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Biomedical subjects

L Cheng

Publications and source records attributed to L Cheng.

At least 127 records · Page 7Linked to original sources
PubMed2000

Prevalence, correlates, and natural history of epiretinal membranes surrounding idiopathic macular holes. Virectomy for Macular Hole Study Group.

OBJECTIVE: To report on the prevalence, correlates, and natural history of epiretinal membranes (ERM) in eyes with stage II or III/IV macular holes. DESIGN: A subgroup analysis arising from a multicentered, controlled, randomized clinical trial. SETTING: Community and university-based ophthalmology clinics. PATIENTS: Two hundred twenty four eyes with stage II or III/IV macular holes. INTERVENTIONS: No intervention for 100 eyes randomly assigned to observation. OUTCOME MEASURES: Grade of ERM determined by stereoscopic examination of fundus photographs at baseline and at 3, 6, 12, and 24 months of follow-up. RESULTS: The prevalence of ERM was 65% (145 of 224 eyes), was greater in pseudophakic than in phakic eyes (80% vs. 63%, P = 0.10), and increased with increasing severity of the hole (P < 0.0001). Stage III/IV eyes with ERM had a significantly larger hole size than did eyes without ERM (P < 0.01); however, no association between presence of ERM and visual acuity was found (P > 0.5). In the 100 phakic eyes that were randomly assigned to observation, there was a significant increase in the severity of ERM over follow-up (P < 0.0001). CONCLUSIONS: ERM are common in eyes with full-thickness idiopathic macular holes. Although ERM prevalence increases with severity and size of the macular hole, the presence of ERM are not closely correlated with visual acuity. These factors may be important in considering the removal of ERM during vitrectomy for macular hole.

California↗
PubMed2000

Evidence that axon-derived neuregulin promotes oligodendrocyte survival in the developing rat optic nerve.

It was previously shown that newly formed oligodendrocytes depend on axons for their survival, but the nature of the axon-derived survival signal(s) remained unknown. We show here that neuregulin (NRG) supports the survival of purified oligodendrocytes and aged oligodendrocyte precursor cells (OPCs) but not of young OPCs. We demonstrate that axons promote the survival of purified oligodendrocytes and that this effect is inhibited if NRG is neutralized. In the developing rat optic nerve, we provide evidence that delivery of NRG decreases both normal oligodendrocyte death and the extra oligodendrocyte death induced by nerve transection, whereas neutralization of endogenous NRG increases the normal death. These results suggest that NRG is an axon-associated survival signal for developing oligodendrocytes.

Animals↗
PubMed2000

DNA repair capacity in healthy medical students during and after exam stress.

There has been extensive research into the effects of stress on immune function but little on the effects of stress on DNA repair capacity (DRC), a process central to maintaining a normal cell cycle. Defective DRC is one of the factors responsible for carcinogenesis. In the present study we assessed DRC in healthy medical students during times of high and low stress. Sixteen medical students were evaluated during the third day of a 5-day exam period and then again 3 weeks later, after vacation. At both time points, participants underwent a brief physical examination, had venous blood drawn, and completed questionnaires to identify subjective stress levels. The DRC was assessed by the host-cell reaction assay, which measures nucleotide excision repair capacity. Participants reported significantly higher levels of subjective stress during the exam period than after vacation. DRC was also significantly higher during the exam period than after vacation, suggesting a positive association between subject stress levels and DRC. The results are discussed in relation to previous findings and implications for cancer research.

Adult↗
PubMed2000

Extranodal extension in lymph node-positive prostate cancer.

Evaluation of extranodal tumor extension may provide prognostic information for patients with epithelial malignancies. However, its importance for the patient who has prostate cancer with regional lymph node metastasis requires further investigation and clarification. This study was performed to evaluate the prognostic significance of extranodal extension (ENE) in a large series of node-positive patients. The study group included 212 node-positive patients who were treated by bilateral pelvic lymphadenectomy, radical retropubic prostatectomy, and androgen deprivation between 1987 and 1992 at the Mayo Clinic. ENE was defined as cancer perforating through the lymph node capsule into perinodal tissue. Nodal cancer volume was measured by the grid method. Univariate and multivariate risk ratios (RR) for distant metastasis-free and cancer-specific survival were estimated using the Cox proportional model. The mean follow-up was 6.3 years (median, 6.1 years). Distant metastasis-free and cancer-specific survival at 5 years for all patients was 91% and 95%, respectively. ENE was found in 126 of 212 patients (59%). The presence of ENE was not significantly associated with distant metastasis-free (RR = 1.6; 95% confidence interval [CI], 0.7 to 3.9) or cancer-specific survival (RR = 2.2; 95% CI, 0.7 to 6.8). Among 98 patients with a single positive node, there was no significant difference in distant metastasis or cancer-specific survival according to the presence of ENE (P = .88 and P = .36, respectively). After adjusting for Gleason score, DNA ploidy, and ENE, only nodal cancer volume was significantly associated with adverse distant metastasis-free (RR = 1.9; 95% CI, 1.5 to 2.8) and cancer-specific survival (RR = 1.4; 95% CI, 1.1 to 1.9). Our data indicate that the presence of ENE is not associated with unfavorable survival in patients with node-positive prostate cancer treated by radical retropubic prostatectomy, bilateral pelvic lymphadenectomy, and androgen deprivation therapy. In contrast, nodal cancer volume was predictive of distant metastasis-free survival and cancer-specific survival.

Adenocarcinoma↗
PubMed2000

The A5.1 allele of the major histocompatibility complex class I chain-related gene A is associated with psoriasis vulgaris in Chinese.

BACKGROUND: Recent studies have demonstrated an association of a polymorphic (GCT)n triplet repeat in the transmembrane (TM) region of the major histocompatibility complex (MHC) class I chain-related gene A (MICA), one of the MHC class I chain-related (MIC) family members, with some autoimmune diseases, including Behçet's disease, acute anterior uveitis, Takayasu's arteritis and others. OBJECTIVES: The aim of this study was to examine whether the MICA gene is associated with psoriasis vulgaris (PS) in Chinese. PATIENTS AND METHODS: The (GCT)n polymorphism of the MICA gene was investigated in 200 healthy Chinese of Han origin and 300 patients with PS by polymerase chain reaction amplification and denaturing polyacrylamide gel electrophoresis. RESULTS: Five alleles, namely A4, A5, A6, A9 and A5.1 were found in both groups. Comparison of the data from both groups revealed that the A5.1 allele was present at a significantly higher frequency in the patient group (41.5%) than in the control group (23.0%) (Pc < 0.0001, Pc means the probability of a comparison with the control group). The frequency of A5.1-positive cases was also significantly increased in the patient group (68.0%) as compared with the controls (38.0%) (Pc < 0.0001). Furthermore, the carrier frequency of A5.1-positive was significantly increased in psoriatic patients with a positive family history and with early onset as compared with sporadic cases (Pc = 0.0005) and with late onset PS (Pc = 0.002). CONCLUSIONS: These results suggest that the MICA gene may be associated with the development of PS in Chinese.

Adolescent↗
PubMed2000

10q23.3 loss of heterozygosity is higher in lymph node-positive (pT2-3,N+) versus lymph node-negative (pT2-3,N0) prostate cancer.

Loss of heterozygosity (LOH) in the region of 10q23.3 has been associated with multiple tumors, including glioblastoma multiforme, melanoma, endometrial carcinoma, and prostate carcinoma. The tumor suppressor gene, PTEN/MMAC1, is also located in this region, and, in addition to other tumor types (eg, glioblastoma multiforme, endometrial, and melanoma), PTEN/MMAC1 mutations have been found in prostate cancer cell lines, xenografts, and hormone refractory prostate cancer tissue specimens. The aim of this study was to evaluate LOH at 10q23.3 as a marker of cancer progression in node-positive prostate cancer. Genetic alterations in the region of 10q23.3 were assessed in 23 node-positive (pT2-3, N+) and 44 node-negative prostate (pT2-3, N0) cancers with D10S532, D10S1687, D10S541, and D10S583 flanking polymorphic genetic markers; PTENCA, a genetic marker within PTEN/MMAC1, was also tested. Using DNA from paired normal and microdissected tumor samples, LOH at microsatellite loci was determined after polymerase chain reaction amplification. LOH in at least 1 marker was identified in 14% (6 of 44) of lymph node-negative and 43% (10 of 23) of lymph node-positive prostate cancers (chi-square test, P = .007). This increase in genetic alterations in node-positive prostate cancer suggests that 10q23.3 is a marker for metastatic progression.

