[China guideline for the screening and early detection of prostate cancer (2022, Beijing)].

Prostate cancer (PC) is one of the malignant tumors of the genitourinary system that occurs more often in elderly men. Screening, early diagnosis, and treatment of the PC high risk population are essential to improve the cure rate of PC. The development of the guideline for PC screening and early detection in line with epidemic characteristics of PC in China will greatly promote the homogeneity and quality of PC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. This guideline strictly followed the World Health Organization Handbook for Guideline Development and combined the most up-to-date evidence of PC screening, China's national conditions, and practical experience in cancer screening. A total of fifteen detailed evidence-based recommendations were provided with respect to the screening population, technology, procedure management, and quality control in the process of PC screening. This guideline aimed to standardize the practice of PC screening and improve the effectiveness and efficiency of PC prevention and control in China.

[Clinical features and prognostic value of TP53 mutation in Chinese prostate cancer patients].

Objective: To examine the clinical features and prognostic value of TP53 mutation in circulating tumor DNA(ctDNA) of Chinese prostate cancer patients. Methods: A prospective cohort of 239 prostate cancer patients diagnosed in the Department of Urology, Fudan University Shanghai Cancer Center from May 2018 to June 2019 was included. The age of diagnosis was(65.4±7.6) years(range: 45 to 85 years). Clinical data were collected from patient diagnosis and treatment records as well as follow-up surveys. TP53 mutations in plasma were detected by target sequence capture and second-generation sequencing. The relationship between TP53 mutation status and progression-free survival(PFS) was analyzed in patients who received any treatment lines. Kaplan-Meier analysis was performed in different subgroups, survival curves were drawn, and Log-rank test was used for comparison. Cox regression models were used to estimate multivariate adjusted HR and 95%CI associated with PFS. Results: In the cohort, 15.9%(38/239) patients had TP53 mutation. Patients with TP53 mutations had a higher rate of metastases initially diagnosed with prostate cancer (78.9% (30/38) vs. 60.2% (121/201), χ²=4.829, P=0.028), as well as a higher rate of castration resistance (68.4% (26/38) vs. 42.8% (86/201), χ²=8.434, P=0.004). Kaplan-Meier analysis revealed a median androgen-deprivation therapy-PFS of 13.0 months in patients with TP53 mutation and 17.0 months in patients with TP53 wild-type. The median abiraterone-PFS was 4.7 months for patients with TP53 mutation and 11.0 months for TP53 wild-type patients. The median docetaxel-PFS was 3.0 months in patients with TP53 mutation and 5.0 months in patients with TP53 wild-type. TP53 mutation was the undependent prognosis factor of PFS in patients treated with abiraterone(HR=2.23, 95%CI: 1.26 to 3.94, P=0.006) and docetaxel(HR=1.92, 95%CI: 1.01 to 3.66, P=0.047) had significant differences in PFS. Conclusions: TP53 mutations were associated with the presence of metastasis and castration resistance, and were also an independent prognostic factor for progression-free survival in patients treated with abiraterone and docetaxel.

[The prostate cancer precision screening program: a preliminary report after recruitment of 2 159 men].

Objective: The Chinese Anti-Cancer Association Genitourinary Cancer Committee Prostate Cancer Working Group released Consensus of prostate cancer (PCa) screening in 2017. This program aims to evaluate the methods and significance of prostate cancer precision screening in high risk population. Methods: A total of 2 159 eligible males enrolled from 13 community centers and 3 screening centers received PSA test from April 2017 to August 2018. Prostate-specific antigen (PSA) determination in serum with a cut-off of ≥4.0 ng/ml was the main screening test and indication for biopsy. The interviewer-administered questionnaire covered demographic characteristics and environmental exposure factors. The associations between these factors and prostate cancer risk were determined by multivariable unconditional logistic regression models. Results: Altogether, 271 cases (12.6%) had a confirmed PSA increase ≥ 4.0 µg/L (median 9.1, range 4.0-25.0). Subsequently, 57 subjects (21.0%) out of the 271 PSA-suspicious men underwent prostate biopsy, and 34 (59.6%) were confirmed as prostate cancer. Until now, the overall prostate cancer incidence in the first screening round was1.57%. There were no statistical differences in the distributions of PSA-suspicious and prostate cancer incidence between community centers and screening centers (P=0.578 and 0.735). Age (OR: 2.63; 95%CI: 1.84-3.75, P<0.001) and chronic prostatitis history (OR: 2.02; 95%CI: 1.55-2.63, P<0.001) were significantly associated with PSA level. After adjustment for these factors, older age (OR: 4.04; 95%CI: 1.71-9.59, P=0.002) and statins use (OR: 3.09; 95%CI: 1.25-7.69, P=0.015) were associated with an elevated risk of PCa. Conclusions: It is of substantial significance to screen prostate cancer in high risk population. Both community centers and screening centers methods are effective. Although largely underestimated, the incidence of PCa in the targeted Chinese population is higher than expected. Older men have a high risk of harboring PCa. Our study suggests a decreased risk of PCa in men with statins use. Prostate Cancer Precision Screening is promising to improve prostate cancer survival in China.

[Using the theory of precision medicine to optimize the multidisciplinary comprehensive treatment of prostate cancer].

In recent years, morbidity and mortality of prostate cancer in China have increased rapidly, and it has become a common malignant tumor among the top 5 male tumors in some areas. Multidisciplinary comprehensive treatment is the key to improve the survival rate and quality of life of prostate cancer. However, the drugs used to construct multidisciplinary comprehensive treatment were based on anatomy, treatment stage and clinical trials, which lacked individualized treatment for complex tumor scenarios. With the rapid development of precision medicine, molecular imaging, molecular typing and pharmacogenomics will be added to these three elements, which will help to improve the individualized level of multidisciplinary comprehensive treatment. This kind of precise multidisciplinary comprehensive treatment urgently needs the vigorous promotion of ideas, researchers and researches.

[Chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer: a short-term efficacy and safety analysis].

Objective: To investigate the short-term efficacy and adverse events of chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer. Methods: From March 2015 to August 2017, 55 patients with high-volume metastatic hormone sensitive prostate cancer were enrolled at Department of Urology, Fudan University Shanghai Cancer Center receiving chemotherapy combined with androgen-deprivation therapy. The age was 65(8) years (M(Q(R))) (range: 46 to 79 years). Patients were enrolled in the study for continuous androgen-deprivation therapy (medical or surgical castration), combined with docetaxel 75 mg/m(2) intravenous injection on the first day, repeated every 21 days (6 cycles). Endpoints included overall survival, progression-free survival of prostate cancer, prostate specific antigen (PSA) response rate, and adverse events. Results: The follow-up time was 21.2(11.7) months. The PSA value before chemotherapy was 144.9(415.3) µg/L. The days in patients undergoing androgen deprivation therapy before chemotherapy was 14(23) days. Four patients (7.3%) presented 0 in Eastern Cooperative Oncology Group scoring system and 51 patients(92.7%) presented 1. Thirty-nine patients (70.9%) completed more than 6 cycles of combined chemotherapy, 17 patients (30.9%) showed PSA<0.2 µg/L at 6 months after treatment, and 14 patients (25.5%) showed PSA<0.2 µg/L at 12 months after treatment. Twenty-eight patients (50.9%) had grade 3 to 4 neutropenia and 1 patient (1.8%) developed infectious neutropenia and died. Nausea and vomit occurred in 16 patients (29.1%). Twelve patients (21.8%) underwent dose adjustment due to adverse events in blood system. Conclusions: The short-term effect was confirmed in high-volume metastatic hormone sensitive prostate cancer using chemotherapy combined androgen-deprivation therapy, and the long-term effect remains to be seen. Myelosuppression during chemotherapy requires close attention, and taking timely examination is recommended.

[Use of prostate health index in diagnosing prostate cancer in Chinese men].

Objective: To investigate the value of prostate health index (PHI) in the diagnosis of prostate cancer in patients with total prostate specific antigen (tPSA) <20 µg/L. Methods: Totally 1 135 patients with tPSA<20 µg/L and prostate biopsy indications at Department of Urology, Fudan University Shanghai Cancer Center from March 2013 to April 2016 were enrolled in this study. They were tested for serum tPSA, free prostate specific antigen and prostate specific antigen isoform 2, from which PHI was calculated. Diagnostic efficacy of PHI and tPSA were evaluated using receiver operating characteristic (ROC) curve analysis. The detection rates of prostate cancer were calculated in different ranges of PHI. Subgroup analysis of 716 patients, who were aged 50 or above with tPSA in the range of 4 to 10 µg/L and digital rectal examination negative, was performed. Results: In the biopsied objects with tPSA<20 µg/L, PHI was significantly higher in prostate cancer patients than that in non-cancer patients (48.4(37.4) vs. 26.5(16.9), U=52 674.00, P=0.000), PHI was also significantly higher in high-grade prostate cancer patients than that of low-grade prostate cancer patients (44.5(30.8) vs. 56.4(42.5), U=23 314.00, P=0.000). The area under the curve (AUC) of PHI for diagnosing prostate cancer was significantly higher than that of tPSA (0.771 vs. 0.627, P=0.000). When PHI was in the range of <27, 27 to <36, 36 to <55 and ≥55, the probability of prostate cancer was 9.4% (95%CI: 7.0% to 12.2%), 16.3% (95%CI: 12.2% to 20.8%), 31.0% (95%CI: 25.9% to 37.3%) and 66.4% (95%CI: 58.9% to 74.2%), respectively. Subgroup analysis showed that the AUC of PHI in diagnosing prostate cancer was significantly higher than that of tPSA (0.764 vs. 0.569, P=0.000). When PHI was in the range of <27, 27 to <36, 36 to <55 and ≥55, the probability of prostate cancer was 8.1% (95%CI: 5.4% to 11.3%), 14.0% (95%CI: 9.1% to 19.9%), 30.8% (95%CI: 23.6% to 38.7%) and 78.8% (95%CI: 66.7% to 88.9%), respectively. Conclusion: PHI is superior to tPSA in the diagnosis of prostate cancer in Chinese men with tPSA<20 µg/L.

Effects of gum chewing on postoperative bowel motility after caesarean section: a meta-analysis of randomised controlled trials.

BACKGROUND: Gum chewing has been reported to enhance bowel motility and reduce postoperative ileus (POI). However, the efficacy remains imprecise for women following caesarean section. OBJECTIVES: To summarise and evaluate the current evidence for postoperative gum chewing on the recovery of bowel function following caesarean section. SEARCH STRATEGY: We searched studies from the following electronic databases: PubMed, EMBASE, SCOPUS and Cochrane Library from inception to 30 May 2013. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women after caesarean section; these RCTs should compared gum chewing with no gum chewing and reported on at least one of the outcomes: time to flatus, time to bowel sound, time to passing stool and length of hospital stay (LOS). DATA COLLECTION AND ANALYSIS: Study outcomes were presented as mean differences (for continuous data) with 95% confidence interval (95% CI). The risk of bias in the study results was assessed using the assessment tool from the Cochrane Handbook. MAIN RESULTS: Six RCTs including 939 women were included in our meta-analysis. The pooled results demonstrated that gum chewing is superior to no gum chewing with a reduction of 6.42 hours (95% CI -7.55 to -5.29) for time to first flatus, 3.62 hours (95% CI -6.41 to -0.83) for time to first bowel sound, 6.58 hours (95% CI -10.10 to -3.07) for time to first stool and 5.94 hours (95% CI -9.39 to -2.49) for LOS. In addition, no evidence emerged for any side effects caused by gum chewing. CONCLUSIONS: The current evidence suggests that gum chewing is associated with early recovery of bowel motility and shorter LOS for women after caesarean section. This safe and inexpensive intervention should be included in routine postoperative care following a caesarean section.

Secondary diabetes associated with 5-fluorouracil-based chemotherapy regimens in non-diabetic patients with colorectal cancer: results from a single-centre cohort study.

AIM: The aim of the study was to analyse the prevalence and characteristics of secondary diabetes induced by 5-fluorouracil (5-FU) based chemotherapy in non-diabetic patients with colorectal cancer (CRC). METHOD: A total of 422 consecutive CRC patients who received 5-FU-based chemotherapy were retrospectively analysed. Fasting plasma glucose (FPG) levels were determined before each cycle of chemotherapy during active treatment and regular follow-up. The prevalence and characteristics of secondary hyperglycaemia were investigated, with special focus on the clinical outcome. RESULTS: Among the 422 CRC patients, 60 had pre-existing hyperglycaemia. In the remaining 362 with normal FPG levels before chemotherapy, 42 (11.6%) and 41 (11.3%) patients developed diabetes and impaired fasting glucose during the study period. Among the 42 secondary diabetic patients, 22 (52.4%) received anti-diabetes drug therapy, in 7 (16.7%) cases the FPG level returned to normal without any active intervention, and 13 (30.9%) cases received diet control and physiotherapy. Thirty-one (8.6%) patients developed diabetes. Based on the Common Terminology Criteria for Adverse Events, an adverse event over Grade 3 occurred in seven cases during follow-up. Diabetes-related adverse events had a serious negative impact on chemotherapy in six cases. Diabetes-related death occurred in three patients. CONCLUSIONS: Secondary diabetes associated with 5-FU-based chemotherapy occurs in around 10% of CRC patients, with a significant negative impact on treatment and clinical outcome. 5-FU-related diabetes should be regarded as a common side effect of 5-FU treatment.

Clinicopathological characteristics, management and outcome of metastatic penoscrotal extramammary Paget's disease.

BACKGROUND: Metastatic penoscrotal extramammary Paget's disease (EMPD) has seldom been reported in the literature. OBJECTIVES: To improve the knowledge of the clinicopathological characteristics, management and outcome in patients with this disease. METHODS: The medical records and pathological slides of 10 patients with metastatic EMPD and 33 patients with nonmetastatic disease were reviewed. Immunohistochemical staining for epithelial cadherin (E-cadherin) was performed in the primary skin disease. All the 10 patients received 5-fluorouracil- or docetaxel-based chemotherapy. RESULTS: The most common sites of metastases were lymph nodes followed by bone. Patients with metastatic EMPD were more likely to be young and had elevated carcinoembryonic antigen (CEA) levels. Dermal or deeper invasion, lymphovascular embolization and negative expression of E-cadherin were important pathological predictors of metastatic potential. In invasive EMPD, lymphovascular embolization but not expression of E-cadherin was significantly associated with the risk of metastases. In three patients, (18)F-fluorodeoxyglucose positron emission tomography (PET)-computed tomography (CT) scans revealed occult lymph node metastases which were overlooked at conventional CT examinations. Two patients had complete response to the chemotherapy, three had partial response and five had progressive disease. The 2-year overall survival rate was 48% in patients with metastatic EMPD. In those patients with significantly elevated CEA level, the value of CEA paralleled the disease course. CONCLUSIONS: Metastatic EMPD tended to have dermal invasion and lymphovascular embolization. PET-CT scans were helpful in detecting distant metastases. 5-Fluorouracil- or docetaxel based-chemotherapy was effective in some patients. Serum CEA level can be a useful biomarker for monitoring disease course.

Sorafenib treatment of advanced renal cell carcinoma patients in daily practice: the large international PREDICT study.

BACKGROUND: Patients with advanced renal cell carcinoma in routine clinical practice can differ considerably from those in phase III studies. PATIENTS AND METHODS: PREDICT (Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with sorafenib) was a prospective, noninterventional study of open-label sorafenib for the treatment of advanced RCC conducted in 18 countries. Patient characteristics, therapy duration, tumor status, and tolerability were assessed at baseline and during routine follow-up. RESULTS: Overall, 2599 patients were evaluable for safety and 2311 for efficacy. The diverse population included patients with brain metastases (5%), non-clear-cell histologies (17%), high Memorial Sloan-Kettering Cancer Center risk score (11%), poor Eastern Cooperative Oncology Group performance status (PS ≥ 2, 29%), and patients with no previous nephrectomy (16%) or no previous systemic therapy (37%). The median duration of sorafenib therapy was 7.3 months and was similar in clinically relevant subgroups (eg, patients with PS 2, brain metastases, or concomitant hypertension or diabetes [range, 6.7-7.0 months]). The median duration of therapy was shorter for patients with PS 3 or non-clear-cell histologies (4.6 and 4.8 months, respectively). The most common drug-related adverse events were hand-foot skin reaction (20%), diarrhea (17%), and rash (8%). CONCLUSION: Sorafenib was generally well tolerated and provided clinical benefit in a large, diverse population of patients with advanced RCC treated in routine clinical practice.

[Mechanism of p53 gene mutation in the development of urologic cancer].

With DNA polymerase chain reaction-single strand conformation polymorphism assay followed by direct DNA sequencing, p53 gene mutation was examined in bladder transitional epithelial cell carcinoma, renal cell carcinoma and testicular seminoma. p53 gene mutation was found in 7 cases (35%) of bladder carcinoma and 4 cases (23.5%) of testicular seminoma. Inactivation of Rb gene and activation of ras and c-erbB-2 were also studied. The results suggest that development of urologic neoplasms is closely associated with p53 gene mutation and involves loss of expression of Rb and aberrant expression of ras and c-erbB-2.

[Expression of mutant P53 gene protein product in human bladder carcinoma].

Expression of P53 protein was detected immunohistochemically in formalin-fixed, paraffin-embedded tissues from 67 patients with bladder carcinoma and 6 normal bladder controls. P53 protein was found positively in 34 of the 67 tumors, whereas no normal bladder controls and no non-cancer tissue cells on tumor sections was stained positively for P53 protein. The percentage of staining for P53 was higher in poorly-differentiated and in invasive tumors than in well and moderately differentiated and in superficial tumors. We also found that P53 positive staining was closely related to tumors recurrence. Hence, the expression of P53 may be used as a tumor marker predicting the histograde, clinical stage and recurrence.

Polymorphisms at long non-coding RNAs and prostate cancer risk in an eastern Chinese population.

BACKGROUND: Controversial data on the association of single-nucleotide polymorphisms (SNPs, rs3787016G>A and rs10773338G>A) in long non-coding RNA (lncRNA) with prostate cancer risk were emerged. Considering possible genetic differences among populations, we conducted the present study to clarify these discrepancies and re-validate these results in an eastern Chinese population and thus provide clues for new therapeutic targets of prostate cancer. METHODS: Genotypes of these two SNPs from 1015 ethnic Han Chinese patients with prostate cancer and 1032 cancer-free controls were determined by Taqman assays. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations. RESULTS: The association of rs3787016 A variant genotypes with a significantly higher prostate cancer risk were found (adjusted OR = 1.418, 95% CI = 1.090-1.844 for AA vs GG). Stratification analysis indicated that the risk of rs3787016 variant AG/AA genotypes was more evident in younger subjects, ever smoking, patients with Gleason score ⩾ 7(4+3) and highly aggressive status. All these risks were not present for rs10773338G>A. CONCLUSIONS: These findings suggested that lncRNA SNPs may contribute to prostate cancer risk in an eastern Chinese population. Larger and well-designed studies with different ethnic populations are warranted to validate our findings.

Conditional survival in patients treated with vascular endothelial growth factor-targeted therapy for advanced renal cell carcinoma.

PURPOSE: Conditional survival (CS) offers more relevant prognostic information for patients once they have survived for some time. The objective of this study was to determine the CS for advanced renal cell carcinoma (RCC) patients treated with vascular endothelial growth factor-targeted therapy. METHODS: A total of 345 patients treated between 2006 and 2011 fulfilled the inclusion criteria and were reviewed for analyses. The 1-year conditional and actual survival rates were calculated for survivors from treatment to month 24. Subgroup-specific CS rates were generated after adjustment of the covariate influence. The Cox proportional hazard models were used to assess the prognostic factors at baseline and 1-year landmark. RESULTS: The probabilities of surviving an additional year given survival to 6, 12, 18, and 24 months were 72.2, 76.3, 78.2, and 78.6 %, respectively. Remarkable increase in CS was observed in patients initially classified as intermediate or poor risk according to Heng risk groups. For patients survived 24 months after treatment, the adjusted CS for the following year was over 80 % regardless of initial risk attribution. Compared to baseline analysis, Heng risk groups were less predictive of survivorship after surviving 1 year. The addition of disease control status to multifactorial model significantly improved survival estimation for 1-year survivors (p < 0.01). CONCLUSIONS: CS provides useful information regarding life expectancy for survivors of advanced RCC treated with targeted therapy. Furthermore, disease control status within a specific period of time is critical to the prediction of subsequent survival.

Efforts to resolve the contradictions in early diagnosis of prostate cancer: a comparison of different algorithms of sarcosine in urine.

Controversial data on sarcosine as a promising biomarker for prostate cancer (PCa) detection are present. The objective was to clarify these discrepancies and reevaluate the potential value of sarcosine in PCa. Sarcosine algorithms (supernatant and sediment sarcosine/creatinine, supernatant and sediment log2 (sarcosine/alanine)) in urine samples from 71 untreated patients with PCa, 39 patients with no evidence of malignancy (NEM) and 20 healthy women and men were quantified by liquid chromatography/tandem mass spectrometry. Although any sarcosine algorithms were significantly higher in PCa patients than in NEM patients (all P<0.05), comparable sarcosine values were measured in healthy women and men. Additionally, neither biopsy Gleason score nor clinical T-stage were correlated with sarcosine algorithms (all P>0.05), and receiver operating characteristic curve analysis indicated that the diagnostic power of any of sarcosine algorithms was nonsignificantly higher than that of serum and urine PSA, but nonsignificantly lower than prostate cancer antigen 3 (PCA3) and the percent-free PSA (%fPSA). Improved diagnostic performances were observed when any of sarcosine algorithms was combined with PCA3 or %fPSA. In conclusion, the predictive power of sarcosine in PCa is modest compared with PCA3 and %fPSA. Sarcosine, which awaits more validation before it reaches the clinic, could be included into the list of candidate PCa biomarkers.

Therapeutic efficacy of Traditional Chinese Medicine 319 recipe on hepatic fibrosis induced by carbon tetrachloride in rats.

BACKGROUND/AIMS: Hepatic fibrosis is a consequence of severe liver damage that occurs in many patients with chronic liver diseases. TCM 319 recipe is a Chinese Medicine formula which consists of six Chinese herbs. In this study, we investigated the anti-fibrotic efficacy and mechanisms of TCM 319 recipe. METHODS: Hepatic fibrosis in rats was induced by carbon tetrachloride (CCl4). 34 male adult SD rats were allocated into five groups (group 1-concomitant CCl4 and TCM 319 recipe for 8 weeks; group 2-CCl4 for 4 weeks and then CCl4 and TCM 319 recipe for 4 weeks; group 3-CCl4 alone for 8 weeks; group 4-TCM 319 recipe only for 8 weeks; group 5-untreated controls). After 8 weeks of treatment, serum ALT assay, liver tissue histological examination and immunostaining were carried out to examine the liver function and fibrosis degree. The expression levels of platelet derived growth factor (PDGF-B), PDGF-Rbeta, and transforming growth factor-beta 1 (TGF-beta1) were measured by quantitative RT-PCR and western blot. RESULTS: TCM 319 recipe reduced liver injury and attenuated hepatic fibrosis in group 1 compared with that in group 3. TCM 319 recipe suppressed the mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1). In addition, treatment with TCM 319 recipe significantly down-regulated mRNA expression of PDGF-B and PDGF-Rbeta, and it also suppressed protein expression of PDGF-Rbeta and TGF-beta1. CONCLUSIONS: TCM 319 recipe extracts could attenuate hepatic fibrosis induced by CCl4 in rats. The anti-fibrotic effect of TCM 319 recipe is associated with the down-regulation of mRNA expression of TIMP-1, PDGF-B and PDGF-Rbeta, and with the suppression of protein expression of PDGF-Rbeta and TGF-beta1.

Expression of p53 product in Chinese human bladder carcinoma.

Expression of p53 protein was examined in 67 cases of primary transitional cell carcinoma of the bladder and 6 normal controls using an immunohistochemical method on paraffin sections. Positive nuclear staining for p53 in malignant cells was found in 34 (51%) of the 67 cancer patients; no positive staining for p53 was detected in any of the normal controls or in the benign cells, including stromal and inflammatory cells, within the tumor tissue. There were 8 positive cases (33%) in 24 grade G1 tumors, 12 (48%) in 25 G2 tumors and 14 (78%) in 18 G3 tumors. p53 protein was detected positively in 14 (36%) of 39 superficial tumors (Tis-T1) and in 20 (71%) of 28 invasive tumors (T2-T4). Thus, positive staining for p53 was found more frequently in poorly differentiated tumors (chi-squared test: G3/G1 + G2 P < 0.01) and in invasive tumors (chi-squared test: T2-T4/Tis-T1 P < 0.01). Expression of p53 was also closely associated with recurrence of tumors. Alterations in p53 expression may be of prognostic value in cases of bladder transitional cell carcinoma.

Correlation between the expression of oncogenes ras and c-erbB-2 and the biological behavior of bladder tumors.

Expression of the ras and the c-erbB-2 oncogene products was investigated in 56 cases of human bladder transitional cell carcinoma and 6 samples of human normal bladder tissue using an immunohistochemical method. Thirty of the 56 cases of bladder tumor were found to be immunohistologically positive with the monoclonal anti-ras p21 antibody, while 19 of 56 cases were positive with the polyclonal anti-c-erbB-2 oncoprotein antibody. All 6 controls were negative with both antibodies. The ras p21 positive staining was found more frequently in the well or moderately differentiated, superficial and non-recurrent tumors than in the poorly differentiated (p < 0.01), muscle invasive (p < 0.05) and recurrent tumors (p < 0.01), while the c-erbB-2 gene product was more commonly detected in high-grade (p < 0.01), invasive (p < 0.01) and recurrent tumors (p < 0.05). Thus, the expression of either ras or c-erbB-2 was closely associated with the histological grade, clinical stage and recurrence of bladder transitional cell carcinomas.

p53 gene mutations in Chinese human testicular seminoma.

Genomic deoxyribonucleic acid from 17 primary human testicular seminomas was screened for the presence of mutations in exons 5 to 8 of gene p53, using the single strand conformation polymorphism assay, followed by direct deoxyribonucleic acid sequencing. The p53 mutations in 1 allele leading to an amino acid change but a normal (wild-type) sequence in the remaining allele were identified in 4 of 17 seminomas (23.5%). Sites of mutations were in exon 5 (codon 141), exon 7 (codon 238, codon 258) and exon 8 (codon 270). The present study suggested that mutation of the p53 gene is involved in the development of human testicular seminoma as in the case of several other types of human cancers.