Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2.
About 40% of patients with colorectal carcinoma will develop local or distant tumour recurrences. Integrated analyses of bio-pathological markers, predictive of tumour aggressiveness, may offer a more rational approach to planning adjuvant therapy. To this end, we analysed the correlation between p53 accumulation, Bcl-2 expression, DNA ploidy, cell proliferation and conventional clinico-pathological parameters by testing the prognostic significance of these variables in a series of 171 colorectal carcinoma patients with long-term follow-up. The relationships among the various bio-pathological parameters, analysed by multiple correspondence analysis, showed 2 different clinico-biological profiles. The first, characterised by p53 negativity, Bcl-2 positivity, diploidy, low percentage of cells in S-phase (%S-phase), a low Ki-67 score, is associated with Dukes' A-B stage, well differentiated tumours and lack of relapse. The second, defined by p53 positivity, Bcl-2 negativity, aneuploidy, high %S-phase and elevated Ki-67 score, correlates with Dukes' C-D stage, poorly differentiated tumours and presence of relapse. When these parameters were examined according to Kaplan-Meier's method, significantly shorter disease-free (DFS) and overall survival (OS) were also observed in patients bearing p53 positive and Bcl-2 negative tumours, in Dukes' B stage. In multivariate analysis, p53 accumulation and Bcl-2 expression emerged as independent predictors of a worse and better clinical outcome, respectively. Our results indicate that, in colorectal adenocarcinomas, a biological profile, based on the combined evaluation of p53 and Bcl-2, may be useful for identifying high risk patients to be enrolled in an adjuvant setting, mainly in an early stage of the disease. Int. J. Cancer (Pred. Oncol.) 84:545-552, 1999.
Buglioni
S
S
Pathology Department, Regina Elena Cancer Institute, Rome, Italy.
D'Agnano
I
I
Cosimelli
M
M
Vasselli
S
S
D'Angelo
C
C
Tedesco
M
M
Zupi
G
G
Mottolese
M
M
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D000368:Aged; D002455:Cell Division; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011003:Ploidies; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012004:Rectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D012306:Risk; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53