Adenocarcinoma↗
PubMed2000

Cyclooxygenase-2 expression in human pancreatic adenocarcinomas.

Cyclooxygenase-2 (COX-2) expression is up-regulated in several types of human cancers and has also been directly linked to carcinogenesis. To investigate the role of COX-2 in pancreatic cancer, we evaluated COX-2 protein expression in primary human pancreatic adenocarcinomas (n = 23) and matched normal adjacent tissue (n = 11) by immunoblot analysis. COX-2 expression was found to be significantly elevated in the pancreatic tumor specimens compared with normal pancreatic tissue. To examine whether the elevated levels of COX-2 protein observed in pancreatic tumors correlated with the presence of oncogenic K-ras, we determined the K-ras mutation status in a subset of the tumors and corresponding normal tissues. The presence of oncogenic K-ras did not correlate with the level of COX-2 protein expressed in the pancreatic adenocarcinomas analyzed. These observations were also confirmed in a panel of human pancreatic tumor cell lines. Furthermore, in the pancreatic tumor cell line expressing the highest level of COX-2 (BxPC-3), COX-2 expression was demonstrated to be independent of Erk1/2 activation. The lack of correlation between COX-2 and oncogenic K-ras expression suggests that Ras activation may not be sufficient to induce COX-2 expression in pancreatic tumor cells and that the aberrant activation of signaling pathways other than Ras may be required for up-regulating COX-2 expression. We also report that the COX inhibitors sulindac, indomethacin and NS-398 inhibit cell growth in both COX-2-positive (BxPC-3) and COX-2-negative (PaCa-2) pancreatic tumor cell lines. However, suppression of cell growth by indomethacin and NS-398 was significantly greater in the BxPC-3 cell line compared with the PaCa-2 cell line (P = 0.004 and P < 0.001, respectively). In addition, the three COX inhibitors reduce prostaglandin E(2) levels in the BxPC-3 cell line. Taken together, our data suggest that COX-2 may play an important role in pancreatic tumorigenesis and therefore be a promising chemotherapeutic target for the treatment of pancreatic cancer.

Adenocarcinoma↗
PubMed2000

Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations.

The prospect of a hormonal male contraceptive is no longer distant. Data on the potential impact of this improvement in contraceptive provision, however, is limited, particularly between different cultures. We have therefore carried out a multi-centre study to assess men's attitudes to proposed novel hormonal methods. Questionnaire-based structured interviews were administered to men in Edinburgh, Cape Town, Shanghai and Hong Kong. Approximately 450 men were interviewed in Edinburgh, Shanghai and Hong Kong, and a slightly larger group (n = 493) in Cape Town to give samples (n > 150) of black, coloured and white men. Knowledge of existing male and female methods of contraception was high in all centres and groups. The majority of men welcomed a new hormonal method of contraception, 44-83% stating that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injectable form (most popularly given at 3-6 month intervals); long-acting implants were least so except in Shanghai. Familiarity with comparable female methods appeared to influence acceptability, for both oral and injectable methods. Hong Kong was the only centre where a male method (condom) was currently the most commonly used; men there appeared to rate the convenience of condoms highly while being least likely to think that they provided effective protection against pregnancy compared to other centres, and were least enthusiastic about novel male methods. The acceptability of potential male hormonal methods of contraception was high in some groups but showed wide variability, determining factors including cultural background and current contraceptive usage. These results suggest that the emerging emphasis that men should have greater involvement in family planning will be substantiated when appropriate contraceptive methods become available.

Adolescent↗
PubMed2000

Would women trust their partners to use a male pill?

Despite a renewed interest in the development of hormonal contraceptives for men, many discussions about the potential acceptability of a 'male pill' end by speculating whether women would trust their partners to use the method reliably. To determine the views of women, we undertook a survey of 1894 women attending family planning clinics in Scotland (450), China (900) and South Africa (544). In all centres over 65% of women thought that the responsibility for contraception falls too much on women. More than 90% in South Africa and Scotland thought that a 'male pill' was a good idea, with Chinese women (71% in Hong Kong and 87% in Shanghai) only slightly less positive. Only 13% of the total sample did not think that hormonal male contraception was a good idea and only 36 women (2% of the total) said that they would not trust their partner to use it. 78% of Scottish women, 71% of Shanghai women, and 78% of white women and 40% of black and coloured women in Cape Town thought that they would use the method. This survey should dispel the myth that women would not trust their partners to use a 'male pill' reliably and illustrates the potential market for the method.

