P53 Overexpression In Patients Research Articles

Prognostic significance of p53 in gastric cancer: a meta- analysis.

Gastric cancer is one of the frequently seen cancers in the world and it is the second most common reason for death due to cancer. The prognostic role of expression of p53 detected by immunohistochemistry in gastric cancer remains controversial. This meta-analysis aimed to explore any association between overexpression and survival outcomes. We systematically searched for studies investigating the relationships between expression of p53 detected by immunohistochemistry and prognosis of gastric cancer patients. Study quality was assessed using the Newcastle-Ottawa Scale. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios for overall survival and disease-free survival. A total of 4.330 patients from 21 studies were included in the analysis. Our results showed tissue p53 overexpression in patients with gastric cancer to be associated with poor prognosis in terms of overall survival (HR, 1.610; 95% CI, 1.394 -5.235; p: <0.001). Pooled hazard ratio for disease free survival showed that p53 positivity or negativity were not statitistically significant (HR, 1.219; 95%CI, 0.782-1.899; p:0.382). The present meta-analysis indicated overexpression of p53 detected by immunohistochemistry to be associated with a poor prognosis in patients with gastric cancer.

Prognostic significance of breast cancer subtype and p53 overexpression in patients with locally advanced or high-risk breast cancer treated using upfront modified radical mastectomy with or without post-mastectomy radiation therapy

Although post-mastectomy radiation therapy (PMRT) has shown benefits, its effects in patient subpopulations remain uncertain. Therefore, we assessed whether breast cancer subtype and p53 overexpression were associated with outcome after modified radical mastectomy (MRM), with or without PMRT. We retrospectively analyzed the records of patients who underwent MRM, with or without PMRT, between January 1991 and December 2008. Patients were considered eligible if they had T3 or T4 stage disease; any T stage with N2 or N3 stage; any T or N stage with positive, close (<1 mm) resection margins; or skin, nipple, or pectoral muscle invasion. We used immunohistochemistry and/or fluorescent in situ hybridization to determine breast cancer subtypes and p53 overexpression status. We found that 104 patients were eligible, including 59 (56.7%) who underwent PMRT and 45 (43.3%) who did not. Median follow-up duration was 61.3 months (range 16.1-232.7). Overall survival (OS) was significantly longer in patients who underwent PMRT (P = 0.029). This trend was evident in the subgroup of luminal type A breast cancer (P = 0.017) and non-p53 overexpression (P = 0.026) patients. However, there was no significant survival benefit from PMRT in the subgroup of triple negative (TN) breast cancer (P = 0.528) and p53 overexpression (P = 0.189) patients. The benefit of PMRT differed among subgroups with different breast cancer subtype and p53 overexpression. More efficacious systemic treatment strategies are needed, especially in patients at high risk for distant metastasis, to obtain optimal therapeutic gain.

Prognostic Value of p53 Overexpression in Patients with Pathologic Stage I Non-small Cell Lung Cancer

연구배경: p53 유전자의 돌연변이가 모든 조직형의 폐암에서 가장 흔한 유전적 이상으로 알려져 있다. 이전의 연구에도 불구하고, 폐암 조직에서 p53 단백질의 과발현과 생존과의 관계에 대해서는 아직도 논란이 있다. 본 연구의 목적은 수술로 절제한 병리학적 병기 1기인 비소세포폐암 환자에서 p53 단백질 과발현과 관련된 임상적 특징을 평가하고, p53 단백질 과발현과 예후와의 관계를 평가하는 것이다. 방법: 본 연구는 삼성서울병원에서 2003년 1월부터 2004년 6월까지 폐암으로 치료 받은 환자 중 병리학적 병기 제 1기의 비소세포폐암 환자를 대상으로 한 후향적 연구이다. 폐암 환자의 종양 조직을 이용하여 p53 단백질에 대한 면역조직화학 염색이 시행되었다. 성별, 연령, 흡연력, 조직형 및 병기 등의 임상적 특징들에 따른 p53 과발현 여부를 단변량 및 다변량 분석으로 평가하였다. 한편, p53의 과발현 여부에 따른 DFS, DSS 및 OS은 Kaplan-Meier 방법으로 평가하였고, 군간 비교는 log-rank test를 이용하였다. 결과: 125명의 연구 대상 환자에서 p53 면역 염색양성 종양 세포 빈도의 중앙값은 10%였다. 편평세포암에서 p53 과발현(≥10%)의 빈도가 66%로 선암의 38%보다 통계적으로 유의하게 증가되어 있었다(p=0.002). 병리학적 병기가 IB인 경우 p53 과발현의 빈도가 59%로 IA의 38%보다 증가되어 있었다(p=0.024). 흡연의 기간은 p53이 과발현 된 경우(27년)에 그렇지 않은 경우(20년)보다 통계적으로 유의하게 길었다(p=0.032). 25갑년 이상의 흡연력도 p53이 과발현 된 경우(58%)에 그렇지 않은 경우(38%)보다 더 흔하게 관찰되었다(p=0.024). 다변량 분석에서 p53 과발현과 관련된 인자는 편평세포암의 조직형뿐인 것으로 평가 되었다(p=0.002). 한편, p53 과발현 여부에 따른 DFS, DSS 및 OS의 차이는 없었으며, 편평세포암과 선암의 세부 군 분석에서도 생존의 차이는 없었다. 결론: 수술로 절제한 제 1기 비소세포폐암 조직에서 면역조직화학 염색으로 평가한 p53 과발현은 조직형, 병기 및 흡연력과 관련이 있었고, 다변량 분석에서 조직형만이 p53 과발현과 관련된 독립적 인자였다. 하지만, p53 과발현과 환자의 생존과는 관련이 없었다.

