title: Elevated microsatellite alterations at selected tetra-nucleotide (EMAST) in non-small cell lung cancers--a potential determinant of susceptibility to multiple malignancies.
abstract: The present study evaluated the potential clinicopathologic significance of elevated microsatellite alteration at selected tetra-nucleotide (EMAST) in non-small cell lung cancer (NSCLC). Sixty-five NSCLCs (19 squamous cell carcinomas, 39 adenocarcinomas, one adenosquamous cell carcinoma, and 6 large cell carcinomas) were examined for EMAST in the ten selected tetra-nucleotide markers. Traditional microsatellite instability (MSI) in the five mono- or di-nucleotide markers of the Bethesda panel was also examined, and compared with EMAST. The incidence of EMAST was higher than that of traditional MSI, as 64.6% (42/65) and 12.3% (8/65) tumors respectively exhibited EMAST and traditional MSI in at least one marker. EMAST and traditional MSI appear to occur independently, as no significant association in their incidence was found (Fisher's exact test, P = 0.146). Subjects who exhibited EMAST in two or more markers had a significantly higher incidence of history of other malignant neoplasms (42.9% [9/21]), compared to those with less than two markers (16.3% [7/43] (Chi-square test, P = 0.021)). Taken together, impairment of molecular machinery for maintaining stable replication of the tetra-nucleotide-repeating regions, which would differ from machinery for mono- or di-nucleotide-repeating regions, may elevate susceptibility to NSCLCs and certain neoplastic diseases. Elucidation of the potential molecular mechanism of EMAST is expected to lead to a discovery of a novel genetic background determining susceptibility to NSCLC and other multiple neoplasms. This is the first report describing a clinicopathologic significance of EMAST in NSCLC.
authors: Yokohama City University Medical Center, Yokohama, Japan. hiromasa@jg7.so-net.ne.jp
authors: Hiromasa
authors: H
authors: Arai
authors: Koji
authors: K
authors: Okudela
authors: Hisashi
authors: H
authors: Oshiro
authors: Noriko
authors: N
authors: Komitsu
authors: Hideaki
authors: H
authors: Mitsui
authors: Teppei
authors: T
authors: Nishii
authors: Masahiro
authors: M
authors: Tsuboi
authors: Akinori
authors: A
authors: Nozawa
authors: Yasuharu
authors: Y
authors: Noishiki
authors: Kenichi
authors: K
authors: Ohashi
authors: Kenji
authors: K
authors: Inui
authors: Munetaka
authors: M
authors: Masuda
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018196:Carcinoma, Adenosquamous / Q000235:genetics* / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000235:genetics* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000473:pathology
keywords: Non-small cell lung cancer; chromosomal instability; elevated microsatellite alteration at selected tetra-nucleotide; loss of heterozygosity; microsatellite instability; multiple malignant neoplasms