Adolescent↗
PubMed2000

Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel.

It has been suggested that the administration of an anti-progesterone might improve bleeding patterns in women with irregular bleeding while using low-dose progestin-only contraception. We report the findings of a double-blind, randomized, placebo-controlled trial of mifepristone 50 mg taken once every 4 weeks in 100 Chinese women (50 subjects and 50 controls) complaining of frequent and irregular bleeding while using a levonorgestrel-releasing subdermal contraceptive implant. In all women, regardless of treatment, the frequency of bleeding decreased significantly over 360 days of observation. Women recorded significantly shorter episodes of bleeding (P: < 0.0002) during mifepristone treatment than during the 90 days before treatment started. In contrast, the duration of bleeding episodes fell more gradually in placebo-treated controls. Women using mifepristone were more likely to find treatment acceptable than women receiving a placebo tablet (P: < 0.01). Despite concern that anti-progestogenic effects may jeopardize contraception, there were no pregnancies. This approach may offer a useful strategy to improve continuation rates by alleviating unwanted side-effects until bleeding patterns improve spontaneously with time.

Adolescent↗
PubMed2000

Rubisco activation state decreases with increasing nitrogen content in apple leaves.

Based on the curvilinear relationship between leaf nitrogen content and the initial slope of the response of CO(2) assimilation (A:) to intercellular CO(2) concentrations (C:(i)) in apple, it is hypothesized that Rubisco activation state decreases with increasing leaf N content and this decreased activation state accounts for the curvilinear relationship between leaf N and CO(2) assimilation. A range of leaf N content (1.0-5.0 g m(-2)) was achieved by fertilizing bench-grafted Fuji/M.26 apple (Malus domestica Borkh.) trees for 45 d with different N concentrations, using a modified Hoagland's solution. Analysis of A:/C:(i) curves under saturating light indicated that CO(2) assimilation at ambient CO(2) fell within the Rubisco limitation region of the A:/C:(i) curves, regardless of leaf N status. Initial Rubisco activity showed a curvilinear response to leaf N. In contrast, total Rubisco activity increased linearly with increasing leaf N throughout the leaf N range. As a result, Rubisco activation state decreased with increasing leaf N. Both light-saturated CO(2) assimilation at ambient CO(2) and the initial slope of the A:/C:(i) curves were linearly related to initial Rubisco activity, but curvilinearly related to total Rubisco activity. The curvatures in the relationships of both light-saturated CO(2) assimilation at ambient CO(2) and the initial slope of the A:/C:(i) curves with total Rubisco activity were more pronounced than in their relationships with leaf N. This was because the ratio of total Rubisco activity to leaf N increased with increasing leaf N. As leaf N increased, photosynthetic N use efficiency declined with decreasing Rubisco activation state.

Carbon Dioxide↗
PubMed2000

Characterization and predictors of prostate specific antigen progression rates after radical retropubic prostatectomy.

PURPOSE: Detectable serum prostate specific antigen (PSA) after radical prostatectomy indicates recurrent disease and treatment failure. We characterized PSA recurrence after prostatectomy and identified predictors of rapid PSA progression. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 165 patients with detectable PSA after radical prostatectomy to characterize the rate of PSA increase and correlate this rate with the possible predictors of rapid PSA progression known at prostatectomy. RESULTS: For a median of 48 months postoperatively we followed 142 patients with PSA recurrence after radical prostatectomy who received no immediate adjuvant therapy. PSA doubling time was less than 6, greater than 6, 12, 18 and 24 months in 46%, 54%, 18%, 11% and 9% of cases, while time to PSA 50 ng./ml. was greater than 5, 10, 15 and 20 years in 69%, 34%, 22% and 9%, respectively. Univariate and multivariate analyses revealed that rapid PSA doubling time was associated with Gleason secondary grade, Gleason score and time to initial detectable PSA (p = 0.019, 0.031 and 0.0001, and p = 0.043, 0.045 and 0.0001, respectively). CONCLUSIONS: PSA recurrence progresses at a greatly variable rate and many recurrences progress slowly with a long doubling time. Gleason secondary grade and score appear to be predictive of rapid PSA progression. No other pathological features were predictive of rapid PSA progression.

Analysis of Variance↗
PubMed2000

Preoperative prediction of surgical margin status in patients with prostate cancer treated by radical prostatectomy.

PURPOSE: We sought to determine the preoperative factors associated with surgical margin status in patients who underwent radical prostatectomy for prostate cancer. PATIENTS AND METHODS: The study group consisted of 339 patients who were treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy at the Mayo Clinic. None received preoperative adjuvant therapy. The mean age at the time of surgery was 66 years (range, 45 to 79 years). All specimens were totally embedded and whole-mounted. Positive surgical margin was defined as the presence of cancer cells at the inked margins. Numerous pathologic characteristics in needle biopsies and preoperative clinical findings were analyzed. RESULTS: The overall margin positivity rate was 24%. In univariate analysis, preoperative serum prostate-specific antigen (PSA) level, Gleason score, perineural invasion, percentage of cancer in the biopsy specimens, and number and percentage of biopsy cores involved by cancer were all associated with positive surgical margins. In multivariate analysis, preoperative serum PSA level (odds ratio for a doubling of PSA levels, 1.9; 95% confidence interval, 1.5 to 2.4; P <.001) and percentage of cancer in the biopsy specimens (odds ratio for a 10% increase, 1.3; 95% confidence interval, 1.2 to 1.4; P <.001) were predictive of margin status in radical prostatectomy. With use of preoperative serum PSA level and percentage of cancer in the biopsy as predictors of surgical margins, the overall accuracy as measured by the area under the receiver operating characteristic curve was 0.74. CONCLUSION: Preoperative serum PSA level and percentage of cancer in the biopsy specimens were independently associated with surgical margin status in patients who underwent radical prostatectomy for prostate cancer. The combination of these two factors provides a high level of predictive accuracy for margin status.

Aged↗
PubMed2000

Grading and staging of bladder carcinoma in transurethral resection specimens. Correlation with 105 matched cystectomy specimens.

We compared the grading and staging of transurethral resection of the bladder (TURB) and cystectomy specimens for 105 patients who underwent radical cystectomy for urothelial carcinoma between 1980 and 1984. Of 105 patients, 96% underwent cystectomy within 100 days of TURB (median interval, 10 days). Grading was performed according to the 1998 World Health Organization/International Society of Urologic Pathology grading system and staging according to the 1997 TNM classification. Histologic grade was low-grade, 13; high-grade, 92 in TURB specimens; low-grade, 17; high-grade, 88 in cystectomy specimens. Pathologic stage was Ta, 15; T1, 55; and T2, 35 in TURB specimens; Ta, 5; T1, 19; T2, 19; T3, 46; and T4, 16 in cystectomy specimens. Histologic grade at TURB was associated with pathologic stage at cystectomy (P < .001). When all advanced-stage (muscle-invasive) carcinomas (pT2 or more) were considered together, 55 patients were understaged by TURB, 4 had higher stage in TURB than in cystectomy, and 46 were the same stage as by cystectomy. Forty-three of 55 patients with stage T1 carcinoma at TURB had advanced-stage carcinoma at cystectomy, including 34 who had extravesicular extension (pT3 or more). We found pathologic understanding by TURB occurs in a significant number of patients with bladder cancer; the newly proposed grading system predicted final pathologic stage.

Adult↗
PubMed2000

Expression of FGFR3 with the G380R achondroplasia mutation inhibits proliferation and maturation of CFK2 chondrocytic cells.

A G380R substitution in the transmembrane-spanning region of FGFR3 (FGFR3Ach) results in constitutive receptor kinase activity and is the most common cause of achondroplastic dwarfism in humans. The epiphyseal growth plates of affected individuals are disorganized and hypocellular and show aberrant chondrocyte maturation. To examine the molecular basis of these abnormalities, we used a chondrocytic cell line, CFK2, to stably express the b variant of wild-type FGFR3 or the the constitutively active FGFR3Ach. Overexpression of FGFR3 had minimal effects on CFK2 proliferation and maturation compared with the severe growth retardation found in cells expressing FGFR3Ach. Cells expressing the mutant receptor also showed an abnormal apoptotic response to serum deprivation and failed to undergo differentiation under appropriate culture conditions. These changes were associated with altered expression of integrin subunits, which effectively led to a switch in substrate preference of the immature cell from fibronectin to type II collagen. These in vitro observations support those from in vivo studies indicating that FGFR3 mediates an inhibitory influence on chondrocyte proliferation. We now suggest that the mechanism is related to altered integrin expression.

