Publication

Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2)

Journal Paper/Review - Aug 27, 2015

Units
PubMed
Doi
Contact

Citation
Feilchenfeldt J, Jochum W, Shoji H, Kushima R, Wagner D, Shimada Y, Cats A, Knuth A, Moch H, Aebi S, Diebold J, Khanfir K, Varga Z, Siano M, Grabsch H, Held U, Schuknecht B, Trip A, Hamaguchi T, Gut P, Balague O, Hofer S. Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2). Br J Cancer 2015; 113:716-21.
Type
Journal Paper/Review (English)
Journal
Br J Cancer 2015; 113
Publication Date
Aug 27, 2015
Issn Electronic
1532-1827
Pages
716-21
Brief description/objective

BACKGROUND
Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown.

PATIENTS AND METHODS
A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively. Inclusion in the study required a predefined clinical data set, a central neuro-radiological or histopathological confirmation of metastatic CNS involvement and central assessment of HER2 by immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition, expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by IHC.

RESULTS
One hundred patients fulfilled the inclusion criteria. The population's median age was 59 years (interquartile range: 54-68), of which 85 (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin. HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from initial diagnosis to the development of brain metastases (BMets) or leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss of expression in at least one DNA MMR proteins in 6%.

CONCLUSIONS
The proportion of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and CNS involvement was higher than expected. The impact of anti-HER2 therapies should be studied prospectively.