Prognostic value of overexpression of p53 in human ovarian carcinoma patients receiving cisplatin

A major obstacle to the treatment of ovarian carcinoma is intrinsic/acquired resistance to cisplatin-based chemotherapy. The clinical significance of p53 overexpression in patients with ovarian carcinoma is still controversial. The aim of this study was to investigate the independent prognostic significance of p53 overexpression in patients with ovarian carcinoma who are treated with cisplatin. We retrospectively examined the overexpression of p53 in primary ovarian carcinoma, and its association with chemotherapeutic efficacy. One hundred and thirty four ovarian carcinomas were surgically removed from patients who received adjuvant cisplatin-based chemotherapy. Immunohistochemical analysis of p53 was performed using a DO7 antibody against the p53 protein in 134 ovarian carcinomas. The significance of p53 in the prognosis of patients with ovarian carcinomas was also examined by a survival analysis of mortality follow-up data covering the period from 1988 to 2001. Thirty-three tumors (25%) exhibited p53 overexpression. Overexpression of p53 in grade 2/grade 3 tumors was significantly higher than that seen in grade 1 tumors ( P=0.0088, 0.0229). Patients with tumors who also showed overexpression of p53 had a significantly inferior response to chemotherapy compared with the patients with p53-negative tumors ( P=0.04). Cox regression analysis revealed that p53 overexpression was prognostic for poor disease outcome after adjustment for FIGO stage, grade and residual tumor. These findings suggest that overexpression of p53 in ovarian carcinoma is associated with unfavorable clinical outcome in patients treated with cisplatin-based chemotherapy. Therefore, detection of p53 overexpression using the DO7 antibody may be considered as a predictive marker of chemoresistance for cisplatin in patients with ovarian carcinoma.

Immunohistochemical determination of p53 protein does not predict clinical response in advanced colorectal cancer with low thymidylate synthase expression receiving a bolus 5-fluorouracil—leucovorin combination

We assessed the hypothesis that a compromised p53 function could account for the non response of colon cancer patients with low thymidylate synthase (TS) expression receiving a bolus 5-fluorouracil (5-FU) leucovorin (LV) combination. The study population consisted of 41 patients with unresectable metastatic colon cancer, homogeneously, treated with bolus 5-FU and LV. Twenty-seven patients (66%) showed high levels of TS expression. The difference in the proportion of objective responses between patients with low (CR + PR: 7 of 14, 50%) and high (CR + PR: 0 of 27) TS levels was statistically significant (P = 0.0001, chi-square test). p53 nuclear over-expression was found in 27 of 41 patients (66%). No differences were observed in p53 overexpression in patients with high (66%) or low (66%) TS expression. p53 status was not found to be associated with response even in patients with low TS expression. p53 status measured by immunohistochemistry does not seem to be useful to identify unresponsive patients with low TS expression.

The prognostic value of p53 for long-term and recurrence-free survival following radical prostatectomy.

In the present study, 76 specimens (T1-T4) from 76 randomly selected patients undergoing radical prostatectomy at Hannover University as well as in the Josef Hospital Regensburg (13 patients) between 1980 and 1992 for whom tissue sections for immunohistochemical investigation were available, were investigated for different biological and clinical characteristics as predictors for long-term and recurrence-free survival: age, depth of tumour infiltration, histological grade, lymph node status, as well as overexpression of the p53 protein (monoclonal antibody DO-1). After a median follow-up of 50 months, 6 of 18 patients (33%) with more than 20% of tumour cells stained positively for p53 died from tumour progression compared with 9 of 58 patients (16%) with less than 20% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.011), histological grading (P = 0.009) and tumour stage (P = 0.024) were significant prognostic factors for survival, among which only p53 overexpression (P = 0.026) remained an independent significant predictor in multivariate analysis. Additionally, 18 of 66 patients (27%) with less than 40% positivity for p53 suffered tumour recurrence in contrast to 6 of 10 patients (60%) with more than 40% tumour cells exhibiting a positive staining reaction. In multivariate analysis, p53 overexpression was identified as the only prognostic parameter for recurrence-free survival (P = 0.005). Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with localised prostate cancer. The availability of more refined prognostic factors should assist decision making regarding the value of radical prostatectomy versus a surveillance strategy for prognostically defined subgroups of patients.

P53 overexpression is Not an independent prognostic factor for patients with primary ovarian epithelial cancer

BACKGROUND The clinical significance of p53 overexpression in patients with ovarian carcinoma is uncertain. Previous studies have yielded conflicting results and have been hampered by small patient populations, failure to account for other well-known prognostic variables in multivariate analysis, and failure to account for the grade of p53 overexpression. The aim of this study was to investigate the independent prognostic significance of p53 overexpression in patients with primary ovarian epithelial cancer (POEC). METHODS Tumors obtained from 221 patients with primary ovarian epithelial cancer (POEC) (Stages I-IV) were studied for p53 overexpression semiquantitatively by immunohistochemical techniques. The median duration of follow-up of surviving patients was 7 years. The presence or absence and degree of p53 overexpression were correlated with the clinicopathologic features of the study population and overall survival. Survival curves were constructed according to the Kaplan-Meier method, and differences in survival were assessed with the log rank test. The prognostic significance of p53 overexpression for survival was assessed in a multivariate analysis with the Cox proportional hazards model. RESULTS One hundred seven tumors (48.4%) exhibited p53 overexpression. The overexpression was graded as mild in 16.7% of cases, moderate in 5.9%, and strong in 25.8%. p53 overexpression was associated with advanced stage (P = 0.04), higher grade (P = 0.0003), serous histology (P = 0.0018), and patient age > 61 years (P = 0.013). In univariate analysis, p53 overexpression was a significant prognostic factor (P = 0.049 for any degree of overexpression, P = 0.03 for strong overexpression). However, in multivariate analysis, after adjustment for stage and size of residual tumor following cytoreductive surgery, p53 overexpression did not retain statistical significance. Survival curves for patients with different stages and grades of tumor differentiation did not demonstrate a difference in survival among patients with no p53 overexpression, compared with those who demonstrated any degree of p53 overexpression or compared with those who demonstrated strong p53 overexpression. CONCLUSIONS p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer. Cancer 1997; 80:892-8. © 1997 American Cancer Society.

P53 overexpression is Not an independent prognostic factor for patients with primary ovarian epithelial cancer

The clinical significance of p53 overexpression in patients with ovarian carcinoma is uncertain. Previous studies have yielded conflicting results and have been hampered by small patient populations, failure to account for other well-known prognostic variables in multivariate analysis, and failure to account for the grade of p53 overexpression. The aim of this study was to investigate the independent prognostic significance of p53 overexpression in patients with primary ovarian epithelial cancer (POEC). Tumors obtained from 221 patients with primary ovarian epithelial cancer (POEC) (Stages I-IV) were studied for p53 overexpression semiquantitatively by immunohistochemical techniques. The median duration of follow-up of surviving patients was 7 years. The presence or absence and degree of p53 overexpression were correlated with the clinicopathologic features of the study population and overall survival. Survival curves were constructed according to the Kaplan-Meier method, and differences in survival were assessed with the log rank test. The prognostic significance of p53 overexpression for survival was assessed in a multivariate analysis with the Cox proportional hazards model. One hundred seven tumors (48.4%) exhibited p53 overexpression. The overexpression was graded as mild in 16.7% of cases, moderate in 5.9%, and strong in 25.8%. p53 overexpression was associated with advanced stage (P = 0.04), higher grade (P = 0.0003), serous histology (P = 0.0018), and patient age > 61 years (P = 0.013). In univariate analysis, p53 overexpression was a significant prognostic factor (P = 0.049 for any degree of overexpression, P = 0.03 for strong overexpression). However, in multivariate analysis, after adjustment for stage and size of residual tumor following cytoreductive surgery, p53 overexpression did not retain statistical significance. Survival curves for patients with different stages and grades of tumor differentiation did not demonstrate a difference in survival among patients with no p53 overexpression, compared with those who demonstrated any degree of p53 overexpression or compared with those who demonstrated strong p53 overexpression. p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer.

P53 Expression in Hepatocellular Carcinoma in Greece: Correlation with Epidemiological and Histopathological Data

Localization of p53 oncoprotein was investigated in 60 hepatocellular carcinomas (HCCs) from patients resident in the Northwest and Central Greece. The streptavidin-biotin complex immunoperoxidase method was performed in archival formalin-fixed, paraffin-embedded material, using the monoclonal antibody DO-1. The aim of our study was to correlate p53 expression with histological and epidemiological data. p53 overexpression in patients with serological hepatitis B or C was greater (47%) as compared to that observed in patients without these markers (p < 0.01). Morphologically normal liver tissue (NLT) and liver cell dysplasia (LCD) was recognized adjacent to HCC developing on non-alcoholic cirrhotic livers in patients with "NonA, NonB hepatitis" from between 1975-1986. NLT and LCD and p53 oncoprotein was expressed in 10% of the cases. No relationship was observed between p53 expression and tumor histological grade, patients' age and sex. These results suggest that in Northwest and Central Greece, p53 oncosupressor gene may be involved in some HCCs; it may be associated with viral chronic infection disease (HBV or HCV), and as yet with uncharacterized viruses which remain to be determined.

P53 overexpression as a prognostic factor for advanced stage bladder cancer

Overexpression of the TP53 gene protein detected by immunohistochemistry appears to identify those patients with superficial bladder cancer at risk of the development of muscle invasive or metastatic disease. However, the role of p53 overexpression in patients with advanced or metastatic bladder cancer is not yet well established. In the present study, 44 specimens from 44 patients with advanced stage bladder tumours (T2-T4) undergoing radical cystectomy were investigated for different biological and clinical characteristics as possible prognostic factors: sex, age, depth of tumour infiltration, T-stage, histological grade, lymph node status, application of adjuvant systemic chemotherapy (MVAC), proliferative activity (staining for proliferating cell nuclear antigen (PCNA) by monoclonal antibody (PC10) as well as overexpression of the p53 oncoprotein (monoclonal antibody pAb 1801)). After a median follow-up of 22 months, 16 of the 23 patients (70%) with more than 40% of tumour cells stained positively for p53 (Group B) died from tumour progression compared with 7 of the 21 patients (33%) with less than 40% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.008), staining for PCNA (> or = 80% of cells positive) (P = 0.01) and tumour stage (P = 0.01) were significant prognostic factors for survival, among which p53 overexpression (P = 0.023) as well as T-stage (P = 0.012) remained independent significant predictors during multivariate analysis. Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with advanced bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for prognostically defined subgroups of patients.

P53 and lung cancer — More frequent p53 overexpression in patients with multiple primary tumours: Rott T, Poljak M, Stanisa O, Orel J, Debeljak A. Institute of Pathology, Faculty of Medicine, University Medical Centre. Korytkova 2, 61105 Ljubljana. Radiol Oncol 1994;28:271–275

p53 and lung cancer — More frequent p53 overexpression in patients with multiple primary tumours: Rott T, Poljak M, Stanisa O, Orel J, Debeljak A. Institute of Pathology, Faculty of Medicine, University Medical Centre. Korytkova 2, 61105 Ljubljana. Radiol Oncol 1994;28:271–275

Growth pattern and p53 overexpression in patients with early gastric cancer.

The growth pattern of early gastric carcinoma, based on a volumetric analysis, reflects well biologic characteristics of the tumor. The penetrating growth (Pen) type tumor has an unfavorable prognosis, compared with a superficially spreading (Super) type. Abnormality of the p53 suppressor gene plays an important role in alteration of cells leading to development of cancer. p53 point mutations are present even in an early stage of carcinoma. In 159 patients with early gastric carcinoma, overexpression of p53 was studied immunohistochemically, using a monoclonal antibody (PAb 1801), and the relationship between growth pattern and p53 overexpression was analyzed. Early gastric carcinoma was grouped into 43 of the Super type, 37 of the expansively penetrating growth (Pen-A) type, 16 of the infiltratively penetrating growth (Pen-B) type, and 63 of the Small mucosal type limited to the mucosal layer. The Pen-A type tumors were characterized by the highest incidence of p53 positive expression and poorest postoperative course. Between the Pen-A type and the Super type, there were significant differences in the incidence of the p53 positive expression (43% vs. 16%), the frequency of recurrence (16% vs. 7%), and disease free interval (574 days vs. 2926 days). The authors' observations show that the p53 gene plays an important role in expansion of gastric carcinoma, even in the early stages.