Protein markers in colorectal cancer: predictors of liver metastasis.
OBJECTIVE
To assess the significance of the expression of five protein markers (nm23, p53, c-erbB-2, u-PA, and VEGF) to the development of metastasis in colorectal cancer.


BACKGROUND
The metastatic cascade is a complex multistep process involving several genetic alterations, angiogenesis activation, and tissue proteolysis. Although the prognosis of colorectal cancer depends on the stage of the tumor, the development of metastasis is difficult to predict.


METHODS
Paraffin-embedded specimens of 58 patients who underwent surgery for colorectal cancer were retrospectively analyzed by immunohistochemistry, and the coexpression of these protein markers was related to patient outcome.


RESULTS
The risk of developing liver secondaries was correlated with the expression of nm23 protein (p < 0.0001); this was also the case in those patients with Dukes' stage B showing positive nm23 immunostaining (p = 0.006). The determination of the number of positive markers or the cumulative intensity score did not improve the predictive value over and above that of nm23 protein alone.


CONCLUSIONS
Expression of nm23 protein is correlated with the risk of developing liver metastasis. Its evaluation alone may help to determine which patients who have undergone apparently curative resection of a colorectal cancer have an increased risk of liver recurrence, especially those with Dukes' stage B tumors who might be considered for adjuvant chemotherapy.
Berney
C R
CR
Department of Surgery, Prince of Wales Hospital, University of New South Wales, Randwick, Australia.
Fisher
R J
RJ
Yang
J
J
Russell
P J
PJ
Crowe
P J
PJ
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000556:secondary*; D008222:Lymphokines / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D012189:Retrospective Studies; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000096:biosynthesis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D016228:Endothelial Growth Factors; D008222:Lymphokines; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D014568:Urokinase-Type Plasminogen Activator; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C517938:NME1 protein, human