Pancreatic cancer currently has no subtypes that inform clinical decisions;hence,there exists an opportunity to rearrange the morphological and molecular taxonomy that guides a better understanding of tumor characteri...Pancreatic cancer currently has no subtypes that inform clinical decisions;hence,there exists an opportunity to rearrange the morphological and molecular taxonomy that guides a better understanding of tumor characteristics.Nonetheless,accumulating studies to date have revealed the large-duct type variant,a unique subtype of pancreatic ductal adenocarcinoma(PDA)with cystic features.This subtype often radiographically mimics intraductal papillary mucinous neoplasms(IPMNs)and involves multiple small cysts occasionally associated with solid masses.The“bunch-of-grapes”sign,an imaging characteristic of IPMNs,is absent in large-duct PDA.Large-duct PDA defines the mucin profile,and genetic alterations are useful in distinguishing large-duct PDA from IPMNs.Histologically,neoplastic ducts measure over 0.5 mm,forming large ductal elements.Similar to classic PDAs,this subtype is frequently accompanied by perineural invasion and abundant desmoplastic reactions,and KRAS mutations in codon 12 are nearly ubiquitous.Despite such morphological similarities with IPMNs,the prognosis of large-duct PDA is equivalent to that of classic PDA.Differential diagnosis is therefore essential.展开更多
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 biom...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.展开更多
基金Japan Society for the Promotion of Science(JSPS)KAKENHI,No.19K17480(to Sato H),and No.20H03655(Mizukami Y).
文摘Pancreatic cancer currently has no subtypes that inform clinical decisions;hence,there exists an opportunity to rearrange the morphological and molecular taxonomy that guides a better understanding of tumor characteristics.Nonetheless,accumulating studies to date have revealed the large-duct type variant,a unique subtype of pancreatic ductal adenocarcinoma(PDA)with cystic features.This subtype often radiographically mimics intraductal papillary mucinous neoplasms(IPMNs)and involves multiple small cysts occasionally associated with solid masses.The“bunch-of-grapes”sign,an imaging characteristic of IPMNs,is absent in large-duct PDA.Large-duct PDA defines the mucin profile,and genetic alterations are useful in distinguishing large-duct PDA from IPMNs.Histologically,neoplastic ducts measure over 0.5 mm,forming large ductal elements.Similar to classic PDAs,this subtype is frequently accompanied by perineural invasion and abundant desmoplastic reactions,and KRAS mutations in codon 12 are nearly ubiquitous.Despite such morphological similarities with IPMNs,the prognosis of large-duct PDA is equivalent to that of classic PDA.Differential diagnosis is therefore essential.
基金supported by the National Natural Science Foundation of China(Grants No.81872008,82072702)Shanxi Provincial Grant of Scientific and Technological Innovation Team(Grant No.2022-TD-43)+1 种基金Youth Innovation Team Project of Xi’an Jiaotong University(Grant No.2022-TD-007)Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University,China(Grant No.XJTU1AF-CRF-2019–005).
文摘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.