Die Entwicklung eines prädiktiven Biomarker-Score für MET im Magenkarzinom

Aims: We aimed to develop a putative predictive biomarker score for future hepatocyte growth factor receptor (MET)-targeted therapy of gastric cancer (GC). Methods and results: MET expression and MET ampli- fication were analysed by immunohistochemistry (IHC) and chromogenic in-situ hybridization (CISH) in 470 GC patients. Immunostaining was documented with the HistoScore. The percentage area of MET- amplified tumour cell clones was assessed by virtual microscopy. The expression of MET was heterogeneous in primary and metastatic GC. Immunostaining inten- sity (MET-IHC 2+/3+) correlated with MET amplifica- tion and a positive MET status was defined by a combination of MET-IHC 2+ or 3+ with MET amplifica- tion, or MET-IHC 3+ without MET amplification. The prognostic significance of the MET status was indepen- dent from the percentage area of positive tumour cells (e.g. <10 versus ≥10%). MET-positive GCs were micro- satellite stable and of KRAS/PIK3CA wild-type. MET- positive GCs had a very poor prognosis, with a median survival of 5.4 months and a hazard ratio of 2.126. Conclusions: A combination of immunohistochemis- try and CISH is suitable to assess MET status. If MET status is used as a predictive biomarker, prospective studies should pay specific attention to adequate tis- sue sampling, should ignore cutoff values for tumour areas, may consider the KRAS and PIK3CA genotype as negative predictive markers and should carry out the analysis expeditiously.


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