Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis.
BACKGROUND
To identify the role of survivin, a novel inhibitor of apoptosis (IAP) in colorectal tumorigenesis, the authors investigated tissue expression of survivin in human colorectal tumors including 43 hyperplastic polyps, 171 adenomas with low dysplasia, 42 adenomas with high dysplasia, and 60 carcinomas in adenoma, and examined whether the expression of survivin correlated with tumor cell apoptosis, proliferation, and angiogenesis, which is known to initiate the imbalance between cell proliferation and apoptosis.


METHODS
Immunohistochemical staining for the paraffin sections by using the monoclonal antibodies, survivin, p53, bcl-2, Ki-67, and CD34, was performed by the standard avidin-biotin-peroxidase technique. The apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method, using an Apop Tag in situ detection kit.


RESULTS
The immunoreactivity of survivin significantly increased in the transition from adenoma with low dysplasia to high dysplasia/carcinoma (P < 0.001). Similar changes in protein expression were observed for p53 but not for bcl-2, which was expressed throughout the colorectal tumorigenesis. This transition was associated with a significant decrease in the apoptotic index (AI) and significant increases in the Ki-67 labeling index (LI) and microvessel density (MVD; P < 0.001 for both). The expression of survivin inversely correlated with AI and was positively correlated with Ki-67 LI and MVD (P < 0.001 for both).


CONCLUSIONS
These results suggest that, like p53, survivin plays an important role in transition from adenoma with low dysplasia to high dysplasia during human colorectal tumorigenesis.
Kawasaki
H
H
Department of General and Gastroenterological Surgery, Osaka Medical College, Takatsuki City, Osaka, Japan.
Toyoda
M
M
Shinohara
H
H
Okuda
J
J
Watanabe
I
I
Yamamoto
T
T
Tanaka
K
K
Tenjo
T
T
Tanigawa
N
N
D000236:Adenoma / Q000503:physiopathology*; D017209:Apoptosis; D002277:Carcinoma / Q000503:physiopathology*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D003111:Colonic Polyps / Q000503:physiopathology*; D015179:Colorectal Neoplasms / Q000503:physiopathology*; D015853:Cysteine Proteinase Inhibitors / Q000032:analysis / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009389:Neovascularization, Pathologic; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis; D000077022:Survivin
C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D000077022:Survivin