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Objective: To analyze the prognostic value of p53 protein as a marker of recurrence risk in each tumoral stage., Patients and Method: A prospective study of a cohort of 288 patients who underwent surgery for colorectal adenocarcinoma was performed. Stage 1 of the tumor-node-metastasis (TNM) classification was found in 42 patients (14.6%), stage II in 144 (50%) and stage III in 102 (35.4%). Histopathological variables were examined in tumor samples fixed in formol and embedded in paraffin and p53 (DO7 antibody) and proliferative cell nuclear antigen (PC-10 antibody) proteins were determined using immunohistochemistry. The results of p53 were analyzed in each of the categories of clinical and histopathological variables. Recurrence-free survival was calculated using the Kaplan-Meier method. The value of each variable as a predictive marker for tumoral recurrence was analyzed using Cox regression analysis. Hazard ratios and 95% confidence intervals were calculated as indicators of relative risk. The analysis was applied to the whole cohort and was subsequently repeated in each TNM tumoral stage separately., Results: Tumors with p53 protein overexpression more frequently recurred and showed lower recurrence-free survival at 5 years. However, the association between p53 expression and postoperative outcome was statistically significant in stage III tumors only. In this subgroup of patients, recurrence-free survival at 60 months was 60% in p53-negative tumors and was 26% in p53-positive tumors (p=0.010). In the multivariate analysis, p53 was an independent prognostic factor associated with a high risk of recurrence in stage III tumors (hazard ratio=2.76; 95% CI, 1.29-5.9; p=0.009). Overexpression of p53 showed prognostic value as a marker of high risk of recurrence in the form of metastases (hazard ratio=2.23; 95% CI, 1.04-4.75), but not as a prognostic marker of locoregional recurrence. No relationship was found between the state of p53 protein and the effect of postoperative adjuvant therapy., Conclusion: The p53 protein does not have the same prognostic value in all tumoral stages. This protein is only predictive of high recurrence risk in the subgroup of patients with stage III tumors.

Objectives: To investigate the relationship between the histopathologic effects of preoperative chemoradiotherapy in rectal cancer and the proteins, proliferating cell nuclear antigen (PCNA) and p53., Methods: Samples from 73 tumors were examined. The histopathologic effects observed in the resected specimens induced by preoperative chemoradiotherapy were correlated with the inmunohistochemical expression of PCNA and p53 in biopsies obtained by rectoscopy before chemoradiotherapy., Results: Thirty-five tumors showed a high PCNA index (48%). Nuclear accumulation of p53 protein was detected in 53 tumors (72%). Specimens were assigned one of four grades based on the amount of residual viable tumor. Three neoplasms (4%) showed complete regression; 8 other carcinomas (11%) showed only small numbers of tumor cells scattered within the field of stromal reaction. In these cases, it was considered that the tumor had responded significantly to radiotherapy. Tumors with a high PCNA index responded to chemoradiotherapy more frequently (8/35; 72%) than tumors with a low index (3/38; 43%) (p = 0.07). p53-negative tumors responded more frequently (4/20; 20%) than positive tumors (7/53; 13.2%) (p = 0.50). When pathologic and immunohistochemical characteristics of the tumors were included in a logistic regression model, only high PCNA index (odds ratio 5.35, 95% confidence interval 1.07-26.7) (p = 0.04) was significantly associated with the histologic response to preoperative chemoradiotherapy., Conclusion: High proliferative activity of rectal cancer, as determined by PCNA immunostaining, is predictive of the response to preoperative chemoradiotherapy., (Copyright 2003 S. Karger AG, Basel)

Background: The aim of the present study was to evaluate the influence of p53 protein on the survival of patients undergoing radical gastrectomy and postoperative adjuvant chemotherapy for gastric cancer., Patients and Methods: It was a retrospective study of 46 patients with gastric adenocarcinoma (Stage II and III of the Japanese staging system). Alypatients were treated by curative radical gastrectomy with regional lymphadenectomy plus adjuvant chemotherapy. This regime included Mitomycin (20 mg one hour before surgery, followed by 10 mg the day after) and Fluorinated Pyrimidine (UFT) (400 mg/m2/day orally) (started four weeks after operation, and continued for one year). Immunohistochemical expression of p53 protein was determined on tumor samples from the removed specimens. The influence of p53 on survival was assessed in a Cox's proportional hazard regression analysis., Results: Sixteen tumors (34.7%) manifested nuclear overexpression of p53 protein. Patients with p53-negative tumors showed higher cumulative survival at 4 years follow-up than patients with p53-positive tumors (82% versus 45%) (p < 0.01). Multivariate analysis identified p53 overexpression as a negative independent predictive factor (hazard ratio: 11.15) (95% CI: 1.93-64.42). Multivariate analysis performed on patients with Stage III tumors, separately, confirmed the predictive effect of p53 overexpression., Conclusion: The results suggest that postoperative adjuvant chemotherapy acted differently in p53-positive than in p53-negative gastric tumors. Absence of p53 overexpression is associated to longer survival when adjuvant therapy is administered.

