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10.1245/s10434-008-9986-y
Annals of Surgical Oncology 15:2965-2975 (2008)
© 2008 Society of Surgical Oncology
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Original Article

SnoN Overexpression is Predictive of Poor Survival in Patients with Esophageal Squamous Cell Carcinoma

Ichiro Akagi, MD1, Masao Miyashita, MD, PhD1, Hiroshi Makino, MD, PhD1, Tsutomu Nomura, MD, PhD1, Nobutoshi Hagiwara, MD, PhD1, Ken Takahashi, MD, PhD1, Kazumitsu Cho, MD, PhD1, Takuya Mishima, MD, PhD2, Toshihiro Takizawa, MD, PhD2 and Takashi Tajiri, MD, PhD1

1 Departments of Surgery for Organ Function and Biological Regulation, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
2 Molecular Anatomy and Medicine, Nippon Medical School, Tokyo, Japan

Correspondence: Address correspondence and reprint requests to: Ichiro Akagi, MD; E-mail: ichiro{at}nms.ac.jp

Background: Earlier studies have identified the minimal overlapping region of amplification at 3q26 in esophageal squamous cell carcinoma (ESCC) by comparative genomic hybridization (CGH) analysis. These include PIK3CA which encodes the p110{alpha} catalytic subunit of phosphatidylinositol (PI) 3-kinase, a telomerase RNA component (TERC), a squamous cell carcinoma-related oncogene (SCCRO), ecotropic viral integration site-1 (EVI-1), and a Ski-related novel oncogene (SnoN). In the present study, we investigated the mRNA levels of four candidate genes (TERC, SCCRO, EVI-1, and SnoN) to determine whether genes other than PIK3CA are targets for amplification at 3q26 in ESCC. And also, we examined SnoN expression in ESCC samples.

Methods: Fifty-nine representative cases with ESCC were selected from our archives. We performed quantitative RT-PCR of four candidate genes (TERC, SCCRO, EVI-1, and SnoN) and immunohistochemistry for SnoN. Finally, we correlated these findings with the clinicopathological characteristics to determine their interrelationship.

Results: Among the four genes we tested, only SnoN mRNA was consistently overexpressed in primary ESCC, compared with those in corresponding nontumorous esophageal epithelia (P < 0.001). Immunoreactive SnoN was detectable in 31 of 59 (52.5%) esophageal squamous cell carcinoma specimens. The levels of SnoN expression were found to correlate with the depth of invasion and recurrence (P < 0.05). Furthermore, patients with positive staining for SnoN displayed more unfavorable outcomes than patients with negative staining (P < 0.05).

Conclusion: SnoN is likely to be the target of the amplification at 3q26 in ESCC and plays an important role in the development of ESCC, influencing disease-specific survival.

Key Words: Esophageal squamous cell carcinoma • Ski-related novel oncogene • SnoN • TERC • EVI-1 • SCCRO • TGF-β






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