Comparative analysis of prognostic significance of molecular markers of apoptosis with clinical stage and tumor differentiation in patients with colorectal cancer: a single institute experience.
OBJECTIVE
The most important parameter determining the outcome of colorectal cancer (CRC) is the presence of metastases, which occur in 45-50% of all cases. The balance between proliferation and apoptosis is a key factor for tumor growth, and thus--for metastasis. Evaluation of markers for proliferation and apoptosis could therefore be helpful in predicting tumor behavior in early stage of carcinogenesis.


METHODS
Seventy-two biopsies from cases of colorectal cancer (CRC) were immunostained for the proliferation/apoptosis-related proteins Bcl-2, Bax and p53. The resected specimens were also subjected for routine pathologic assessment as part of Tumor, Node and Metastases (TNM) staging.


RESULTS
Comparing the marker protein expression with standard prognostic factors such as clinical stage and grade of differentiation revealed a lack of correlation between markers and standard prognostic factors in cases where clinical stage favors good prognosis (I and II stage). We found lack of correlation in 52% of diagnosed patients by tumor grade and 46% in patients by clinical stage.


CONCLUSIONS
Co-expression of Bax with p53 protein is associated with poor clinical outcome, especially in cases without concomitant expression of bcl-2. The blocked apoptosis and inability of the organism to "liquidate" the neoplastic transformation of the cell (loss/mutation of p53), which we establish in our study in the half the patients with high and moderately differentiated carcinoma and separately in 46% of the patients with favorable prognosis by clinical stage is a reason for fast progression, too. The presence of a low correlation between the staging and the results of the molecular profiling suggest that the staging system needs to improve to address more precisely the issues of therapeutic options and patient survival. Using a panel of markers rather than a single marker is a step in this direction.
Ivanov
K
K
Department of Colorectal Surgery, I-st Clinic of Surgery, University Hospital "St. Marina", Medical University, Varna, Bulgaria.
Kolev
N
N
Tonev
A
A
Nikolova
G
G
Krasnaliev
I
I
Softova
E
E
Tonchev
A
A
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein