ERBB2 gene as a potential therapeutic target in small bowel adenocarcinoma

Laforest, A.; Aparicio, Thomas; Zaanan, Aziz; Silva, Fábio Pittella; Didelot, Audrey; Desbeaux, A.; Corre, Delphine Le; Benhaïm, Léonor; Pallier, Karine; Aust, Daniela E.; Pistorius, Steffen; Blons, Hélène; Svrcek, Magali; Laurent‐Puig, Pierre

doi:10.1016/j.ejca.2014.04.007

Cited by 83 publications

(112 citation statements)

References 17 publications

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“…Interestingly, we found a very similar mutational profile between INT AA and our previously published small bowel cancer series, excepting the rarity of the ERBB2 mutation in AA. 24 Regarding the prognostic value of the different gene mutations, none was associated with survival. This finding differs from the results of a recent meta-analysis that reported a significant correlation in AA between the KRAS mutation and a worse RFS, but no correlation with OS.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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

et al. 2019

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“…In addition, genomic profiling identified potentially targetable genetic alterations in most SBC cases (91%) [47]. Laforest and colleagues [55] found ERBB2/HER2 alterations in 12% of spo-SBC, through mutations (7 cases) or amplifications (3 cases). Our group first described HER2 amplification in two CD-SBC and in two CrD-SBC [2].…”

Section: Histopathology and Molecular Biologymentioning

confidence: 99%

“…In particular, in this trial seven patients had a progression of SBC, whereas the remaining two ones showed stable SBC [78]. It has been hypothesized that SBC as well as right-sided colon carcinomas benefit less from anti-epidermal growth factor receptor agents than left-sided colon carcinomas due to their distinct embryologic origin, namely midgut for SBC and right-sided colon carcinomas and hindgut for left-sided colon carcinomas [78,79] Although HER2 amplification is rare in CD-SBC and CrD-SBC [2], it is worth being investigated as a potential therapeutic target of anti-HER2 receptor monoclonal antibody trastuzumab [55,80]. Expression…”

Section: Prognosis and Treatmentmentioning

confidence: 99%

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: the Current Knowledge

Giuffrida¹,

Vanoli²,

Arpa³

et al. 2018

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Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders, including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumor-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC.

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“…The majority of SBA cases had stage IV disease (78.1%), and the majority of samples were from the primary small bowel tumor (60.3%). The most common genomic alterations in SBA were observed in TP53 (58.4%), KRAS (53.6%), APC (26.8%), SMAD4 (17.4%), PIK3CA (16.1%), CDKN2A (14.5%), and ARID1A (12.3%), findings reinforced in the work of Laforest et al [22]. There was no significant difference in rates of genomic alterations between primary and metastatic biopsy sites tested except with BRAF, which was more commonly mutated in metastatic lesions (p 5 .047).…”

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confidence: 59%