Association of positive serum anti-p53 antibodies with poor prognosis in bladder cancer patients

AIMS: To assess the association of serum anti-p53 antibodies and overexpression of tumor p53 protein with survival and prognostic factors in patients with urinary bladder tumors. METHODS: Seventy-six patients with transitional cell carcinoma of the urinary bladder were assessed prospectively (Ta, 18; T(1), 30; > or =T(2), 28). Serum anti-p53 antibodies were detected by enzyme-linked immunosorbent assay. Tumor p53 gene overexpression was assessed by immunohistochemical staining. The mean follow-up time was 34 months. RESULTS: Serum anti-p53 antibodies were positive in 25 patients (33%). Overexpression of tumor p53 protein was positive in 41 patients (54%). There was an association between the presence of serum anti-p53 antibodies and tumor p53 gene overexpression (P = 0.001). The total survival of the patients with positive serum anti-p53 antibodies was shorter than the patients with positive tumor p53 gene overexpression (P < 0.001, P = 0.344, respectively). In the multivariate survival analysis, both tumor stage and serum-p53 antibodies were found to be independent survival predictors (P = 0.004, P = 0.006, respectively). CONCLUSION: Serum anti-p53 antibody positive tumors had a worse prognosis than those with negative serum levels, regardless of the p53 status of the tumor.     

Serum anti-p53 antibodies and p53 protein status in the sera and tumors from bladder cancer patients

OBJECTIVES: The purpose of this study was to evaluate the association between the serum anti-p53 antibodies (Abs) status and the p53 protein status in the sera and tumors as well as clinical or pathological parameters in bladder cancer patients retrospectively. METHODS: Serum samples from 100 patients with bladder cancer were assayed for anti-p53 Abs and p53 protein by enzyme-linked immunosorbent assay (ELISA). A monoclonal antibody DO7 was used for immunohistochemical staining of tumor p53 protein. RESULTS: Prevalences of serum anti-p53 Abs, serum p53 protein and tumor p53 protein were 12, 1 and 63%, respectively. There was a significant correlation between serum anti-p53 Abs status and factors including tumor stage, tumor grade, and tumor p53 protein status. In the univariate analysis, tumor stage, tumor grade, serum anti-p53 Abs status, and tumor p53 protein status were significantly associated with an increased risk of death. Multivariate analysis showed that tumor stage was the only independent prognostic factor among the factors examined. CONCLUSIONS: The present study suggests that serum anti-p53 Abs had a limited value as a tumor marker in bladder cancer patients. Further studies to elucidate the mechanism of anti-p53 Abs production will be necessary for a better understanding of the immune status in bladder cancer patients.     

Importance of serum p53 antibodies during follow-up after treatment of invasive bladder tumors

INTRODUCTION: To investigate the prognostic importance of the changes in serum p53 antibody titrations during follow-up of patients who had anti-p53 antibody-positive invasive bladder tumors with transitional epithelial cells. MATERIALS AND METHODS: The study group consisted of 23 clinically T3相似文献   

p53 and microvessel density in primary resection specimens of superficial bladder cancer

PURPOSE: p53 Regulates angiogenesis in fibrosarcoma and correlative studies suggest a similar role for muscle invasive bladder cancer. We evaluated the associations of p53 status and microvessel density with pathological features and clinical outcomes in a large population of patients with superficial bladder cancer. In addition, we assessed the correlation of p53 status with microvessel density, which would suggest the regulation of angiogenesis by p53. MATERIALS AND METHODS: We stained 84 primary bladder resection specimens, including 55 stage pTa, 29 stage pT1, 27 grade 1, 35 grade 2 and 22 grade 3 samples, for p53, CD31 and CD34. The relationships of p53 or microvessel density and tumor stage-grade or clinical recurrence-progression were analyzed by analysis of variance and pairwise comparison analysis for least significant difference, and Pearson correlation coefficients. Only patients with no previous biopsy were included in analysis to preclude interference by granulation tissue related neovascularization. The 4 samples with significant inflammation were also excluded from study. RESULTS: At a mean followup of 33 months (range 1 to 93) 34 of 84 patients (40.4%) experienced 1 or more tumor recurrences and 10 (11.9%) had stage and/or grade progression. Statistically significant associations were observed of p53 immunostaining and microvessel density with tumor stage and grade (p <0.05). However, the association of p53 status with microvessel density was weak and not statistically significant. Similar results were observed for the CD31 and CD34 based estimates of microvessel density. Neither p53 status nor microvessel density correlated with recurrence or progression. CONCLUSIONS: Our study confirms the strong association of p53 and microvessel density with the well established prognostic factors of grade and stage in superficial bladder cancer, supporting other evidence of an important role for p53 and angiogenesis in the tumor biology of this disease. However, our data argue against a primary role of p53 in the regulation of angiogenesis in superficial bladder cancer. This study, which to our knowledge is the first to focus on primary resection specimens, suggests that other genetic or environmental factors may contribute to the regulation of angiogenesis in superficial bladder cancer.     

Serum p53 and bladder cancer: can serum p53 be used as a tumor marker?

The aim of this study was to find the correlation between serum p53 and carcinoma of the bladder and to investigate whether serum p53 protein can be used as a tumor marker for p53 gene alteration. The study included patients with carcinoma of the bladder and controls. Serum p53 protein estimation was done with an ELISA kit. There were 23 patients with superficial and 17 with invasive carcinoma. The median serum p53 was 31.5 U/ml in superficial and 41 U/ml in invasive cancer. This was significantly higher than the mean value (16.4 U/ml) of controls. Serum p53 rises in patients with carcinoma of the bladder and correlates with the grade of the disease .It can therefore be used as a tumor marker for bladder cancer.     

Prognostic significance of serum p53 protein and p53 antibody in patients with surgical treatment for head and neck squamous cell carcinoma

OBJECTIVES: This study aims at investigating the prognostic values of serum p53 protein and anti-p53 antibody in patients undergoing surgical treatment for head and neck squamous cell carcinoma (HNSCC). METHODS: Serum p53 protein and anti-p53 antibody concentrations were determined by an enzyme-linked immunosorbent assay (ELISA) in 75 patients with HNSCC and 28 healthy controls. In 28 patients, formalin-fixed tumor tissues were also available for immunohistochemical staining by an anti-p53 DO7 monoclonal antibody. The results were correlated with the clinicopathologic parameters. RESULTS: The mean preoperative serum concentration of p53 protein in patients with HNSCC was significantly higher than healthy controls (59.45 pg/mL vs 16.4 pg/mL, p =.007). Preoperative serum p53 antibody was present in 23 (31%) patients and was present in one healthy control. Eighteen (62%) tumor tissues showed p53 overexpression by immunohistochemistry. The presence of serum anti-p53 antibody before operation was associated with a significantly higher incidence (65%) of nodal metastasis compared with 27% nodal metastasis in patients with absence of serum anti-p53 antibody (p =.002). CONCLUSION: Preoperative serum p53 antibody was a significant prognostic factor for nodal metastasis of HNSCC.     

The correlation of p53 protein overexpression and p53 antibodies in serum of patients with transitional cell carcinoma of the urinary bladder

BACKGROUND: Mutations of p53 gene were demonstrated in many solid tumors with varying frequency. We analyzed the relationship between p53 protein expression in bladder cancer tissue, p53 autoantibodies in serum and the clinical course of 32 patients with and 10 patients without transitional cell carcinoma of the urinary bladder. MATERIALS AND METHODS: In the 32 patients studied, bladder cancer was diagnosed as pTaG1-2 in 8 cases, pT1G2 in 6, pT1G3 in 7, pT2G2-3 in 7, pT3G2-3 in 3 and pT4 in 1 patient. Anti-p53 antibodies were detected by an enzyme-linked immunosorbent assay. Immunohistochemical staining was performed using a standardized alkaline phosphatase monoclonal anti-alkaline phosphatase method. To prove the statistical significance of tumor grading and staging, the Kruskal-Wallis test was applied (p < 0.01). The mean follow-up was 26 months. RESULTS: We found 12.5% p53 autoantibody-positive sera without a statistically significant correlation with tumor grade (p = 0.0569) and category (p = 0.612). Three of 4 patients who had p53 autoantibody-positive sera died within 9 months. All of these sera-positive patients had p53 protein-positive tumor tissue. Control sera were all negative for p53 autoantibodies. CONCLUSION: This study shows a strong relationship between p53 protein overexpression and the occurrence of p53 autoantibody in bladder cancer. The expression of p53 autoantibodies seems to be an event in cases of bladder cancer with an unfavorable tumor-specific outcome. Because of the small number of cases and the short follow-up time, further quantitative studies will hopefully demonstrate whether this might be of prognostic importance.     

CORRELATION OF p53 PROTEIN EXPRESSION IN HUMAN UROTHELIAL TRANSITIONAL CELL CANCERS WITH MALIGNANT POTENTIAL AND PATIENT SURVIVAL

The p53 gene product has been detected frequently in various human malignancies. We have studied the expression of p53 protein in urothelial transitional cell cancers (TCCs) and examined its correlation with pathologic grade, stage(pT) and patient survival. Specimens from 69 surgically-resected TCCs (38 cases of urinary bladder cancer, 17 cases of ureteral cancer and 14 cases of renal pelvic cancer) were examined by immunohistochemical staining, using two anti-p53 monoclonal antibodies, PAb1801 and PAb240, and a polyclonal antibody, CM-1. Twenty-six TCCs (37.6%) were positively stained by at least one of the three antibodies. Statistical analysis showed a significant correlation between p53 expression and high pathologic grade (p less than 0.05, p less than 0.001) or progressive pathologic stage (p less than 0.01). In addition, in 51 of the patients who were available for follow-up (23 cases of urinary bladder cancer, 13 cases of ureteral cancer, and 15 cases of renal pelvic cancer), the correlation between p53 protein expression and prognosis was examined. The survival of patients exhibiting positive p53 protein expression was significantly worse than those with p53-negative tumors (p less than 0.05). These results suggest that an immunohistochemical test for p53 protein may be a useful method of evaluating the malignant potential of TCCs. Additionally, expression of p53 protein in TCCs is an indicator of a poor prognosis which should be considered in drawing up treatment strategies.     

Serum p53 antibody is a useful tumor marker of early colorectal cancer

The aim of this study was to evaluate the significance of preoperative serum p53 antibodies (Abs) in patients with colorectal cancer. Between 2007 and 2008, serum p53 Abs were measured by enzyme-linked immunoabsorbent assay in 100 consecutive patients with colorectal cancer. Relationships between clinicopathologic features and the preoperative presence of serum p53 Abs were evaluated. Serum p53 Abs were positive in approximately 30%, regardless of the depth of tumor invasion--sm (submucosa), mp (muscularis propria), or ss (subserosa). Two patients among 23 T1 patients (9%) had lymph node metastasis. These 2 patients belonged to a group of 7 patients who were determined positive for serum p53 Abs (29%), although none of 16 patients negative for serum p53 Abs had lymph node metastasis, regardless of vascular invasion. Preoperative serum p53 Abs do not seem to be a marker of tumor progression but may be a useful marker for detecting high risk of lymph node metastasis in T1 colorectal cancer.     

肿瘤组织VEGF表达和MVD与膀胱癌预后的关系

目的:探讨肿瘤组织中血管内皮生长因子(Vascular endothelial growth factor,VEGF)表达和微血管密度(Microvessel density,MVD)与膀胱癌预后的关系。方法:采用免疫组织化学方法检测62例膀胱癌手术标本中VEGF和MVD。结果:VEGF阳性表达率为63%,VEGF阳性表达的肿瘤组织中的MVD明显高于阴性者(P<0.01);VEGF表达和MVD与肿瘤的浸润生长、血行转移、淋巴结转移具有明显相关关系(P<0.05,P<0.01);VEGF阳性表达者的预后较阴性者差;多因素分析表明,VEGF和MVD可能成为判断膀胱癌预后的新因素。结论:VEGF表达和MVD与膀胱癌的恶性进程和不良预后有关,测定VEGF和MVD可能是判断膀胱癌预后有价值的指标。     

p53 antibodies in the serum of patients with prostate cancer

We assessed the potential clinical utility of levels of p53-specific antibodies as a novel serum biomarker of prostate cancer that could be used in conjunction with level of PSA. Material and methods Serum levels of p53-specific antibodies in patients with relapsed, newly diagnosed prostate cancer and in patients with benign prostate hyperplasia were quantified by an enzyme-linked immunoabsorbent assay. Result There was no significant difference (P = 0.96) between the serum levels of p53-specific antibodies in patients with newly diagnosed prostate cancer and with benign prostatic hyperplasia. In the newly diagnosed prostate cancer group, stage T1c (n = 8) showed the lowest p53-specific antibody level. However, the difference between T1c group and benign prostatic hyperplasia group was not significant (P = 0.686). The relapsed cancer group tended to have low levels of the antibodies, and, there was no significant difference between the relapsed prostate cancer group and the benign prostatic hyperplasia group (P = 0.14). The serum levels of p53-specific antibodies in patients with metastatic and with localized prostate cancer showed no significant difference (P = 0.68). Conclusion The use of titers of p53-specific antibodies to make differential diagnosis between prostate cancer and benign prostatic hyperplasia might have no role, and the antibodies should not be used as a marker of prostate cancer by itself. Because our study is based on small number of patients, further studies are necessary before its absolute validity can be determined.     

Prognostic significance of angiogenesis in superficial bladder cancer

OBJECTIVE: To assess the prognostic significance of angiogenesis parameters such as microvessel density (MVD) and vascular endothelial growth factor (VEGF) in superficial bladder cancer. PATIENTS AND METHODS: We studied 127 superficial bladder cancer samples immunohistochemically for the above factors. We compared them with standard clinicopathological features (grade, stage, concurrent in situ, multifocality, primary or recurrent status) as well as with p53 expression, recurrence and progression to muscle infiltrating disease. RESULTS: During a 36 months median follow up of 109 patients with superficial primary tumors (min. 3, max. 69 months), 80 of them recurred (73.4%), while 8 patients (7.3%) progressed to muscle invading disease. A significant correlation was noted between MVD and VEGF in all 127 samples (p = 0.019). No association was noted between MVD or VEGF with the other clinicopathological features, recurrence or progression. Although progression free survival rates of categorized microvessel density (up to and higher than median value) differed significantly only in grade 3 patients, no independent prognostic significance could be attributed to MVD. No correlation was observed between MVD or VEGF with p53 protein. CONCLUSIONS: Based on our data we suggest that VEGF is not useful for predicting recurrence or progression in superficial bladder cancer. Microvessel density determination may help to predict progression of grade 3 patients to muscle invasive disease but not as an independent prognostic factor.     

Clinical usefulness of serum antip53 antibodies for prostate cancer detection: a comparative study with prostate specific antigen parameters

PURPOSE: Alterations in the p53 tumor suppressor gene located on human chromosome 17p13.1 are currently the most common genetic abnormalities associated with many different types of human malignancies. Recently serum p53 antibodies (p53-Abs) have been detected in the serum of patients with various cancers. To evaluate the clinical usefulness of serum p53-Abs we compared p53-Abs with prostate specific antigen (PSA) parameters in patients with benign prostatic disease (BPD) and prostate cancer. MATERIALS AND METHODS: Serum samples were obtained from 50 patients with BPD and 103 with histologically diagnosed prostate cancer, including T1c/2N0M0 in 50, T3N0M0 in 29 and TxNxM1 in 24. The serum p53-Abs titer was assessed by enzyme-linked immunoabsorbent assay using a MESCUP Kit II (Medical and Biological Laboratories Co., Ltd., Nagoya, Japan) antip53 test. Free and total PSA was measured using an Architect (Dinabott, Chicago, Illinois) PSA kit. The clinical values of p53-Abs were compared with total PSA, PSA density (PSAD), PSA density of the transition zone (PSATZD) and the free-to-total PSA ratio using ROC curves. RESULTS: All patients with prostate cancer had significantly higher total PSA, PSAD, PSATZD and p53-Abs than patients with BPD. While total PSA, PSAD, PSATZD and free-to-total PSA ratios were associated with stage progression, serum p53-Abs were not related to clinical stage. The Gleason sum 5 or less group had a higher level of p53-Abs than higher Gleason sum groups. Patients with T1c cancer had significantly higher p53-Abs than those with BPD. According to ROC curve analysis to distinguish prostate cancer from BPD the p53-Abs titer had the greatest AUC in the overall patient population and in patients without digital rectal examination findings. CONCLUSIONS: These results suggest that p53-Abs might be helpful in the clinical decision to perform prostate biopsy. In the current study the serum p53-Abs titer had the most useful validity in discriminating between prostate cancer and BPD in the overall patient population and in patients with normal digital rectal examination.     

Presence of serum p53 antibodies is associated with decreased in vitro chemosensitivity in patients with esophageal cancer

Resistance to chemotherapy remains a serious problem inhibiting the successful treatment of advanced esophageal cancer. A number of studies have revealed that p53 genetic alteration and protein overexpression can predict chemosensitivity. Furthermore, p53 protein overexpression in cancer tissues has been found to induce serum p53 antibodies (p53-Abs). This study was conducted to examine whether analysis of serum p53 Abs could predict the chemosensitivity of esophageal cancer. Serum analysis of p53 antibodies was performed by enzyme-linked immunosorbent assay in 19 patients with esophageal squamous cell carcinoma preoperatively, then surgically resected specimens were stained immunohistochemically for p53 protein expression. Tumor tissues were also analyzed for chemosensitivity by the histoculture drug response assay (HDRA) using cis-dichlorodiammineplatinum(II) (CDDP), 5-fluorouracil (5-FU), and adriamycin (ADM). Serum p53-Abs were present in 47% (9/19) of the patients and immunohistochemical analysis revealed overexpression of p53 protein in 42% (8/19) of the tumors. The presence of serum p53 antibodies was significantly correlated with p53 immunoreactivity (P = 0.005). The inhibition index of patients positive for p53-Abs was significantly lower than that of patients negative for p53-Abs (P < 0.001). This tendency was also observed in the inhibition index to 5-FU. The presence of serum p53-Abs was associated with decreased in vitro chemosensitivity to CDDP and 5-FU. Thus, the detection of serum p53-Abs is suggested to be useful for predicting chemosensitivity in patients with esophageal cancer. Received: August 2, 2000 / Accepted: March 6, 2001     

Clinical evaluation of serum p53 antibodies in patients with upper urinary tract tumors

PURPOSE: We retrospectively assessed the clinical significance of anti-p53 antibody (S-p53Ab) status in the serum of patients with upper urinary tract tumors. MATERIALS AND METHODS: Enzyme-linked immunosorbent assay was used to analyze S-p53Abs in 63 upper urinary tract tumors. Its incidence and clinical or pathological background were analyzed in comparison with 80 bladder tumors. RESULTS: The prevalence of S-p53Abs in patients with upper urinary tract tumors was higher than that in patients with bladder tumors (27.0% vs 17.5%). Especially, 34.8% of patients showed positive S-p53Abs in invasive upper urinary tract tumors (pT1 or more). In upper urinary tract tumors the prevalence of S-p53Abs significantly correlated with higher grade (p <0.01), higher stage (p = 0.02), positive lymph nodes (p = 0.03) and p53 nuclear accumulation (p <0.01). However, disease specific survival after nephroureterectomy did not differ between patients with negative and positive S-p53Abs. CONCLUSIONS: Our data suggest the possibility of the clinical application of S-p53Abs, especially for the detection of high grade or high stage tumors in the upper urinary tract. However, the usefulness of S-p53Abs as prognostic marker seems to be extremely limited in patients with urothelial tumors.     

Genetic detection of bladder cancer by microsatellite analysis of p16, RB1 and p53 tumor suppressor genes

PURPOSE: We investigated the incidence of genetic alterations in urine specimens from patients with bladder cancer. MATERIALS AND METHODS: A total of 28 cytological urine specimens were assessed for microsatellite alternations, and 15 microsatellite markers were located on p53, RB1 and p16 regions. In 15 patients DNA from tumor specimens was also available. RESULTS: Loss of heterozygosity was detected in 26 of 28 patients (93%) in at least 1 microsatellite marker. Allelic losses were found in 18 patients (64%) for the p16 locus, in 8 (29%) for the RB1 locus and in 17 (61%) for the p53 region. In contrast, no microsatellite alterations were found in the normal group without evidence of bladder cancer. In 11 cases genetic alterations in the cytological urine specimens were not detectable in the corresponding tumor specimen, suggesting heterogeneity of bladder cancer. CONCLUSIONS: The detection of loss of heterozygosity in cytological urine specimens may be a prognostic indicator of early detection of bladder cancer. Our results suggest that microsatellite analysis of urine specimens represents a novel, potentially useful, noninvasive clinical tool to detect bladder cancer.     

Breast cancer angiogenesis: A quantitative morphologic and doppler imaging study

Background: Tumor growth and metastases require the development of new vessels (angiogenesis). Angiogenesis, assessed by microvessel count using immunocytochemical stain of endothelial cells, has been shown to predict metastases and correlate with early death. Recently developed color Doppler mapping can detect the “tumor flow signals” in breast cancer and help to distinguish it from benign lesions. The question is, does this tumor vascularization assessed by color Doppler mapping correlate with the angiogenesis assessed by immunocytochemistry? Methods: Eighty-four patients admitted for breast surgery were studied. The final diagnosis was made by pathology for 52 malignancies and 32 benign lesions. The color Doppler mapping of the breast lesion was made preoperatively. The following parameters were assessed: (a) vessel location (peripheral or central); (b) density of color Doppler signals; and (c) maximum systolic velocity. Tumor angiogenesis was assessed by microvessel count under light microscopy using the platelet/endothelial cell adhesion molecule antibodies (CD31) method. The correlation between maximum velocity and microvessel count of breast cancer was examined. The clinical significance of maximum flow velocity of breast cancer with various clinicopathologic factors was assessed. Results: Color signals were detected in 48 cases of 52 malignancies (92%). All tumors demonstrated signals at the periphery of the lesion but in only 13 (27%) were the signals detected within the tumor. Color signals were scored as + + or + + + in 44 (92%) patients. Pulsed wave blood flow was shown in all these 48 tumors, with maximum velocities varying from 4 to 36 cm/s. Among the 32 benign lesions, color signals were detected in 10 (31%) and all were peripheral and scored subjectively as +. Evaluation of these color Doppler mapping parameters shows no significant correlation with microvessel counts using CD31 monoclonal antibodies. However, there was a positive association (p<0.05) between nodal metastases and higher tumor flow velocity in T1 (<2 cm) breast tumors but not in larger tumors. Conclusion: Although the color Doppler mapping has been shown to be useful in distinguishing benign from malignant breast lesions, the intensity of signal and velocity of flow had no correlation with the extent of angiogenesis of breast cancer. The presence of high-flow tumor signal in early breast carcinoma is significantly associated with the presence of axillary lymph node metastases.     

血清p53抗体异常高水平对消化道肿瘤的早期诊断价值分析

目的:探讨血清p53抗体异常高水平对消化道肿瘤的早期诊断的价值.方法:选取201 6年3月至201 9年3月来我院检查确诊为消化道肿瘤的患者80例为消化道肿瘤组,选取来我院健康体检的67例健康志愿者为健康对照组.通过酶联免疫吸附实验检测血清中人体抑癌基因p53及其抗体水平;通过RT-qPCR检测血清中细胞凋亡相关基因B...     

The prevalence and clinicopathologic correlate of p16INK4a, retinoblastoma and p53 immunoreactivity in locally advanced urinary bladder cancer

The purpose of the study was to investigate the prognostic value and clinicopathological correlate of tumor p53, p16 and Rb protein expression in patients with locally advanced urinary bladder cancer. Sixty-five patients (44 men and 21 women; 40 to 84 yrs old) with locally advanced urinary bladder cancer (21 pT2, 27pT3, 17pT4) undergoing radical cystectomy and bilateral pelvic lymph node dissection were followed up for 2 to 116 months (mean +/- SD: 30.02 +/- 6.46 months). Immunohistochemical staining for p53, Rb and p16 proteins were performed on surgically obtained, formalin fixed and paraffin embedded tissue sections. Thirty of the tumors (46.2%) were p53+, 52 of the tumors (80%) were p16- and 41 (63%) were Rb-. Only 5 of the tumors (7.7%) had normal expression of all three proteins. The tumor expression status of p53 could not be correlated with p16 (P = 1.000) or Rb (P = 1.000). Only a marginal inverse relationship was found between the expression of p16 and Rb (P = 0.056). Higher grade tumors had significantly lower percentage of p16 abnormality (P = 0.05), while higher grade (not higher stage) tumors had higher percentage of Rb abnormality (P = 0.0245). Univariate analysis showed that tumor expression of Rb or p16, alone or combined, had no predictive value on progression-free and disease-specific survival. It did, however, show a significant correlation between progression-free survival and tumor p53 and LN status (P = 0.032 and P = 0.0304) and a significant correlation between tumor stage disease-specific survival (P = 0.042). Multivariate analysis showed tumor stage and nodal status to be two significant independent indicators for progression-free survival (P = 0.0038 and P = 0.0049) and disease-specific survival (P = 0.0066 and P = 0.0484). It was also noteworthy that, after receiving postoperative adjuvant systemic M-VEC chemotherapy, patients with node-positive p53-normal tumors had significantly better progression-free and disease-specific survivals than those with node-positive p53-abnormal tumors (P = 0.036 and P = 0.0479, respectively). This study has found tumor expression of p53, p16 and Rb proteins in locally advanced bladder cancer to be frequently abnormal. Although multivariate analysis showed tumor stage and nodal status to be the only two statistically significant parameters, p53 may also serve as an additional prognostic predictor of the outcome of postoperative adjuvant systemic chemotherapy in patients with regional lymph node tumor involvement. Such patients with p53-normal tumors experienced significantly better progression-free and disease-specific survivals than those with p53-abnormal tumors.     

Metallothionein: early marker in the carcinogenesis of ulcerative colitis-associated colorectal carcinoma

Metallothioneins (MTs) are zinc-binding proteins whose overexpression may lead to sequestration of zinc ions and consequently to functional inactivation of the p53 tumor suppressor gene. The aim of the study was to investigate the potential role of MTs in the carcinogenesis of ulcerative colitis (UC) as well as possible effects on p53 function. The monoclonal antibodies E9 (anti-MT), DO-7, and 1801 (anti-p53) and the polyclonal antibody CM-1 (anti-p53) were used to stain formalin-fixed, paraffin-embedded colon specimens obtained from 14 patients with UC-associated colorectal carcinoma (CAC), 13 with high-grade dysplasia (HGD), 10 with low-grade dysplasia (LGD), and 30 with UC without dysplasia or carcinoma. Statistical significance (p <0.05) was assessed using Fisher's exact test. Positive MT staining (> 20% of tumor, dysplastic, or epithelial cells) was found in most UC and LGD but in only a small percentage of HGD and CAC (p <0.01 for CAC vs. UC and LGD vs. HGD). Positive p53 immunoreactivity was observed predominantly in HGD and CAC but not in LGD and UC (p <0.01 for CAC vs. UC and HGD vs. LGD). In histologically normal tissue neighboring CAC, significant MT expression was found in six of seven specimens with simultaneous lack of p53 expression. MT overexpression may represent an important early step in the development of CAC independent of p53 expression and should be investigated in the long term as an independent cancer risk factor in UC.