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Clinical Cancer Research Vol. 10, 3082-3090, May 1, 2004
© 2004 American Association for Cancer Research


Molecular Oncology, Markers, Clinical Correlates

Molecular Differences between Sporadic Serrated and Conventional Colorectal Adenomas

Kazuo Konishi1, Toshiko Yamochi2, Reiko Makino1,3, Kazuhiro Kaneko1, Taikan Yamamoto1, Hisako Nozawa1, Atsushi Katagiri1, Hiroaki Ito1, Kentarou Nakayama4, Hidekazu Ota2, Keiji Mitamura1 and Michio Imawari1

1 Second Department of Internal Medicine, 2 Second Department of Pathology, and 3 Clinical Laboratory, Showa University School of Medicine, Tokyo, and 4 Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, Japan

Purpose: The purpose is to compare the molecular characteristics of serrated adenomas (SAs) with those of conventional adenomas (CADs) and hyperplastic polyps (HPs).

Experimental Design: We evaluated the proliferative activity and molecular alterations in 47 SAs (25 pure-type and 22 mixed-type), 71 CADs, and 23 HPs.

Results: The proliferative activity of SAs, as evaluated by Ki-67 expression, was intermediate between CADs and HPs. There was no significant difference in the incidence of KRAS or p53 mutations between the three histological groups. In the microsatellite instability (MSI) analysis, 21% of SAs (9 of 43) showed MSI at two or more loci (MSI-H); corresponding values were 5% of CADs (3 of 64) and 8% of HPs (1 of 13; SAs versus CADs, P = 0.0125). MSI-H was more likely to be found in pure-type SAs (36%; 8 of 22) than in mixed-type SAs (5%; 1 of 21; P = 0.0212). Loss of hMLH-1 expression was found in 8 of 9 SAs with MSI-H. The incidence of BRAF or KRAS mutations was 36 and 15% of SAs, respectively; the combined incidence of BRAF and KRAS mutations occurred in 49% of SAs. However, there was no significant difference in the incidence of BRAF or KRAS mutations between SAs with and without MSI-H.

Conclusions: Genetic instability is more frequently implicated in the tumorigenesis of SAs, especially pure-type SAs, than in that of CADs. In contrast, activation of the Ras/Raf/MEK/MAP kinase cascade by BRAF or KRAS mutation, independently of the genetic instability, may be associated with the progression of about half of SAs.




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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2004 by the American Association for Cancer Research.