title: Significance of epidermal growth factor receptor gene mutations in squamous cell lung carcinoma.
abstract: Epidermal growth factor receptor (EGFR) gene mutations have been reported to be clinically significant in non-small cell lung cancer (NSCLC). However, because most previous studies focused only on adenocarcinomas, EGFR mutations in other histotypes are poorly investigated. We evaluated the frequency of EGFR gene mutations in squamous cell carcinoma (SCC) and its clinicopathological features. In total, 89 frozen tumor specimens that had been first diagnosed as SCCs, were examined for EGFR mutations in exons 19 and 21 using direct sequencing, PNA-enriched sequencing and SmartAmp2. Additionally, pathological investigation, including immunostaining for p63 and TTF-1, alcian blue staining and EGFR mutation-specific immunohistochemistry in mutation-positive samples was also performed. The frequency of EGFR mutations was 5.6% (5/89); all mutations were deletions in EGFR exon 19. Immunohistological investigation of these samples revealed that two of five were positive for p63 and TTF-1 staining, and showed production of mucin, as evidenced by alcian blue staining. Consequently, three of the samples were considered to be true SCC at final pathological diagnosis, while the remaining two samples were revised to adenosquamous carcinoma and adenocarcinoma. The final frequency of the EGFR mutations in true SCC was 3.4% (3/87). In conclusion, EGFR mutations were found in a small, but significant, number of SCC tumor samples and thus EGFR mutational analysis was useful in the accurate diagnosis of SCC. Our data demonstrate that EGFR mutational analysis should be performed not only in adenocarcinoma, but also in SCC to allow accurate diagnosis and treatment.
authors.affiliation: Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi 371-8511, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyamae
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Shimizu
authors.forename: Junko
authors.initials: J
authors.lastname: Hirato
authors.forename: Takuya
authors.initials: T
authors.lastname: Araki
authors.forename: Kazumi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Ogawa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kakegawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sugano
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Nakano
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Mitani
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Kaira
authors.forename: Izumi
authors.initials: I
authors.lastname: Takeyoshi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors