Loss of chromosome 9p21 is associated with a poor prognosis in adenosquamous carcinoma of the pancreas

Adenosquamous carcinoma of the pancreas(ASCP)is a rare histological subtype of pancreatic cancer with a poor prognosis and a high metastasis rate.However,little is known about its genomic landscape and prognostic biomarkers.A total of 48 ASCP specimens and 98 pancreatic ductal adenocarcinoma(PDAC)tumour specimens were sequenced to explore the genomic landscape and prognostic biomarkers.The homozygous deletion of the 9p21.3 region(including CDKN2A,CDKN2B,and MTAP)(9p21 loss)occurred in both ASCP and PDAC,and a higher frequency of 9p21 loss was observed in ASCP(12.5%vs 2.0%,P=0.022).Notably,9p21 loss was significantly associated with poor disease-free survival(DFS)in ASCP patients(mDFS(Median DFS)=4.17 vs 7.33 months,HR(Hazard Ratio)=3.70,P=0.009).The most common gene alterations in patients with ASCP were KRAS(96%),TP53(81%),CDKN2A(42%),SMAD4(21%),CDKN2B(13%),and FAT3(13%).The mutation rates of ACVR2A(6.25%vs 0%),FANCA(6.25%vs 0%),RBM10(6.25%vs 0%),and SPTA1(8.33%vs 1.02%)were significantly higher in ASCP than in PDAC.In conclusion,we have comprehensively described the genomic landscape of the largest cohort of ASCP patients to date and highlight that 9p21 loss may be a promising prognostic biomarker for ASCP,which provides a molecular basis for prognosis prediction and new therapeutic strategies for ASCP.

The value of the lymph node ratio and total number of lymph nodes examined for resected pancreatic signet ring cell carcinoma:a retrospective cohort study

Background:Pancreatic signet ring cell carcinoma(SRCC)is an exceedingly rare histological subtype of pancreatic cancer.Previous studies have focused on the trends of incidence and independent predictors of pancreatic SRCC.Our objectives of the study were to analyze the prognostic value of the lymph node ratio(LNR)and to explore the minimal number of lymph nodes examined to accurately evaluate the N stage in resected pancreatic SRCC.Method:We analyzed 120 patients diagnosed from January 1,1990,to December 31,2016,constituted the study cohort from the Surveillance,Epidemiology,and End Results(SEER)registry.We calculated the overall survival(OS)of these patients by using a Kaplan–Meier analysis.The Kaplan–Meier analysis was used to analyze the influence of various factors on the prognosis of patients in the univariate analysis.The multivariate Cox analysis were applied to find independent prognostic factors of patients with pancreatic SRCC.Receiver-operating characteristic curve(ROC)analysis to investigate the discriminatory ability of the total number of lymph nodes examined(TNLE)relative to whether lymph node metastasis was present.Results:The median number of lymph nodes examined among 120 patients with resected pancreatic SRCC was 14(interquartile range:6.25–20.0).According to the univariate analysis of OS,age,grade,chemotherapy,LNR,and TNLE were significantly different(P<.05).We demonstrated the prognostic benefit of chemotherapy in resected pancreatic SRCC,whereas radiotherapy was not associated with improved survival.The multivariate survival analysis showed that LNR and grade were independent prognostic indicators after pancreatic SRCC resection for OS.TNLE≥8 showed the highest discriminatory power for evaluating lymph node metastasis(Area under curve(AUC):0.656,95%confidence interval:0.564–0.741,Youden index:0.2533,sensitivity:78.67%,specificity:46.67%,P=.003).Conclusion:Our study indicated that the LNR was a valuable independent prognostic factor for resected pancreatic SRCC.Regional lymphadenectomy of at least 8 lymph nodes was necessary to accurately stage patients.An adequate number of lymph nodes examined are necessary for clinicians to accurately predict the significance of the LNR in resected pancreatic SRCC.