Purpose To explore the clinicopathological characteristics of tonsil squamous cell carcinoma(TSCC),and to explore the whole exome mutations and tumor mutational bur-den(TMB)in TSCC cases.Methods Ten patients with clini-cally and histopathologically confirmed TSCC and their clinico-pathological characteristics were collected,The expression of CK(AE1/AE3),CK5/6,p63,p40,p16 and Ki67 were meas-ured by two steps of EnVision,and the whole exome sequencing(WES)and TMB were conducted in 3 of them.Results A-mong the 10 patients,there were 6 females and 4 males which aged from 43 to 76 years old.Microscopically,the cancer cells infiltrated into the subdermis of crypts in the form ofnests and irregular cord,accompanied by comedo like necrosis,intercellu-lar bridges,and varying degrees of keratinization.Obvious atyp-ia and mitotic figures were easily seen.Follow-up was available in all cases,ranging from 6 to 45 months.Nine cases had sur-vived.Immunohistochemistry staining showed that all cases were positive for CK(AE1/AE3),CK5/6,p63,p40,and p16 was positively expressed in three cases,and the proliferation index Ki67 ranged from 40％to 90％.The WES of three cases showed that ARID1B and LRP6 were common cancer susceptibility genes,and WDFY4,ZFHX4 exhibited higher mutation rates,which were both 3/3.The TMB analysis showed that one out of three cases was＞9 mut/Mb.Conclusion The early symptoms of TSCC are not obvious that lead to easily missed and misdiag-nosed.The WES analyses suggest that WDFY4 and ZFHX4 had a higher mutation rate.The TMB analysis suggests that some TSCC patients may benefit from immunotherapy.

Renal cell carcinoma (RCC) is one of the most aggressive malignancies in the genitourinary system with a poor prognosis, especially in patients with RCC who have metastases. RCC is conventionally considered not sensitive to radiotherapy. Compared with conventional radiotherapy, stereotactic body radiotherapy (SBRT) has the characteristics of higher precision, higher irradiation dose, and less damage to the surrounding tissue. In recent years, SBRT has shown definite efficacy in the treatment of primary and advanced metastatic RCC. SBRT combined with targeted therapy and immunotherapy can improve the local tumor control rate and cause fewer adverse reactions in patients with primary and advanced metastatic RCC. This article reviews the literature on the strategy and progress of SBRT in combination with targeted therapy and immunotherapy.

Objective:To investigate the clinicopathological features, immunohistochemical phenotypes and molecular characteristics of adenosquamous carcinoma of the lung(ASC)in elderly patients.Methods:Clinical data of 72 ASC patients in the Department of Pathology, The Second Affiliated Hospital of Soochow University from January 2009 to December 2020 were retrospectively analyzed, and 48 patients aged ≥60 years were selected.Clinical manifestations, imaging findings, histopathological and immunohistochemical characteristics were collected, and gene mutations were detected by the amplification refractory mutation system(ARMS-PCR).Results:There were 48 patients including 32 males and 16 females with a mean age of 70 years(range: 60-84 years). The maximum diameters of the tumors ranged from 0.3 to 9.0 cm(mean: 2.8 cm). Microscopically, the tumors contained two components, squamous cell carcinoma and adenocarcinoma, with the squamous cell carcinoma tissue showing intercellular bridges and the adenocarcinoma tissue showing papillary, acinar or tubular structures.Immunohistochemistry assays detected varying expression levels of CK7(30/31), CK5/6(20/28), TTF1(12/31), P40(15/17), and P63(12/13). Molecular testing showed that the EGFR mutation rate was 58.8%(10/17)and the ALK fusion mutation rate was 5.9%(1/17), while ROS1 and MET mutations were not detected.All 48 patients underwent surgical resection.Conclusions:ASC cases are relatively rare and prone to misdiagnosis.The diagnosis requires the combination of HE morphology, immunohistochemistry and imaging examination, and surgery is the main treatment option.The mutation rate of the EGFR gene is relatively high in ASC patients.

Objective:To explore the clinicopathological and genetic characteristics of sporadic medullary thyroid carcinoma (MTC) and new therapeutic targets for sporadic MTC.Methods:Based on family and personal disease history, we identified 32 sporadic MTC who underwent surgical resection from Jan 2010 to Dec 2022. Clinicopathological and immunohistochemical features were analyzed in all patients, while 6 of them were subject to the whole exome sequencing (WES).Results:Compared with those of low-grade sporadic MTC, patients with high-grade tumors were more likely to have lymph node metastasis at presentation ( χ2=4.428, P=0.040); less likely to be cured by biochemical treatment ( χ2=4.072, P=0.044). Pathological grading scheme, biochemical cure, and TNM stage were independent risk factors of disease free survival. WES was performed on 6 pairs of normal tissues. We screened RET and RAS as driver mutations, and the mutation ratio was 3/6 respectively. Patients with RET or RAS mutations had no recurrence. In addition, we detected PDGFRA somatic mutation, with a mutation ratio of 1/6. Conclusions:For sporadic MTC cases, the pathological grading system has important prognostic value, and RET and RAS somatic mutations are the main driver mutations. PDGFRA are potential therapeutic targets for sporadic MTC.

OBJECTIVE To investigate the inhibitory effect of berberine （BER） on the invasion and migration of human renal carcinoma cells and its potential mechanism. METHODS Using human renal carcinoma OSRC-2 cell as object， alamarBlue assay was adopted to detect the inhibitory effects of 0 （control group）， 25， 50， 75， 100， 125， 150， 175 and 200 μmol/L BER on the proliferation of OSRC-2 cell after treatment for 24 h and 48 h. After treated with 0（control group）， 50， 100 μmol/L BER for 48 h， the effect of BER on cell cycle was analyzed by flow cytometry. The migration of OSRC-2 cells in 24 h and 36 h was observed by cell scratch test， and the invasion ability of OSRC-2 cells in 24 h was detected by Transwell assay. The protein expression of methyltransferase-like 3 （METTL3） was detected by Western blot after treatment for 48 h， and RNA methylation quantification kit was used to detect the levels of N6-methyladenosine （m6A） in OSRC-2 cells. RESULTS Compared with control group， BER at different concentrations could significantly decrease the survival rate of OSRC-2 cells （P＜0.01）， and showed a dose-dependent and time-dependent manner. After 48 h of BER treatment at 50， 100 μmol/L， the cell was arrested in G0/G1 phase （P＜0.01）. Compared with control group， the migration and invasion abilities of cells in 50， 100 μmol/L BER group were significantly decreased （P＜0.05 or P＜0.01）； the protein expression of METTL3 and the level of m6A in RNA were significantly decreased （P＜0.01）. CONCLUSIONS BER can inhibit level of m6A by down-regulating the expression of METTL3， thereby inhibiting the invasion and metastasis of human renal carcinoma cells.