Cdc2 as prognostic marker in stage UICC II colon carcinomas.
OBJECTIVE
Cyclin-dependent kinase 2 (cdc2) controls the G2-M checkpoint and, therefore, the entrance of cells into mitosis. It might play a crucial role during tumour progression in colon carcinomas (CCA). Thus, the prognostic value of cdc2 expression and connected markers relevant for proliferation and apoptosis has to be evaluated.


METHODS
Punch biopsies from the tumour centre and the invasion front of 0.6mm diameter from 392 CCA stage UICC II-IV were integrated in 14 recipient paraffin blocks. After immunohistochemical staining for cdc2, p53, caspase 3 and ki-67, a present (+) and absent (-) scoring was performed in the tissue arrays. The logrank test was used to compare distant metastasis and cancer-related survival. Multivariate Cox regression analysis was done to identify independent prognostic factors for parameters with significant influence on cancer-related survival (CRS) and distant metastasis (DM).


RESULTS
The pT-category (p=0.007), nodal status (p<0.001), extramural venous infiltration (p<0.001) and lymphatic vessel invasion (p=0.003) were identified as independent histological parameters for CRS. Univariate analysis relating to stage UICC II-IV CCA showed caspase 3 in the tumour centre (p=0.047) to be a prognostic marker for CRS. In stage UICC II cdc2 (p=0.041) and caspase 3 in the invasion front (p=0.026) could be identified as independent prognostic factors for CRS and DM by multivariate analysis.


CONCLUSIONS
Cdc2 and caspase 3 could be identified as independent prognostic markers in stage UICC II CCA. They might be of value to select patients who should receive adjuvant treatment.
Meyer
Alexander
A
Department of Surgery, Friedrich-Alexander University, Erlangen-Nuremberg, Germany.
Merkel
Susanne
S
Brückl
Wolfgang
W
Schellerer
Vera
V
Schildberg
Claus
C
Campean
Valentina
V
Hohenberger
Werner
W
Croner
Roland S
RS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016203:CDC2 Protein Kinase / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D053148:Caspase 3 / Q000032:analysis / Q000235:genetics*; D003110:Colonic Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate
D009363:Neoplasm Proteins; D016203:CDC2 Protein Kinase; D053148:Caspase 3