Epidermal growth factor receptor signaling pathway is frequently altered in ampullary carcinoma at protein and genetic levels

Mikhitarian, Kaidi; Pollen, Maressa; Zhao, Zhiguo; Shyr, Yu; Merchant, Nipun B.; Parikh, Alexander A.; Revetta, Frank; Washington, Mary Kay; Shi, Chanjuan

doi:10.1038/modpathol.2013.185

Cited by 33 publications

(37 citation statements)

References 56 publications

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“… 25 Moreover, several studies showed discrepant results regarding the prognostic role of KRAS mutation for RFS or OS. 13 , 14 , 26 – 30 In one of them, whereas KRAS mutation was not associated with prognosis, patients with specific KRAS G12D mutation had a shorter survival compared to KRAS non-G12D mutation patients and KRAS -wild type patients. 29 Furthermore, KRAS mutation appears as an early event in AA pathogenesis, as it has been reported present in 20% of adenomas and 80% of AA in a series of endoscopic papillectomy samples.…”

Section: Discussionmentioning

confidence: 98%

Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study

et al. 2019

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BACKGROUND: Ampullary adenocarcinoma (AA) originates from either intestinal (INT) or pancreaticobiliary (PB) epithelium. Different prognostic factors of recurrence have been identified in previous studies. METHODS: In 91 AA patients of the AGEO retrospective multicentre cohort, we evaluated the centrally reviewed morphological classification, panel markers of Ang et al. including CK7, CK20, MUC1, MUC2 and CDX2, the 50-gene panel mutational analysis, and the clinicopathological AGEO prognostic score. RESULTS: Forty-three (47%) of the 91 tumours were Ang-INT, 29 (32%) were Ang-PB, 18 (20%) were ambiguous (Ang-AMB) and one could not be classified. Among these 90 tumours, 68.7% of INT tumours were Ang-INT and 78.2% of PB tumours were Ang-PB. MUC5AC expression was detected in 32.5% of the 86 evaluable cases. Among 71 tumours, KRAS, TP53, APC and PIK3CA were the most frequently mutated genes. The KRAS mutation was significantly more frequent in the PB subtype. In multivariate analysis, only AGEO prognostic score and tumour subtype were associated with relapse-free survival. Only AGEO prognostic score was associated with overall survival. CONCLUSIONS: Mutational analysis and MUC5AC expression provide no additional value in the prognostic evaluation of AA patients. Ang et al. classification and the AGEO prognostic score were confirmed as a strong prognosticator for disease recurrence. BACKGROUNDAmpullary adenocarcinomas (AA) are rare malignant neoplasms arising from the ampulla of Vater, a dilated conduit resulting from the union of intestinal and pancreatobiliary epithelia. Histologically, AA are heterogeneous and are classified into five subgroups: the intestinal (INT) subtype; the pancreatobiliary (PB) subtype; the mixed subtype; the mucinous subtype, and the poorly differentiated subtype. 1 Patient outcome appears to be influenced by histopathological subtype, with the INT subtype being associated with a good prognosis in most studies. 2,3 Moreover, this classification could help to tailor appropriately the chemotherapy regimen using fluoropyrimidine-based regimens for INT subtype tumours and gemcitabine-based regimens for PB subtype tumours. On the other hand, a retrospective AGEO (Association des Gastro-Entérologues Oncologues) study determined a prognostic score based on age, general condition, tumour differentiation and TNM stage which was independent of the histopathological subtype. 4 Recently, immunohistochemistry (IHC)-based classification of AA has been proposed to establish INT versus PB lineage in order www.nature.com/bjc

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Section: Discussionmentioning

confidence: 98%

Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study

et al. 2019

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“…The 24 pancreatobiliary subtype cancers had a 42% incidence of K-ras mutation ( Table 2). 48 Studies that analyzed both pancreatic and ampullary cancers for K-ras mutation reported that the overall incidence of K-ras mutation in their series was lower than that in reported in PCs. These lower figures were initially thought to reflect a lower incidence of K-ras mutation in PC, but the APGI genome study has confirmed the high incidence of K-ras mutation in PC.…”

Section: Genetic and Molecular Aberrations In Ampullary Cancer Subtypementioning

confidence: 90%

“…Unlike PC, ampullary cancers have a far lower incidence of K-ras mutation. The incidence of K-ras mutation in ampullary cancer was analyzed by Mikhitarian et al 48 Of 52 cancers, 25 were intestinal subtype with a 52% incidence of K-ras mutation. The 24 pancreatobiliary subtype cancers had a 42% incidence of K-ras mutation ( Table 2).…”

Section: Genetic and Molecular Aberrations In Ampullary Cancer Subtypementioning

confidence: 99%

Advances in Molecular Pathology and Treatment of Periampullary Cancers

Chandrasegaram¹,

Chen

Price

et al. 2016

Pancreas

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“…Other EGFR active drugs have not led to a prolonged OS, when added to standard chemotherapy [ 7 ]. EGFR expression has also been shown to be more common in PB-type than in I-type ampullary adenocarcinoma [ 14 ] and overexpression has been associated with shorter OS in I-type but not in PB-type tumours [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1, 2 and 3 in Periampullary Adenocarcinoma

et al. 2016

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Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous group of tumours with dismal prognosis, for which there is an urgent need to identify novel treatment strategies. The human epithelial growth factor receptors EGFR, HER2 and HER3 have been studied in several tumour types, and HER-targeting drugs have a beneficial effect on survival in selected types of cancer. However, these effects have not been evident in pancreatic cancer, and remain unexplored in other types of periampullary cancer. The prognostic impact of HER-expression in these cancers also remains unclear. The aim of this study was therefore to examine the expression and prognostic value of EGFR, HER2 and HER3 in periampullary cancer, with particular reference to histological subtype. To this end, protein expression of EGFR, HER2 and HER3, and HER2 gene amplification was assessed by immunohistochemistry and silver in situ hybridization, respectively, on tissue microarrays with tumours from 175 periampullary adenocarcinomas, with follow-up data on recurrence-free survival (RFS) and overall survival (OS) for up to 5 years. EGFR expression was similar in pancreatobiliary (PB) and intestinal (I) type tumours, but high HER2 and HER3 expression was significantly more common in I-type tumours. In PB-type cases receiving adjuvant gemcitabine, but not in untreated cases, high EGFR expression was significantly associated with a shorter OS and RFS, with a significant treatment interaction in relation to OS (pinteraction = 0.042). In I-type cases, high EGFR expression was associated with a shorter OS and RFS in univariable, but not in multivariable, analysis. High HER3 expression was associated with a prolonged RFS in univariable, but not in multivariable, analysis. Neither HER2 protein expression nor gene amplification was prognostic. The finding of a potential interaction between the expression of EGFR and response to adjuvant chemotherapy in PB-type tumours needs validation, and merits further study.

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Epidermal growth factor receptor signaling pathway is frequently altered in ampullary carcinoma at protein and genetic levels

Cited by 33 publications

References 56 publications

Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study

Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study

Advances in Molecular Pathology and Treatment of Periampullary Cancers

Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1, 2 and 3 in Periampullary Adenocarcinoma

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