. A recurrent E307G mutation in GATA6 gene was also observed in two cases. Two deceased HGT patients with distant metastasis harboured NOTCH3 mutations. ETV6-RET translocation was prone to occur in the HGT SCs. Additionally, PD-L1 expression was low, and CD8+ TILs were sparse in most HGT cases.
CONCLUSION: Our findings reveal novel gene alterations involved in the progression of HGT in SCs. Most HGT SCs patients cannot benefit from PD-L1 blocking and may be approached with a distinct treatment strategy including the lymph node dissection and application of molecular target drugs in precision oncology.
MATERIALS AND METHODS: The clinicopathological data of 88 cases including 74 conventional SCs and 14 SCs with HGT were reviewed. Targeted next-generation sequencing was performed in 11 SCs with HGT and 7 conventional SCs. The level of PD-L1 and CD8+ TILs was determined by immunohistochemistry.
RESULTS: Compared with the conventional group, the rates of nodal metastasis, local recurrence, distant metastasis and mortality were significantly higher in the HGT cohort. Mutations of ARID1A/B, KMT2A, HOXD13, NRG1 and ETV6 genes were identified in HGT SCs. A recurrent E307G mutation in GATA6 gene was also observed in two cases. Two deceased HGT patients with distant metastasis harboured NOTCH3 mutations. ETV6-RET translocation was prone to occur in the HGT SCs. Additionally, PD-L1 expression was low, and CD8+ TILs were sparse in most HGT cases.
CONCLUSION: Our findings reveal novel gene alterations involved in the progression of HGT in SCs. Most HGT SCs patients cannot benefit from PD-L1 blocking and may be approached with a distinct treatment strategy including the lymph node dissection and application of molecular target drugs in precision oncology.