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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


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Mentions: Twenty-nine registered patients were excluded because (i) there was no tissue available for confirmation of the diagnosis and further analysis (8), (ii) squamous cell histology (7), (iii) lack of clinical data (11), or (iv) the absence of radiologically or histologically confirmed BMets or LC (3) (Figure 1).


Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2)
Consort diagram.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4559836&req=5

fig1: Consort diagram.
Mentions: Twenty-nine registered patients were excluded because (i) there was no tissue available for confirmation of the diagnosis and further analysis (8), (ii) squamous cell histology (7), (iii) lack of clinical data (11), or (iv) the absence of radiologically or histologically confirmed BMets or LC (3) (Figure 1).

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.