The significance of tumor markers for proliferation and apoptosis in predicting survival in colorectal cancer.
OBJECTIVE
Clinicopathologic staging is even today the best prognostic factor in both colon and rectal cancers. There is still considerable variation in survival within the stages. To find other prognostic indicators we investigated six biologic markers associated with apoptosis and cell proliferation.


METHODS
Formalin-fixed, paraffin-embedded tissue samples of 363 patients with primary colon or rectal cancer of Dukes Stages A to D were chosen for immunohistochemical staining of five tumor markers: bcl-2, p53, Ki-67, cyclin D1, and carcinoembryonic antigen. Also, the number of apoptotic cells was studied by the terminal deoxynucleotidyl transferase-mediated D: -UTP nick end labeling method in 347 cases. The study was done on specially prepared tissue arrays.


RESULTS
In rectal cancer, patients with a Ki-67 labeling index of 5 percent or higher had a better prognosis than those with a lower index. Also, positive cytoplasmic p53 expression predicted a favorable outcome in rectal cancer. In colon cancer, positive nuclear staining of cyclin D1 reflected better survival. Weak and moderate staining of carcinoembryonic antigen correlated with better prognosis than strong staining, but negative staining predicted poor outcome. High apoptotic index of 100 or higher correlated with poor prognosis in colon cancer. However, in rectal cancer, the trend was the opposite. Bcl-2 staining tended to be more intense in samples of patients living 5 years or longer compared with those with worse prognosis.


CONCLUSIONS
Colon cancer and rectal cancer seem to have different biologic behavior, at least with respect to apoptosis, cytoplasmic p53 expression, and perhaps Ki-67 and carcinoembryonic antigen. Further studies are needed to clarify the significance of these factors.
Hilska
Marja
M
Department of Surgery, Turku University Central Hospital, Turku, Finland. marja.hilska@tyks.fi
Collan
Yrjö U
YU
O Laine
V Jukka
VJ
Kössi
Jyrki
J
Hirsimäki
Pirkko
P
Laato
Matti
M
Roberts
Peter J
PJ
D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000032:analysis / Q000096:biosynthesis; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012004:Rectal Neoplasms / Q000235:genetics / Q000473:pathology*; D013534:Survival; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53