Background: The prevalence of genetic alterations is different in primary carcinomas from the proximal colon when compared with carcinomas from the distal colorectum. The objective of this work was to explore the existence of possible differences in the informative weight of the risk of tumor recurrence provided by p53 immunostaining depending on the localization of the neoplasm., Patients and Methods: Nuclear immunohistochemical expression of p53 protein was determined in formalin-fixed paraffin-embedded archival tumor tissue samples from 190 primary colorectal adenocarcinomas. The relative prognostic importance on the risk of recurrence of each variable was assessed in a Cox's proportional hazard regression analysis. Multiplicative interaction terms between p53 and tumor site were included in the multivariate models in order to test their joint effect on survival., Results: One hundred and one patients (53.1%) manifested nuclear accumulation of the protein. P53 overexpression was more frequent in distal than in proximal tumors (58.5% ve s 41.7%) (p = 0.03). Disease-free survival was lower in p53-positive cases (75% versus 38%) (p = 0.006), but significance of the association varied according to the localization of the tumor (p = 0.004 in proximal carcinomas and p = 0.049 in distal carcinomas). Multivariate analysis identified p53 positivity and distal tumor localization as the factors significantly associated with a high risk of recurrence Interaction between p53 expression and localization was present. P53 exhibited different prognostic value in distal and proximal colon. While adjusted hazard ratio for positive p53 was 1.99 in distal cancers, it was 8.04 for proximal tumors., Conclusion: The prognostic with value of tumor recurrence associated overexpression of p53 protein is influenced by the location of the tumor. The negative predictive weight is significantly higher in proximal than in distal cancers.

Background: This study examined the prognostic information regarding the risk of postoperative tumor recurrence obtained by simultaneous determination of preoperative serum carcinoembryonic antigen (CEA) and immunohistochemical expression of p53 protein in tumor tissue from patients with colorectal carcinoma., Methods: A retrospective study of 174 patients (AJCC/UICC Stages I, II and III) was conducted. Serum CEA levels were determined by an enzyme-linked immunoadsorbent assay. Immunohistochemical expression of nuclear p53 protein was assessed in formalin fixed, paraffin embedded archival tumor tissue. The results of both factors were categorized by clinical and histopathologic variables. The relative prognostic significance of all factors with regard to disease free survival was assessed by Cox proportional hazards regression analysis. The stability of the predictive value of both markers was assessed: 1) by splitting the follow-up into three intervals and performing separate analyses for each period and 2) graphically by plotting the corresponding cumulative hazards ratio along the follow-up., Results: Eighty-two (47%) tumors manifested overexpression of p53 protein and 60 tumors (34.4%) exhibited elevated serum CEA levels (cutoff value of 5 ng/mL). p53 positive immunostaining and elevated CEA levels were associated with low cumulative disease free survival at 60 months' of follow-up, and proved to have independent prognostic significance. Analysis performed in different time periods of follow-up showed that the prognostic effect of both markers was not stable over time. The predictive significance of CEA and p53 changed along the study periods. An elevated preoperative CEA level was an indicator of a high risk of recurrence only during the first 2 years after surgery (hazards ratio, 3.26; 95% confidence interval 95% CI, 1.65-6.42). The presence of p53 immunoreactivity in the primary tumor was an indicator of a high risk of recurrence only after the first year of follow-up (hazards ratio, 4.02; 95% CI, 1.68-9.6)., Conclusions: The serum CEA level and expression of p53 protein provide complementary prognostic information. Time-dependency of the prognostic influence of both parameters should be taken into consideration when establishing postoperative predictive estimations., (Copyright 2000 American Cancer Society.)

Objective: To determine the predictive value of p53 nuclear overexpression in comparison with established prognostic pathological features in colorectal adenocarcinoma., Patients and Methods: 61 patients operated on for cure between January 1989 an December 1991 were included. Expression of p53 protein was examined by immunohistochemistry in paraffin-embedded sections. Tumor localization, depth of bowel wall involvement, lymph nodes metastasis, vascular invasion and PCNA Labelling index were studied in all patients., Results: Nuclear staining was detected in 27 (44.2%) cases. Positivity was more frequent in tumors with venous invasion and in rectal cancer. p53-positive tumours exhibited a higher likelihood of relapse and lower survival. After adjustment for the other covariates, p53 overexpression was the only factor showing independent prognostic significance on the risk of recurrence. None of the factors analysed evinced independent significant relationship with the risk of death., Conclusion: Nuclear p53 protein overexpression is closely related to the development of postoperative recurrences and has higher predictive value than standard pathological variables.