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. 2010 Oct;5(10):1551-8.
doi: 10.1097/JTO.0b013e3181e9da60.

Novel epidermal growth factor receptor mutation-specific antibodies for non-small cell lung cancer: immunohistochemistry as a possible screening method for epidermal growth factor receptor mutations

Yasufumi Kato  1 , Nir Peled, Murry W Wynes, Koichi Yoshida, Marta Pardo, Celine Mascaux, Tatsuo Ohira, Masahiro Tsuboi, Jun Matsubayashi, Toshitaka Nagao, Norihiko Ikeda, Fred R Hirsch
Affiliations

Novel epidermal growth factor receptor mutation-specific antibodies for non-small cell lung cancer: immunohistochemistry as a possible screening method for epidermal growth factor receptor mutations

Yasufumi Kato et al. J Thorac Oncol. 2010 Oct.

Abstract

Background: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) predict better outcome to EGFR tyrosine kinase inhibitors. The most common mutations are exon 19 deletions (most frequently E746-A750) and L858R point mutation in exon 21. Here, we evaluated the accuracy of novel EGFR mutation-specific antibodies in a Japanese cohort with NSCLC and compared with direct DNA sequencing and clinical outcome.

Materials and methods: Immunohistochemistry (IHC) using antibodies specific for the E746-A750 and L858R mutations in EGFR was performed on tissue microarrays of tumors from 70 gefitinib treated NSCLC patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21.

Results: DNA sequencing showed EGFR mutations in 41 patients (58.6%) and exon 19 deletions in 18 patients (25.7%), 11 of 18 (61%) had a deletion in the range of E746-A750 and 12 (17.1%) had exon 21 mutations (L858R). IHC showed, for the E746-A750 and L858R mutations, sensitivity (81.8 and 75%), specificity (100 and 96.6%), positive predictive value (100 and 81.8%), and negative predictive value (96.7 and 94.9%). Analysis for objective response rates and survival were not correlated to IHC staining, although the combined staining showed nonsignificant trends toward better overall survival for patients with EGFR mutations.

Conclusions: The mutation-specific IHC antibodies have high sensitivity and specificity for predefined EFGR mutations and may be suitable for screening for these predefined mutations. However, negative IHC results require further mutation analyses before excluding EGFR-targeted therapy.

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Figures

Figure 1
Figure 1
Representative pictures of EGFR expression by immunohistochemical staining (40× magnification). A. DNA sequence E746-A750 deletion specimen stained with the E746-A750 specific antibody. Immunoreactivity is positive in the tumor cells but absent in non-tumor cells. B. DNA sequence L858R point mutation case. The tumor cells show no immunoreactivity with the E746-A750 specific antibody. C. L858R point mutation tumor showing tumor cells positive for L858R specific antibody. D. E746-A750 mutation case displaying no immunoreactivity in the tumor or non-tumor cells with the L858R specific antibody.
Figure 2
Figure 2
Overall survival (A) and progression free survival (B) based on dual mutation specific IHC staining for E746-A750 and L858R.
See this image and copyright information in PMC

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