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Int J Clin Exp Pathol 2013;6(3):395-410

Original Article
Elevated microsatellite alterations at selected tetra-nucleotide (EMAST) in non-small cell
lung cancers—a potential determinant of susceptibility to multiple malignancies

Hiromasa Arai, Koji Okudela, Hisashi Oshiro, Noriko Komitsu, Hideaki Mitsui, Teppei Nishii, Masahiro Tsuboi, Akinori Nozawa, Yasuharu
Noishiki, Kenichi Ohashi, Kenji Inui, Munetaka Masuda

Respiratory Disease Center (Surgery) and Division of Pathology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku,
Yokohama, 232-0024, Japan; Department of Pathology, Artificial Organ Science and Surgery, Yokohama City University Graduate School of
Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan

Received November 12, 2012; Accepted December 23, 2012; Epub February 15, 2013; Published March 1, 2013

Abstract: The present study evaluated the potential clinicopathologic significance of elevated microsatellite alteration at selected tet-ra-
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. Tradi-
tional 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. (IJCEP1211012).

Keywords: Non-small cell lung cancer, elevated microsatellite alteration at selected tetra-nucleotide, microsatellite instability, chromosomal
instability, loss of heterozygosity, multiple malignant neoplasms

Address correspondence to: Hiromasa Arai, Respiratory Disease Center (Surgery), Yokohama City University Medical Center, 4-57 Urafune-
cho, Minami-ku, Yokohama, 232-0024, Japan. Tel: +81 45 2615656; Fax: +81 45 2539955; E-mail: hiromasa@jg7.so-net.ne.jp