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%).
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Yong Hannah
authors.initials: YH
authors.lastname: Wen
authors.forename: Edi
authors.initials: E
authors.lastname: Brogi
authors.forename: Adnan
authors.initials: A
authors.lastname: Hasanovic
authors.forename: Marc
authors.initials: M
authors.lastname: Ladanyi
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Chitale
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.forename: Andre L
authors.initials: AL
authors.lastname: Moreira
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000556:secondary; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D014594:Uterine Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors