p53, bcl-2, and Bax Expression in Renal Cell Carcinoma

Objectives. Renal cell carcinomas often show a high degree of resistance to chemotherapy and radiation despite expressing normal function of the protein p53. The loss of control of apoptosis may also contribute to progression and resistance to treatment modalities and can be attributed to an interaction between p53 and the apoptotic regulators bcl-2 and Bax. To determine whether the expression of p53, bcl-2, or Bax could be correlated with outcome, we analyzed the expression pattern of these proteins in renal cell tumor samples.Methods. We examined 28 patients with clear cell renal cell carcinomas along with 7 patients with papillary renal cell carcinomas and 4 with renal oncocytomas. All renal cell carcinomas were clinically localized Stage pT2 with tumor size ranging from 4.0 to 10.3 cm (mean 6.23). Immunohistochemistry was performed on all samples and correlated with markers of outcome, including tumor grade, metastasis, recurrence, and overall survival rate.Results. In all clear cell tumors, the detection level of p53 expression was below the sensitivity of the assay, consistent with the reported infrequent incidence of p53 mutations in renal cell cancers. bcl-2 expression showed a significant correlation (P = 0.018) with higher tumor grade but could not be significantly correlated with other parameters examined including tumor recurrence, metastasis, or survival rate. The expression of Bax could similarly be correlated with higher tumor grade but with none of the other parameters.Conclusions. At the present time, the combination of both tumor grade and stage represents the best prognostic markers available. Adjunctive use of bcl-2 and Bax staining currently plays a minimal role in helping to further stratify patients at high risk for disease progression or recurrence.     

Prognostic significance of p53, bcl-2, and Bax expression in early breast cancer

BACKGROUND: The use of adjuvant chemotherapy in early breast carcinoma is controversial, with most advocating its use in high-risk patients as defined by specific clinicopathologic parameters. Both bcl-2 and p53, which play a role in determining tumor growth by their effects on apoptosis and cell proliferation respectively, may serve to delineate this subset more accurately. The purpose of this study was to determine the prognostic value of bcl-2, Bax, and mutant p53 in stage I breast cancer. STUDY DESIGN: A total of 75 patients with stage Ic breast carcinoma diagnosed from 1989 to 1992 were identified retrospectively and clinicopathologic parameters such as age, tumor size, estrogen receptor (ER) and progesterone receptor (PR) status, disease-free survival and overall survival obtained. Paraffin-embedded formalin-fixed tissues were immunostained with bcl-2, Bax and p53 monoclonal antibodies using a standard avidin biotin peroxidase reaction. Stained slides were evaluated by two independent pathologists for staining intensity and percentage of cells staining positively. Cox regression was used for multivariate survival analysis using the clinicopathologic parameters and molecular markers. Chi-square tests were used for frequency tables. RESULTS: Mean patient age was 58 years (range 29 to 79 years) with a median followup of 80 months from time of diagnosis. The most common histopathology was infiltrating ductal carcinoma. Neither bcl-2 nor Bax expression was associated statistically with disease-free or overall survival. Expression of mutant p53 was associated with a significant decrease in both 5-year disease-free survival (70% versus 98%, p 相似文献   

Elevated Levels of Apoptosis Regulator Proteins P53 and BCL-2 are Independent Prognostic Biomarkers in Surgically Treated Clinically Localized Prostate Cancer

Purpose

The tumor suppressor gene (TSG) p53 and the proto-oncogene bcl-2 have been shown to be involved in the regulation of cell growth and apoptosis and have been implicated in hormone refractory prostate cancer (PC) and poor prognosis. The goal of this study was to determine the clinical utility of the presence of p53 and bcl-2 immunohistochemical (IHC) protein in the primary tumor as predictors of disease progression following radical prostatectomy (RP).

Materials and Methods

The expression of p53 and bcl-2 was evaluated in archival paraffin-embedded RP specimens from 175 patients followed from 1 to 9 years (mean = 4.6 years) and correlated with stage, grade, race and serologic (PSA) recurrence following surgery.

Results

Overexpression of bcl-2 was noted in 47 of 175 (26.9 percent) patients; these patients had a significantly higher 5-year failure rate than those who did not overexpress bcl-2 (67.0 percent versus 30.7 percent). Expression of p53 was noted in 114 of 175 (65.1 percent) patients with a 5-year failure rate of 51.1 percent compared with a 5-year failure rate of only 22 percent in p53 negative patients. When expression rates for p53 and bcl-2 were combined, the 5-year failure rate was 75.3 percent. Conversely, when both p53 and bcl-2 IHC staining were negative, the 5-year failure rate was 20.4 percent. Univariate Kaplan-Meier analysis showed a statistically significant difference between p53 and bcl-2 positive and negative patients (p less than 0.001). Multivariate Cox Regression Analysis with backward elimination controlling for age, race, stage and grade showed both p53 (p = .0185) and bcl-2 (p = .044) to be independent predictors of disease-free survival.

Conclusion

p53 and bcl-2 appear to be important biomarkers that predict recurrence in clinically localized PC after RP.     

Relationship of p53 and bcl-2 to Prognosis in Muscle-Invasive Transitional Cell Carcinoma of the Bladder

Purpose

We examined the presence of the p53 and Bcl-2 oncoproteins, as detected by immunohistochemistry, in muscle-invasive bladder cancer and correlated this with survival.

Materials and Methods

Formalin-fixed cystectomy specimens from 41 consecutive patients with mean follow-up of 52 months were used. Five patients were either lost to follow-up or died of other diseases and were not included in the survival evaluation.

Results

Eighteen of 36 patients died of metastatic transitional cell carcinoma. p53 immunostaining was found in 61 percent of patients. In 21 of 23 this staining was homogeneous, with more than 75 percent of cancer cells staining using a DO-1/DO-7 antibody cocktail. p53 staining was not correlated with stage (p greater than 0.25) or grade (p less than 0.10) in these invasive cancer specimens. Contrary to recent studies p53 immunostaining was not correlated with disease-specific survival. Bcl-2 immunostaining was found in 28 percent of patients and was not correlated with grade (p greater than 0.25) or disease-specific survival. No combination of p53 and Bcl-2 staining gave added predictive information.

Conclusions

Cytoplasmic Bcl-2 is found in a small percentage of these cancers and does not correlate with prognosis. Further, p53 molecular overexpression is detected in the majority of muscle-invasive bladder tumors as a field defect. However, in patients undergoing cystectomy, it does not correlate with prognosis.     

Protein Expression of bax, bcl-2, and p53 in Patients with Non-Hodgkin's Gastric Lymphoma: Prognostic Significance

The biologic significance of bcl-2, bax, and p53 gene expression in patients with non-Hodgkin's gastric lymphoma is unknown. We examined the prognostic value of these genes in 36 patients with gastric lymphoma treated in our clinic between 1990 and 1995. Paraffin-embedded specimens from 36 patients who underwent primary resection of the stomach for gastric lymphoma were analyzed immunohistochemically for p53, bax, and bcl-2 gene expression. Expression of bax was seen in 24 of 36 patients (66.7%), p53 expression was found in 8 of 36 tumors (22.2%), and bcl-2 cytoplasmic staining was detected in 6 of 36 patients (16.7%). We performed a univariate analysis to examine the possible correlation between the expression of these genes and the survival of our patients. Expression of bax protein proved to be a statistically significant prognostic factor (p= 0.049). Protein expression of p53 and bcl-2 did not statistically correlate with survival. In the bcl-2-negative (−) patient group (30 patients), those who were bax-positive had a statistically significant better survival than those who were bax-negative (63.3% vs. 36.7%, p= 0.03). There was also a statistically significant correlation between p53 expression and the grade of the tumor (p= 0.0014). P53 protein expression increased along with the grade. Expression of bax is a significant prognostic factor in patients with gastric lymphoma. Its prognostic value increases significantly when studied in bcl-2-negative patients; but expression of bax failed to be an independent prognostic factor. Expression of bcl-2 and p53 has no prognostic significance. Expression of p53 seems to represent a marker for loss of differentiation.     

MIB-1 Proliferation Index in Ductal Carcinoma In Situ of the Breast: Relationship to the Expression of the Apoptosis-Regulating Proteins bcl-2 and p53

Tumor growth is the net result of cell proliferation and cell death. To investigate the relationship between these phenomena in ductal carcinoma in situ (DCIS), we studied proliferation index (PI) in DCIS in relation to the expression of two proteins involved in the regulation of cell death, bcl-2 and p53. Thirty-nine consecutive cases of DCIS were studied. PI was determined using immunolabeling with the monoclonal antibody MIB-1. The proportion of MIB-1-positive nuclei among 500 tumor cell nuclei was determined for each case and constituted the PI. All cases were also assessed immunohistochemically for bcl-2 and p53 protein expression. DCIS cases were graded using the criteria of Holland et al. PI ranged from 0 to 57% (mean 11.2%, median 4.6%). PI was significantly lower in well-differentiated and intermediately differentiated DCIS cases (mean 7.3% and 4.8%, respectively) than in poorly differentiated lesions (mean 24%, p = 0.01). PI was significantly lower in bcl-2-positive cases than in bcl-2-negative cases (mean PI for bcl-2-positive cases 6% and for bcl-2-negative cases 26%, p = 0.01). PI was higher in lesions expressing the p53 protein than in p53 negative cases (19% versus 8.3%), but this difference did not reach statistical significance. PI was also examined in relation to combinations of bcl-2 and p53 expression. Twenty-five of the DCIS lesions (64%) showed the bcl-2-positive/p53-negative phenotype which is similar to that seen in normal breast tissue and benign lesions and can be considered the "physiologic" combination. Among these cases the mean PI was 6.4%. In contrast, 14 cases showed "aberrant" combinations of bcl-2 and p53 expression suggesting dysregulated control of apoptosis. Among these cases the mean PI was 19.6% (p = 0.03). The highest mean PI was in cases with the bcl-2-negative/p53-positive phenotype (PI = 29.7%). DCIS lesions with the physiologic bcl-2-positive/p53-negative phenotype have low PI. In contrast, DCIS lesions with "aberrant" bcl-2/p53 phenotypes have high PI. This combination may favor tumor growth and progression in DCIS.     

p53 Protein and Gene Alterations in Pathological Stage C Prostate Carcinoma

Purpose

We determined the extent of p53 immunoreactivity in pathological stage C prostate cancer as well as its correlation to tumor grade, substage, recurrence and proliferation rate. To define better the temporal relationship of p53 nuclear reactivity in prostate cancer p53 immunoreactivity was evaluated in all associated prostatic intraepithelial neoplasia lesions.

Materials and Methods

Using immunohistochemistry p53 status and proliferation rate were determined in 96 tumors from patients with pathological stage C prostate cancer. Single strand conformational polymorphism in exons 5 to 8 was used in a subset of specimens to assess the association of p53 nuclear accumulation with mutations in the p53 gene.

Results

p53 Nuclear reactivity was demonstrated in 10 tumors (10.4%), including 6 with high and 4 with low level nuclear reactivity. Of the tumors 86 (89.6%) had no evidence of p53 immunoreactivity. Each of the 6 tumors with high level p53 reactivity had associated areas of prostatic intraepithelial neoplasia that also showed p53 nuclear reactivity. Furthermore, pathological stage C substage (C1, 2 or 3) was significantly associated with p53 nuclear reactivity (p = 0.04). Proliferation rates were correlated with p53 nuclear reactivity (p = 0.09), while there was no association with tumor grade or recurrence. p53 Gene alterations were noted in 2 of the 3 p53 positive tumors versus no alterations in the p53 gene of 3 p53 negative tumors.

Conclusions

p53 Nuclear accumulation is uncommon in pathological stage C prostate cancer and its presence in premalignant prostatic intraepithelial neoplasia lesions suggests that it may be an early event in a subset of prostate cancers.     

Prognostic Factors Including Proliferation Markers Ki-67, bax, and bcl-2 in Temporal Bone Paraganglioma

Valuable criteria with which to predict the clinical behavior of the temporal bone paraganglioma or the response to treatment are lacking. The analysis of markers of cell proliferation is a possibility to estimate the prognosis. Extensive patient data on 40 temporal bone paragangliomas were gathered over the years and correlated with the data obtained by staining histologic sections with bcl-2, bax, and MIB I markers of cellular proliferation. The immunohistochemistry was in all cases negative for bcl-2, positive for bax, and for Ki-67 positive in 20% of tumors. The scores for Ki-67 did not correlate with the majority of clinical parameters, except for treatment modality, preoperative hearing loss, and cranial nerve involvement. The tendency toward poorer hearing and a higher incidence of preoperative lower cranial nerve palsies was demonstrated in patients with higher Ki-67 scores. Furthermore, the higher rate of subtotal tumor removals in these patients reveals technical difficulties in accomplishing a radical removal, although the incidence of residual tumors was thus not affected. In view of the present information obtained with proliferation markers, the site of tumor origin still remains the most predictive variable for the course of the disease.     

Prognostic Factors Including Proliferation Markers Ki-67, bax, and bcl-2 in Temporal Bone Paraganglioma

Valuable criteria with which to predict the clinical behavior of the temporal bone paraganglioma or the response to treatment are lacking. The analysis of markers of cell proliferation is a possibility to estimate the prognosis. Extensive patient data on 40 temporal bone paragangliomas were gathered over the years and correlated with the data obtained by staining histologic sections with bcl-2, bax, and MIB I markers of cellular proliferation. The immunohistochemistry was in all cases negative for bcl-2, positive for bax, and for Ki-67 positive in 20% of tumors. The scores for Ki-67 did not correlate with the majority of clinical parameters, except for treatment modality, preoperative hearing loss, and cranial nerve involvement. The tendency toward poorer hearing and a higher incidence of preoperative lower cranial nerve palsies was demonstrated in patients with higher Ki-67 scores. Furthermore, the higher rate of subtotal tumor removals in these patients reveals technical difficulties in accomplishing a radical removal, although the incidence of residual tumors was thus not affected. In view of the present information obtained with proliferation markers, the site of tumor origin still remains the most predictive variable for the course of the disease.     

Prognostic Significance of Regulators of Cell Cycle and Apoptosis, p16INK4a, p53, and bcl-2 in Primary Mucosal Melanomas of the Head and Neck

Abnormalities in cell cycle regulation, tumor suppressor gene functions and apoptosis are frequent events in tumorigenesis. Their role in the pathogenesis and prognosis of primary mucosal melanomas (MM) of the upper aerodigestive tract remains unknown. Sixty-four patients (40 men, 24 women, median age 64 years) with MM were included in this study; 32 had tumors in the nasal/paranasal cavities, 28 in the oral cavity and 4 in the pharynx. Archival tissues from 47 initial mucosal tumors, 17 mucosal recurrences, and 13 nodal/distant metastases were subjected to immunohistochemistry using antibodies against p16, p53, and bcl-2. The results were correlated with histological features and survival data. Expressions of p16, p53, and bcl-2 proteins were seen in 25% (N=19/76), 21% (N=16/76), and 74% (N=56/76) of all tumors, respectively. bcl-2 expression in the initial tumors was associated with significantly longer overall and disease specific survival (3.3 vs. 1.5 years, P ≤ 0.05). Expression of p16 was increasingly lost, from 32% in initial tumors to 12% in recurrent and 15% in metastatic tumors (P=0.06). Tumors comprised of undifferentiated cells were significantly more p53 positive than epithelioid or spindle cells (80% vs. 33%, P=0.02). Expression of these markers did not correlate with necrosis, or vascular and/or deep tissue invasion. Expression of bcl-2 is associated with better survival in MM. Loss of p16 was seen with tumor progression whereas aberrant p53 expression was frequent in undifferentiated tumor cells.     

前列腺癌组织中p53、bcl-2和E-cadherin蛋白的表达水平及临床意义

目的探讨不同前列腺组织中p53、bcl-2和E-cadherin蛋白的表达水平及临床意义。方法收集活检或手术切除的人前列腺组织标本,按病理诊断分为前列腺癌组46例、前列腺增生组25例;其中前列腺癌组又分为高分化组(11例)、中分化组(13例)、低分化组(22例)。应用免疫组织化学SP法检测上述标本中p53、bcl-2和E-cadherin蛋白的表达情况。结果前列腺癌组织中p53和bcl-2的阳性表达率(50.0%和58.7%)显著高于前列腺增生组织的p53和bcl-2的阳性表达率(12.0%和8.0%),差异具有统计学意义(P0.05)。bcl-2在前列腺癌高分化组的阳性表达率(36.4%)显著低于低分化组(72.7%)(P0.05)。前列腺增生组织中E-cadherin蛋白表达阳性表达率为100.0%,前列腺癌组织中阳性表达率为43.5%,两组E-cadherin蛋白表达阳性率相比较,差异具有统计学意义(P0.05)。E-cadherin蛋白在前列腺癌高、中、低分化3组中的阳性表达率分别为90.9%、46.2%、18.2%,高分化组阳性表达率显著高于低分化组,差异具有统计学意义(P0.05)。结论 p53、bcl-2和E-cadherin蛋白的异常表达与前列腺癌的发生发展密切相关,检测p53、bcl-2和E-cadherin蛋白表达水平对前列腺癌鉴别诊断及临床预后具有重要价值。     

Prognostic Significance of p53 and Ki67 Proteins Expression in Greek Gastric Cancer Patients

Aim: The variability of prognosis of gastric cancer (GC) within a pathological stage necessitates the identification of subgroups of patients with a more aggressive disease. The role of p53 and Ki67 expression in gastric carcinoma is far from being fully established. The aim of the present study was to evaluate the expression of p53 and Ki67 in gastric cancer and correlate the findings with several clinicopathological features and prognosis. Materials and methods: Tissue samples from 93 patients treated by gastric resection for gastric carcinoma between 1996 and 2001 were used. Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53 and Ki67. The results were correlated with clinicopathological features and survival. Results: Stronger expression of p53 was related with tumor size greater than 5 cm and advanced stage. Stronger expression of Ki67 correlated with higher ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (metastatic lymph node [MLN] ratio) and advanced stage. Moreover, p53 and Ki67 overexpression, tumor size greater than 5 cm, MLN ratio, depth of invasion, lymph node metastasis, stage III and IV and infiltrative macroscopic appearance were adverse prognostic factors. The levels of p53 and Ki67, the MLN ratio, the tumor size (above 5 cm) and the stage of the disease were identified as independent prognostic factors of survival.

Conclusions: In gastric cancer, the expression of p53 and Ki67 provides significant information about prognosis. The routine evaluation of p53 and Ki67 levels could be a useful tool in identification of patient with more aggressive disease and contribute to a better therapeutic approach.     

Comparison of p53 and bcl-2 expression in initial, synchronous, and metachronous colorectal adenomas

To investigate the significance of p53 and bcl-2 expression in metachronous colorectal adenomas arising in the remaining colon after carcinoma resection, we analyzed p53 and bcl-2 expression immunohistochemically in initial adenomas (type I), synchronous adenomas with concurrent carcinoma (type II), and metachronous adenomas arising after resection of initial adenomas (type III) or carcinoma (type IV). The incidence of p53 immunoreactivity in type IV adenomas with mild dysplasia was significantly higher than that in type I, type II, or type III adenomas with mild dysplasia. bcl-2 immunoreactivity was more frequently detected in type IV adenomas with mild dysplasia than in type I or type III adenomas with mild dysplasia. Coexpression of p53 and bcl-2 was detected in 16% of the type IV adenomas, this being a significantly higher frequency than that seen in the type I, type II, or type III adenomas. These results suggest that the evaluation of p53 and bcl-2 in metachronous adenomas in the remaining colon after resection of carcinoma may be a useful biologic marker for assessing the risk of cancer development. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Science, and Culture of Japan     

p53 and bcl-2 immunohistochemistry in preoperative biopsies as predictors of biochemical recurrence after radical prostatectomy

OBJECTIVE: To evaluate p53 and bcl-2 immunohistochemistry in preoperative biopsies and radical prostatectomy specimens, as predictors of biochemical recurrence. PATIENTS AND METHODS: Preoperative biopsies from 73 men, and the radical prostatectomies from these men and from a further 47 men, were evaluated. The serum prostate specific antigen (PSA) level, Gleason score, pathological stage and margin involvement were recorded. The immunohistochemical expression of p53 and bcl-2 was studied on a representative area of tumour with the highest Gleason grade. The median follow-up was 53 months. RESULTS: During the follow-up 47 of the 120 patients had a biochemical recurrence. Capsular penetration was present in 63 (53%) and the surgical margins were positive in 47 (39%). The Gleason score was < 7 in 81 (68%) patients; p53 was positive in 40 (66%) of 61 biopsies and 84 (71%) of 118 prostatectomy specimens. Bcl-2 was positive in eight (13%) of 63 biopsies and 20 (17%) of 118 prostatectomies. On multivariate analysis the biopsy p53, Gleason score and serum PSA were significant predictors of recurrence. On multivariate analysis, capsular penetration, PSA and margin status at prostatectomy were significant predictors of recurrence. There was also a significant interaction between PSA and margin status. Although univariately significant, neither p53 nor bcl-2 featured in the final multivariate model. CONCLUSION: Biopsy p53 status significantly predicts recurrence after radical prostatectomy, but its low specificity and technical issues suggest that it will not be useful in the clinical setting. However, a patient with negative p53 on biopsy is likely to have a good prognosis on prolonged follow-up.     

Preoperative p53, bcl-2, CD44 and E-cadherin immunohistochemistry as predictors of biochemical relapse after radical prostatectomy

PURPOSE: Since radical prostatectomy is performed to cure prostate cancer, identification of markers enabling preoperative prediction of relapse after radical prostatectomy is essential to counsel and select patients for adjuvant therapy. Aberrant p53, bcl-2, CD44 and E-cadherin immunohistochemistry has been associated with aggressiveness in prostate cancer. We assessed these biomarkers in biopsy and radical prostatectomy specimens as predictors of biochemical relapse. MATERIALS AND METHODS: A total of 76 patients with untreated clinically localized prostatic adenocarcinoma underwent radical prostatectomy. Preoperative (prostate specific antigen, biopsy Gleason score) and postoperative (pathological stage and margin status) variables, biopsy and radical prostatectomy biomarker immunohistochemistry were correlated with relapse. Univariate and multivariate statistical analyses identified significant predictors. RESULTS: Of the 76 patients 23 (30%) had relapse (mean followup 38 months). Aberrant p53, bcl-2, CD44 and E-cadherin expression was observed in 64, 12, 85 and 12% of biopsies and 57, 20, 64 and 49% of radical prostatectomy specimens, respectively. Biopsy Gleason 7 to 10 and biopsy p53, respectively, gave the highest positive and negative predictive values for relapse. Relapse occurred in 13% of patients with normal biopsy p53 and in half with aberrant p53. Multivariate analysis revealed Gleason score and p53 to be independent preoperative predictors (p = 0.01 and 0.02, respectively). Estimated risk of relapse was 3.5 times higher in patients with Gleason scores 7 to 10 and 24% higher in those with aberrant p53. Significant postoperative predictors were bcl-2, p53, Gleason score and margin status (p = 0.01, 0.01, 0.04 and 0.01, respectively). CONCLUSIONS: Aberrant biopsy p53 is associated with a significantly worse outcome after radical prostatectomy than normal p53, highlighting a potential clinical role for p53. Postoperative p53 and bcl-2 were significant predictors of outcome after radical prostatectomy.     

The Prognostic Importance of E-cadherin and p53 Gene Expression in Transitional Bladder Carcinoma Patients

Objective: The clinical course of transitional cell carcinoma is highly variable. The determination of sensitive prognostic factors for transitional cell carcinoma is very important. Therefore e-cadherin and p53 immunohistochemical activity can be used with other prognostic factors. Methods: The study comprised with 61 (4 women and 57 men) selected patients who had transitional cell carcinoma. Paraffin embedded tissue sections were investigated immunohistochemically for e-cadherin normal staining and p53 over expression. Results: It is seen that when grade and stages of illness increased normal staining of e-cadherin decreased and p53 over expressed. Abnormal e-cadherin was significantly associated with disease recurrence (P < 0.001), disease progression (P < 0.001) and bladder specific survival. p53 differentiation was not significant for disease recurrence (P > 0.05) inverse to prognosis of illness. Transurethral resectomy and BCG treatments were not effected e-cadherin and p53 activity within the groups statistically. Conclusion: Significant differences can be helpful to investigate patients more detailed pathologically. These expression rates in different type of transitional cell carcinoma patients may represent a biologically more aggressive cancer, requiring early definitive therapy. This hypothesis should be evaluated in larger studies and prospective clinical trials.     

