Activating mutations of EGFR and the EML4-ALK translocation predict sensitivity to specific targeted therapies for lung cancer. Currently testing is generally performed by direct sequencing and ...fluorescence in situ hybridisation (FISH) respectively.
We trialled immunohistochemistry with mutation-specific antibodies for EGFR exon 19 (Cell Signalling catalogue 2085S) and EGFR EXON 21 (Cell Signalling catalogue 3197S) and ALK (Novacastra, clone 5A4) as screening tests for these targets.
Staining was performed on a TMA containing 231 resected non-small cell carcinomas including 151 adenocarcinomas. Six showed positive staining for EGFR exon 19 mutation, six for EGFR exon 21 and four for ALK. All 16 demonstrated adenocarcinoma histology and were subsequently shown to harbour the predicted activating mutation or translocation by sequencing and FISH.
Although our study was not intended or designed to assess the sensitivity of immunohistochemistry, we conclude that immuno-histochemistry is highly specific for these targets. We propose that immunohistochemistry may be used to triage all patients (including low risk patients) for formal sequencing or FISH analysis. If our results are confirmed by others, it may be appropriate to offer targeted therapies to those with positive immunohistochemistry and reserve sequencing/FISH for those cases negative by immu-nohistochemistry but considered to have a high clinical probability of these abnormalities.
Mutation specific immunohistochemistry (IHC) is a promising new technique to detect the presence of the BRAFV600E mutation in colorectal carcinoma (CRC). When performed in conjunction with mismatch ...repair (MMR) IHC, BRAFV600E IHC can help to further triage genetic testing for Lynch Syndrome. In a cohort of 1426 patients undergoing surgery from 2004 to 2009 we recently demonstrated that the combination of MMR and BRAFV600E IHC holds promise as a prognostic marker in CRC, particularly because of its ability to identify the poor prognosis MMR proficient (MMRp) BRAFV600E mutant subgroup. We attempted to validate combined MMR and BRAFV600E IHC as a prognostic indicator in a separate cohort comprising consecutive CRC patients undergoing surgery from 1998 to 2003. IHC was performed on a tissue microarray containing tissue from 1109 patients with CRC. The 5 year survivals stratified by staining patterns were: MMRd/BRAFwt 64%, MMRd/BRAFV600E 64%, MMRp/BRAFwt 60% and MMRp/BRAFV600E 53%. Using the poor prognosis MMRp/BRAFV600E phenotype as baseline, univariate Cox regression modelling demonstrated the following hazard ratios for death: MMRd/BRAFwt HR = 0.71 (95%CI = 0.40-1.27), p = 0.31; MMRd/BRAFV600E HR = 0.74 (95%CI = 0.51-1.07), p = 0.11 and MMRp/BRAFwt HR = 0.79 (95%CI = 0.60-1.04), p = 0.09. Although the findings did not reach statistical significance, this study supports the potential role of combined MMR and BRAF IHC as prognostic markers in CRC.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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