Immunohistochemical and mutational analyses of beta-catenin, Ki-ras, and p53 in two subtypes of colorectal mucinous carcinoma.
OBJECTIVE
The adenoma-carcinoma sequence theory is accepted in carcinogenesis of colorectal carcinoma. To elucidate the nature and genetic alterations in colorectal mucinous carcinoma (MC), we analyzed clinical and pathological characteristics of colorectal MC and nonmucinous carcinoma (NMC), and, furthermore, we compared the prognoses and the statuses of the Wnt signaling pathway, Ki-ras, and p53 in these two subtypes.


METHODS
Samples of colorectal MC obtained by surgical resections from 41 patients during the period from 1980 to 1999 were classified into fixed (FIX) type and floating (FLO) type (22 and 19 cases, respectively). The statuses of the Wnt signaling pathway and p53 protein were estimated by immunohistochemistry of beta-catenin and p53 proteins, respectively. The mutations in the Ki-ras gene were examined by direct sequencing.


RESULTS
The prognosis of colorectal MC was poorer than that of NMC at both stage II and stage III (P = 0.0037 and <0.0001, respectively). The survival rate of patients with the FLO type of MC was lower than that of patients with the FIX type (P = 0.021). Although the results of immunohistochemistry of beta-catenin and mutational analysis of the Ki-ras gene in the two subtypes were not significantly different; the rate of positive nuclear staining of p53 was lower in the FLO type than in the FIX type (P = 0.04).


CONCLUSIONS
Colorectal MC, particularly the FLO type, has a more aggressive nature than does colorectal NMC. The FLO type of colorectal MC may develop through different mechanisms from those through which NMC and the FIX type develop.
Ikeda
Satoshi
S
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. sikeda@hiroshima-u.ac.jp
Shimizu
Yosuke
Y
Fujimori
Masahiko
M
Ishizaki
Yasuyo
Y
Kurihara
Takeshi
T
Ojima
Yasutomo
Y
Okajima
Masazumi
M
Asahara
Toshimasa
T
D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000368:Aged; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D015689:Oncogene Protein p21(ras) / Q000032:analysis / Q000235:genetics*; D016019:Survival Analysis; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003062:Codon; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D015689:Oncogene Protein p21(ras)