Achondroplasia↗
PubMed2000

Intravitreal toxicology and duration of efficacy of a novel antiviral lipid prodrug of ganciclovir in liposome formulation.

PURPOSE: To evaluate the intraocular safety and antiviral treatment efficacy of the sustained lipid prodrug of ganciclovir, 1-O-hexadecylpropanediol-3-phospho-ganciclovir (HDP-P-GCV), as an intravitreal injectable drug system for viral retinitis. METHODS: HDP-P-GCV was synthesized by coupling 1-O-hexadecyl-propanediol-3-phosphate to either free hydroxyl of ganciclovir in pyridine with dicyclohexylcarbodiimide as catalyst. The compound was formulated into liposomes. The antiviral activity was assessed by DNA reduction in vitro, and intraocular safety was assessed by ophthalmoscopy, electrophysiology, and histology after intravitreal injections, with resultant intravitreal concentrations of 0.2, 0.632, 1.12, and 2 mM. The treatment efficacy was evaluated by simultaneous intravitreal injection of HDP-P-GCV and herpes simplex virus type 1 (HSV-1) or by intravitreal injection of HDP-P-GCV at various times before HSV-1 intravitreal inoculation. Retinitis was scored with ophthalmoscopy and compared with controls. RESULTS: In vitro, the IC50 of HDP-P-GCV against HSV-1 and human cytomegalovirus (HCMV) infected cells was 0.02 and 0.6 microM, respectively. In rabbits in vivo, HDP-P-GCV dispersed evenly and maintained a good vitreous clarity at all doses except 2 mM final intravitreal concentration. Although cataracts were observed in some eyes at the higher doses, they were not observed in eyes with 0.2 mM final intravitreal concentration. No other indications of ocular toxicity were observed. Intravitreal injection of HDP-P-GCV with resultant 0.2 mM intravitreal concentration in the HSV-1 retinitis rabbit model demonstrated a complete protection of the retina with the simultaneous treatment strategy and a 4 (P = 0.03) to 6-(P = 0.058) week significant protection of retina with the pretreatment strategies when compared with ganciclovir or blank liposome controls. CONCLUSIONS: In the rabbit model of HSV-1 retinitis HDP-P-GCV acts as a long-lasting intravitreal injectable anti-CMV or anti-HSV compound. This self-assembling liposome system could be applicable for many compounds available for intraocular diseases.

Animals↗
PubMed2000

Outcome prediction with p53 immunostaining after radical prostatectomy in patients with locally advanced prostate cancer.

PURPOSE: Conventional pathological variables in prostate cancer may not provide optimal prediction of patient outcome. Pathological findings and p53 immunostaining were measured prospectively in radical prostatectomy specimens to determine the incremental improvement in prediction of patient outcome over clinical findings. MATERIALS AND METHODS: From a previous prospective study of 392 consecutive patients with prostate cancer who did not receive preoperative therapy and were treated with radical prostatectomy 25 had pathological stage pT3aN0M0, 24 had pT3bN0M0, 2 had pT2bN1M0, 7 had pT3aN1M0 and 14 had pT3bN1 prostate cancer. These locally advanced stage cases comprise the current study population and further analysis was done with p53 immunostaining. All prostate specimens were totally embedded, serially sectioned and whole mounted. We examined pathological, clinical and laboratory findings as well as p53 immunostaining. RESULTS: Median followup was 5.4 years (range 0.5 to 6.4). Univariate analysis revealed that pathological stage, 10% or greater immunostaining for p53, area and length of extraprostatic cancer extension, and cancer volume (all p </=0.03) were associated with biochemical (prostate specific antigen) or clinical failure. When all variables were considered in stepwise multivariate analysis none attained statistical significance after p53 status entered the model (p <0.01, risk ratio 2.9 for 10% or greater versus less than 10%, 95% confidence interval 1.4-6.2). The concordance index analysis for the predictive ability of prostate specific antigen, stage, grade and ploidy (c = 0.66) was inferior to the predictive ability of a statistical model also including p53 status (c = 0.71). CONCLUSIONS: In cases of locally advanced stage cancer p53 immunoreactivity after radical prostatectomy improves outcome prediction. Addition of this variable to those routinely determined may identify a subset of patients who would benefit from more intensive postoperative surveillance and adjuvant therapy.

Aged↗