TP53 mutation + PD-L1 expression

Results The 64 patients with colorectal cancer were at a male-to-female ratio of 1.21∶1,with the mean age of (56.59±13.27) years.The tumors were located in the colon in 46(71.88%) patients and in the rectum in 18(28.12%) patients.Sixty(93.75%) patients presented adenocarcinoma,and 4(6.25%) patients presented other types of tumors.The patients in T1/T2 and T3/T4 phases accounted for 17.19%(n=11) and 82.81%(n=53),respectively.Lymph node metastasis occurred in 24(37.50%) patients.The immunohistochemical staining results showed partially down-regulated or absent expression of SMARCA4 in 1(1.56%) patient,positive BRAF expression in 4(6.25%) patients,and mutant expression of P53 in 35(54.69%) patients.The PD-1-expressing tumor associated immune cell was proportion score<10% in 45(70.31%) patients and≥10% in 19(29.69%) patients.The PD-L1 combined positive score was<10 in 52(81.25%) patients and≥10 in 12(18.75%) patients.The gene fusion of NTRK1,NTRK2,and NTRK3 was negative in all the patients,and BRAF V600E gene mutation was positive in 4(6.25%) patients.The SMARCA4 gene alteration was not detected in the patient with partial expression missing of SMARCA4.The PD-L1 combine positive score was correlated with the deficient mismatch repair(dMMR)/microsatellite instability-high (MSI-H) and the PD-1 expression (χ2=10.223,P=0.001;χ2=11.979,P=0.001). Conclusions The down-regulated or absent SMARCA4 expression and NTRK gene fusion are rare in the patients with colorectal cancer in Tibet.A few patients present BRAF V600E gene mutations,and Pan-TRK and BRAF expression can be used for the primary screening of NTRK gene fusion and BRAF gene mutation.The patients with dMMR/MSI-H are prone to high expression of PD-L1 and expected to benefit from immunotherapy.No significant correlation exists between P53 mutation and PD-L1 expression.The high expression of PD-1 is positively correlated with the high expression of PD-L1.

Although 60% of patients can be cured by standard R-CHOP (rituximab plus cyclophosphamide, doxoru bicin, vincristine, and prednisone) as frontline therapy, patients with resistance to primary chemoimmunotherapy have a poor prognosis...Afterwards, patients with TP53 mutations and PD-L1 expression (≥30% by IHC) are randomly assigned (1:1) to receive either sintilimab plus R-CHOP regimen (group A) or R-CHOP only (group B) for 5 cycles, until disease progression, unacceptable toxicity or withdrawal of consent...Safety was assessed in all treated patients. The study is registered with www.chictr.org, NCT05280626 and is ongoing.

Metastatic lung cancer patients with discoverable mutations on NGS are more likely to have metastatic disease to the brain. PDL-1 expression and TP53 mutation tend to lead to disease metastatic to organs other than brain or bone. Patients with EGFR mutations, despite having a great propensity to brain metastasis, have significantly better PFS and OS than patients with KRAS/NRAS and TP53 mutations, likely due to targeted therapy options.

TP53 mutations could represent a potential biomarker for treatment selection for pts with low PDL1 expression treated with chemo-immunotherapy. Prospective validation is needed.