Immunohistochemical staining with EGFR mutation-specific antibodies: High specificity as a diagnostic marker for lung adenocarcinoma Journal Article


Authors: Wen, Y. H.; Brogi, E.; Hasanovic, A.; Ladanyi, M.; Soslow, R. A.; Chitale, D.; Shia, J.; Moreira, A. L.
Article Title: Immunohistochemical staining with EGFR mutation-specific antibodies: High specificity as a diagnostic marker for lung adenocarcinoma
Abstract: We previously demonstrated a high specificity of immunohistochemistry using epidermal growth factor receptor (EGFR) mutation-specific antibodies in lung adenocarcinoma and correlation with EGFR mutation analysis. In this study, we assessed EGFR mutation status by immunohistochemistry in a variety of extrapulmonary malignancies, especially those that frequently show EGFR overexpression. Tissue microarrays containing triplicate cores of breast carcinomas (n=300), colorectal carcinomas (n=65), pancreatic adenocarcinoma (n=145), and uterine carcinosarcoma or malignant mixed müllerian tumors (n=25) were included in the study. Tissue microarray of lung adenocarcinoma with known EGFR mutation status was used as reference. Immunohistochemistry was performed using antibodies specific for the E746-A750del and L858R mutations. In pulmonary adenocarcinoma, a staining intensity of 2+ or 3+ correlates with mutation status and is therefore considered as positive. Out of 300 breast carcinomas, 293 (98%) scored 0, 5 (2%) had 1+ staining, 2 (1%) were 2+ for the L858R antibody. All breast carcinomas scored 0 with the E746-A750 antibody. All the colorectal, pancreatic carcinomas and malignant mixed müllerian tumors were negative (0) for both antibodies. Molecular analysis of the breast carcinomas that scored 2+ for L858R showed no mutation. Our results show that EGFR mutation-specific antibodies could be an additional tool distinguishing primary versus metastatic carcinomas in the lung. False-positivity can be seen in breast carcinoma but is extremely rare (1%). © 2013 USCAP, Inc All rights reserved.
Keywords: immunohistochemistry; adult; human tissue; aged; primary tumor; gene mutation; major clinical study; cancer staging; gene overexpression; epidermal growth factor receptor; mutational analysis; tumor marker; colorectal carcinoma; liver metastasis; lung metastasis; lung adenocarcinoma; breast carcinoma; cancer size; pancreas adenocarcinoma; tissue microarray; epidermal growth factor receptor antibody; uterus carcinoma; mixed mullerian tumor; molecular diagnosis; triple-negative breast cancer; mutation-specific antibody
Journal Title: Modern Pathology
Volume: 26
Issue: 9
ISSN: 0893-3952
Publisher: Nature Research  
Date Published: 2013-09-01
Start Page: 1197
End Page: 1203
Language: English
DOI: 10.1038/modpathol.2013.53
PROVIDER: scopus
PUBMED: 23599147
PMCID: PMC4159955
DOI/URL:
Notes: --- - "Export Date: 1 October 2013" - "CODEN: MODPE" - "Source: Scopus"
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MSK Authors
  1. Andre L Moreira
    176 Moreira
  2. Dhananjay Arun Chitale
    33 Chitale
  3. Marc Ladanyi
    1326 Ladanyi
  4. Jinru Shia
    714 Shia
  5. Hannah Yong Wen
    301 Wen
  6. Robert Soslow
    793 Soslow
  7. Edi Brogi
    515 Brogi