Analysis of K-ras mutations and expression of cyclooxygenase-2 and gastrin protein in laterally spreading tumors.
OBJECTIVE
Recent advances in colonoscopic techniques have led to the increased detection of, and interest in, superficial type colorectal tumors, and a new category, the 'laterally spreading tumor (LST)', has been proposed. However, the characteristics of the genetic alterations in these LSTs have not yet been fully determined. We therefore classified LSTs as LST-granular (LST-G) or LST-non-granular (LST-NG), according to their macroscopic appearance, and examined the genetic alterations in these two tumor groups compared with those in protruded type tumors.


METHODS
We obtained a total of 62 colorectal tumors, including 26 protruded type, 17 LST-G and 19 LST-NG, from specimens resected surgically or endoscopically. We examined K-ras codon 12 mutations by using the polymerase chain reaction-restriction fragment length polymorphism method and by fluorescence direct sequencing. We also performed immunohistochemistry to analyze cyclooxygenase (COX)-2 and gastrin abnormalities.


RESULTS
The incidence of K-ras mutation was 50.0% in protruded type tumors, 76.5% in LST-G, and 26.3% in LST-NG. The frequencies of COX-2 overexpression were 73.1, 88.2, and 31.6%, respectively, and those of gastrin overexpression were 61.5, 82.4, and 26.3%, respectively. Therefore, LST-G is similar to protruded type tumors in that the incidence of K-ras mutation and the frequencies of COX-2 and gastrin overexpression are high. LST-NG differs from both of these tumor types in that the values of these three indicators are all low.


CONCLUSIONS
These results show that LST-G and LST-NG have different genetic alterations.
Mukawa
Kenichiroh
K
Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi, Japan.
Fujii
Shigehiko
S
Takeda
Jun
J
Kitajima
Kazuaki
K
Tominaga
Keiichi
K
Chibana
Yoko
Y
Fujita
Mikio
M
Ichikawa
Kazuhito
K
Tomita
Shigeki
S
Ono
Yuko
Y
Imura
Johji
J
Kawamata
Hitoshi
H
Chiba
Tsutomu
T
Hiraishi
Hideyuki
H
Terano
Akira
A
Fujimori
Takahiro
T
D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D005787:Gene Frequency; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013194:Staining and Labeling
D005755:Gastrins; D051546:Cyclooxygenase 2