Concurrent MET copy number gain and KRAS mutation is a poor prognostic factor in pancreatobiliary subtype ampullary cancers

Kwon, Mi Jung; Kim, Jeong Won; Jeon, Jang Yong; Nam, Eun Sook; Cho, Seong Jin; Park, Hye-Rim; Min, Soo Kee; Seo, Jinwon; Min, Kyueng‐Whan; Choe, Ji Young; Lee, Hye Kyung

doi:10.1016/j.prp.2017.01.004

Cited by 9 publications

(4 citation statements)

References 28 publications

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“…It can be used to predict the outcomes of different AVC patients with mixed subtypes. Additionally, this algorithm was consistent with reports ( 45 , 48 ), indicating that the genomic scores were higher in patients with the pancreaticobiliary subtype (mutations of the KRAS gene) and associated with lower survival probability.…”

Section: Molecular Classification Associated With Clinical Outcomessupporting

confidence: 90%

“…Although there were overlapping genomic alterations between the two histological subtypes, a trend has been observed ( 42 ) that more frequent KRAS mutations are found in AVC patients with the pancreaticobiliary subtype (61%) than in AVC patients with the intestinal subtype (29%). When histological subtypes were analyzed together ( 48 ), concurrent KRAS gene positivity and MET copy number gain were proven to be independent prognostic factors for DFS in AVC patients with the pancreaticobiliary subtype (HR = 4.926, P = 0.047). This may contribute to the findings that KRAS mutation is significantly associated with patients presenting with a large tumor size ( 38 ).…”

Section: Molecular Classification Associated With Clinical Outcomesmentioning

confidence: 99%

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Ampulla of Vater carcinoma: advancement in the relationships between histological subtypes, molecular features, and clinical outcomes

Líu

Zhu

2023

Front. Oncol.

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The incidence of ampulla of Vater carcinoma, a type of periampullary cancer, has been increasing at an annual percentage rate of 0.9%. However, patients with ampulla of Vater carcinoma have quite different prognoses due to the heterogeneities of the tissue origin of this carcinoma. In addition to TNM staging, histological subtypes and molecular features of ampulla of Vater carcinoma are the key factors for predicting the clinical outcomes of patients. Fortunately, with the development of testing technology, information on the histological subtypes and molecular features of ampulla of Vater carcinoma is increasingly being analyzed in-depth. Patients with the pancreaticobiliary subtype have shorter survival times. In immunohistochemical examination, high cutoff values of positive MUC1 staining can be used to accurately predict the outcome of patients. Mutant KRAS, TP53, negative SMAD4 expression, and microsatellite stability are related to poor prognosis, while the clinical value of BRCA1/BRCA2 mutations is limited for prognosis. Testing the histological subtypes and molecular characteristics of ampulla of Vater carcinoma not only is the key to prognosis analysis but also provides extra information for targeted treatment to improve the clinical outcomes of patients.

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Section: Molecular Classification Associated With Clinical Outcomessupporting

confidence: 90%

Section: Molecular Classification Associated With Clinical Outcomesmentioning

confidence: 99%

Ampulla of Vater carcinoma: advancement in the relationships between histological subtypes, molecular features, and clinical outcomes

Líu

Zhu

2023

Front. Oncol.

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“…MET and HGF were expressed in 31.0% and 31.7% of gastric cancers, respectively, where approximately half of which were PD-L1 positive. PD-L1 expression was positively correlated with the overexpression of MET and HGF, which has been associated with adverse histological characteristics in many malignancies [ 13 , 31 - 33 ]. However, only MET positivity, but not HGF, was an independent factor that was upregulated and affected PD-L1 overexpression as shown by a multivariate analysis.…”

Section: Discussionmentioning

confidence: 99%

“…The MET/hepatocyte growth factor (HGF) pathway is a potential candidate, since MET-induced signaling has been reported to induce PD-L1 expression in renal cell cancers [ 12 ]. Binding of HGF to MET induces the phosphorylation of the docking site and stimulates mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways [ 13 ], which are one of the drivers that upregulate PD-L1 expression in melanoma and non-small cell lung cancer [ 6 , 14 ]. In addition, PD-L1 upregulation has been reported in Epstein-Barr virus (EBV)-associated malignancies, including gastric cancers, nasopharyngeal carcinoma, and malignant lymphoma [ 15 - 18 ].…”

Section: Introductionmentioning

confidence: 99%

Programmed death ligand-1 and MET co-expression is a poor prognostic factor in gastric cancers after resection

et al. 2017

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Programmed death-ligand 1 (PD-L1) plays an essential protein for immune evasion, contributing to tumor development and progression. Recent studies have reported MET as an upregulator for PD-L1 overexpression through an oncogenic pathway. However, an association between PD-L1 expression with MET has not been reported in gastric cancer.The prognostic significance of PD-L1 and its association with Epstein-Barr virus (EBV), microsatellite instability (MSI), and mucin phenotype remain controversial.We performed in situ hybridization for EBV-encoded RNA and immunohistochemistry in tissue microarrays for 394 gastric cancers. A multiplex polymerase chain reaction with five quasimonomorphic markers was performed for MSI.PD-L1 expression was observed in 123 cases (31.2%), and clinicopathological features such as MET overexpression, high pT stage, and a lack of lymphatic invasion represent significant risk factors associated with PD-L1 overexpression in gastric cancers. No associations of EBV, MSI, or mucin phenotype with PD-L1 expression were statistically significant. PD-L1 expression was a strong indicator for worse overall survival (OS) but borderline significant in disease-free survival (DFS). A combined analysis of PD-L1 and MET expression indicated that the PD-L1+/MET+ subgroup showed the worst prognosis when compared to the PD-L1-/MET- subgroup, which had the best clinical outcome. Furthermore, PD-L1 overexpression exhibited poor prognosis in terms of both OS and DFS in EBV-negative, microsatellite stable, and intestinal mucin phenotype tumors. In conclusion, this is the first study to evaluate the overexpression of MET as a risk factor for PD-L1 positivity in gastric cancer tissue as well as the reliability and prognostic relevance of PD-L1/MET co-expression after surgery.

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Identification and prevalence of potentially therapeutic targetable variants of major cancer driver genes in ampullary cancer patients in India through deep sequencing

et al. 2021

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Concurrent MET copy number gain and KRAS mutation is a poor prognostic factor in pancreatobiliary subtype ampullary cancers

Cited by 9 publications

References 28 publications

Ampulla of Vater carcinoma: advancement in the relationships between histological subtypes, molecular features, and clinical outcomes

Ampulla of Vater carcinoma: advancement in the relationships between histological subtypes, molecular features, and clinical outcomes

Programmed death ligand-1 and MET co-expression is a poor prognostic factor in gastric cancers after resection

Identification and prevalence of potentially therapeutic targetable variants of major cancer driver genes in ampullary cancer patients in India through deep sequencing

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