Nuclear p53 Overexpression in Bladder, Prostate, and Renal Carcinomas

Background :
The aim of this study was to examine nuclear p53 overexpression in transitional cell carcinoma of the bladder, adenocarcinoma of the prostate, and renal cell carcinoma.
Methods :
Forty-four pathologic specimens from 39 bladder cancer patients, 41 prostatic adenocarcinoma, and 39 renal cell carcinoma specimens were analyzed immunohistochemically with D07 monoclonal antibody to detect the expression of the mutant p53 gene. Overexpression was said to occur when the number of positively-stained tumor nuclei were≥ 10% in each specimen. p53 overexpression was correlated with the clinical and histopathological features of these cancers.
Results :
Nuclear p53 overexpression occurred in 18.2% of transitional cell bladder cancer specimens, 12.2% of prostate cancer specimens, and 17.9% of renal cell cancer specimens. Statistical analyses showed that grade, vascular invasion, and necrosis in bladder cancer, a high Gleason score in prostate cancer, and the 1-year mortality rate in renal cancer were significantly related with p53 nuclear overexpression (P<0.05).
Conclusion :
Using the D07 monoclonal antibody, nuclear p53 overexpression is relatively uncommon in urologic malignancies, and moderately correlates with several histopathological and clinical features of urologic malignancies.     

Expression of bcl-2, p53 oncoprotein, and proliferating cell nuclear antigen in renal cell carcinoma

OBJECTIVES: This study was designed to examine the immunohistochemical expression of bcl-2, p53, and proliferating cell nuclear antigen (PCNA) and the relation of this expression to clinicopathological characteristics and prognosis in renal cell carcinoma (RCC). METHODS: The expression of bcl-2, p53 protein, and PCNA was studied by immunohistochemical methods in paraffin-embedded nephrectomy specimens from 53 patients whose clinicopathological data had already become clear. RESULTS: The expression of the bcl-2 protein was recognized in 34 cases (64%); the expression of the p53 protein, however, was seen in only 1 case. Bcl-2 positivity was not associated with any pathological parameters or prognosis. If the percentage of PCNA-positive cancer cells as compared to the total amount of cancer cells was defined as a labeling index (LI), a high PCNA LI number correlated significantly with a high T category, high grade, venous invasion, and shortened survival. Among the conventional pathological parameters, the T category, nuclear grade, and venous invasion had the most significant effect on prognosis. A multivariate analysis in the parameters of PCNA, T category, nuclear grade, and venous invasion demonstrated that only nuclear grade had a significant effect on prognosis. CONCLUSIONS: The inhibitory effect of the bcl-2 gene on apoptosis related to tumor development is not clear, and the expression of the p53 protein is uncommon in RCC. PCNA seems to be a good objective and quantitative marker of the biological malignant potential in RCC, although the assessment of malignant potential in combination with conventional pathological parameters is indispensable.     

小鼠乳腺癌中p53与bcl-2/bax基因表达的相关性研究

目的探讨p53基因和bcl-2/bax基因在乳腺癌发病机制中的作用以及它们之间的相互关系。方法以小鼠乳腺癌BCML-TA299可移植模型为研究对象,用免疫组织化学染色法观测α-干扰素(INF-α)干扰后p53基因与bcl-2/bax表达的关系。结果实验性乳腺癌BCML-TA299治疗组荷瘤鼠生存期较对照组延长,且随着时间的推延治疗组肿瘤的体积明显低于对照组的肿瘤体积;治疗组与对照组比较,肺转移率低。对照组p53蛋白阳性表达率为92.01±0.48,而治疗组中p53呈阴性表达。对照组瘤组织bcl-2蛋白表达为50.21±0.52,bax蛋白表达为12.08±0.13;治疗组瘤组织bcl-2蛋白表达为12.01±0.2,bax蛋白表达为48.19±0.57。对照组p53蛋白表达与bcl- 2呈正相关,而与bax呈负相关(P<0.05);治疗组中p53呈阴性表达,bcl-2和bax表达与对照组结果相反。结论bcl-2和bax的表达受p53调节。p53、bcl-2/bax在乳腺癌发病机制中起着较重要的作用。