Venous invasion and down-regulation of p21(WAF1/CIP1) are associated with metastasis in colorectal carcinomas.
OBJECTIVE
Liver and lymph node metastasis the major prognostic factor in patients with colorectal carcinoma. The aim of this work was to search for tumor parameters which can be employed to predict whether this has occurred.


METHODS
A total of 211 patients with a colorectal carcinoma (Dukes' B group, 83; Dukes' C, 94; Dukes' D, 34) were investigated for 10 clinicopathological variables, as well as apoptotic activity, expression of Ki-67, p21(WAF1/CIP1), p53, bcl-2 and DCC proteins, and the c-Ki-ras mutations. Data were analyzed by univariate and multivariate statistics.


RESULTS
Lymph node metastasis-predictive models were developed using the venous involvement index (the number of vascular involvements per elastica van Gieson-stained slide; Odds ratio [OR], 2.38; 95% confidence interval [CI], 1.52-3.71; p=0.0001), tumor size (OR, 0.82; 95% CI, 0.70-0.97; p=0.0179), and p21(WAF1/CIP1) immunolabeled index (the percentages of positive tumor cells; OR, 0.76; 95% CI, 0.64-0.90; p=0.0011). Liver metastasis-predictive models were developed using the venous involvement index (OR, 2.40; 95% CI, 1.71-3.37; p=0.0000) and tumor location (rectum vs. colon; OR, 9.31; 95% CI, 2.41-36.01; p=0.0012).


CONCLUSIONS
Down-regulation of p21(WAF1/CIP1) as well as marked venous involvement, small tumor size and colonic tumor are associated with lymph node and/or liver metastasis. Criteria for assessment of metastasis risk provide a basis for additional treatment guidelines.
Mitomi
Hiroyuki
H
Department of Clinical Research Laboratory, Pathology Division, National Hospital Organization Sagamihara Hospital, Kanagawa, Japan. h-mitomi@sagamihara-hosp.gr.jp
Mori
Akio
A
Kanazawa
Hideki
H
Nishiyama
Yasuhiko
Y
Ihara
Atsushi
A
Otani
Yoshimasa
Y
Sada
Miwa
M
Kobayashi
Kiyonori
K
Igarashi
Masahiro
M
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen