Expanded TCRß CDR3 clonotypes distinguish Crohn's disease and ulcerative colitis patients.

We aimed to determine whether the TCR repertoires of Crohn's disease (CD) patients contain highly prevalent disease-specific T-cell clonotypes reflective of the characteristic and highly shared aberrant serum antibody reactivity to gut commensal flagellin antigens. The CD4 TCRß CDR3 sequence repertoires from active CD (n = 20) and ulcerative colitis (UC) (n = 10) patients were significantly more diverse, and individual sequences over-represented, compared to healthy controls (HC) (n = 97). While a very small number of expanded public CDR3 sequences are highly shared between active CD and UC, the majority of significantly expanded TCRß CDR3 clonotypes are private to CD and UC patients with equivalent prevalence among IBD patients. Further defining TCR clonotypes by Vß-CDR3 linkage showed significant differences in the TCR repertoires between UC and CD. Flagellin antigen exposure induced expansion of several TCRß CDR3 sequences in CD4 cells from a flagellin-seropositive subject including sequences highly shared by or relatively private to CD (and UC) patients. These data suggest that flagellin-reactivity contributes to the expansion of a small number of CD4 clonotypes but does not support flagellin antigens as predominantly driving CD4 cell proliferation in CD. Disease-specific expanded TCRß CDR3 clonotypes characterize CD and UC and the shared exposure to the gamut of gut microbial antigens.

Adenocarcinoma of the prostate: an expensive way to die.

The costs of radical prostatectomy and radiation therapy for localized carcinoma of the prostate are well known, the costs of terminal care for men with metastatic disease less so. We sought to determine the costs of terminal care incurred with prostate cancer in the last year of life. A retrospective chart review was conducted at five military medical centers identifying 32 patients who had died from prostate cancer from 1995 to 1997. The data investigated were: duration of metastatic disease, days hospitalized in the last year of life, palliative procedures (surgery or radiation), chemotherapy and need for transfusions. The mean duration of symptomatic metastatic disease was 3.4 y. The mean duration of hospitalization in the last year of life was 19 days. Seven patients (22%) required channel transurethral resection of the prostate (TURP). Three patients (9%) required either percutaneous nephrostomies or stenting. The mean number of transfusions required was 5.4. Eighteen patients (56%) underwent bilateral simple orchiectomy (BSO), 14 (44%) used LHRH agonists and 11 (34%) used anti-androgens. The mean total cost of hospitalization, studies, outpatient visits to physicians, palliative procedures and hormonal therapy was US dollars 24660 in the last year of life. Comparatively, the cost of radical prostatectomy is US dollars 12250 and three-dimensional conformal radiation therapy is US dollars 13823. Our estimation of costs due to metastatic disease is at best an underestimation. Men dying of prostate cancer incur significant costs in the last year of life. Based upon recent epidemiological data the cost of death due to prostate cancer in the US is over three quarters of a billion dollars a year.

Phase II trial of 5-fluorouracil plus eniluracil in patients with advanced pancreatic cancer: a Southwest Oncology Group study.

BACKGROUND: Eniluracil is a potent, irreversible inactivator of dihydropyrimidine dehydrogenase, the major catabolic enzyme for 5-fluorouracil (5-FU). Pretreatment with eniluracil significantly increases plasma half-life, plasma concentration and oral bioavailability of 5-FU. This multicenter phase II trial was designed to estimate the 6-month survival rate in patients with metastatic adenocarcinoma of the pancreas treated with 5-FU and eniluracil. PATIENTS AND METHODS: One hundred and sixteen patients (61 with no prior chemotherapy and 55 with prior chemotherapy) were registered for treatment with eniluracil 50 mg (total dose) p.o. on days 1-7 and 5-FU 20 mg/m(2)/day p.o. on days 2-6 of a 28-day treatment cycle. RESULTS: In 106 patients evaluable for survival, the 6-month survival rate was 34% [95% confidence interval (CI) 22% to 47%, median survival 3.6 months] for patients who had not been treated previously with chemotherapy and 29% (95% CI 16% to 42%, median survival 3.4 months) for those who had received prior chemotherapy. For those patients with measurable disease, the confirmed response rates were 8% and 2%, respectively. The most common grade 3-4 toxicities were neutropenia (29% of patients) and diarrhea (12% of patients). Overall, 69% of patients experienced a grade 3 or worse adverse event during treatment. CONCLUSIONS: These results suggest that the combination of a 7-day course of eniluracil and a 5-day course of oral 5-FU has limited activity in patients with advanced pancreatic cancer, and is associated with a high frequency of clinically significant adverse events.

Correlation of cystoscopic impression with histologic diagnosis of biopsy specimens of the bladder.

There is a paucity of information in the contemporary literature that would permit assessment of the urologist's ability to endoscopically discriminate between benign and malignant lesions of the bladder or to predict the grade and stage of papillary neoplasms. This prospective study evaluates the correlation between cystoscopic impression of urothelial lesions and final histologic diagnoses. Sixty-four patients with 68 urothelial abnormalities requiring formal biopsy or endoscopic resection were evaluated prospectively. At the time of endoscopy, treating urologists completed questionnaires documenting the surgeon's endoscopic impression of disease type and extent and performed standard biopsy or resection of all suspicious lesions. Specimens were submitted for routine histopathologic analysis, and the results were correlated with the questionnaire data. Endoscopic evaluation correctly discriminated between dysplastic/malignant and benign/reactive lesions in this study with a sensitivity of 100%, specificity of 100%, and positive and negative predictive values of 100%. Urologists could not readily distinguish between low- and high-grade papillary urothelial lesions and were frequently unable to determine if a tumor was invasive, particularly if the degree of invasion was microscopic. Endoscopic impression at the time of bladder biopsy or resection is accurate and discriminates between the presence and absence of cancer. Endoscopic impression alone is a relatively poor staging tool with respect to extent of invasive disease and must be coupled with careful histopathologic analysis of biopsy material, bimanual examination when appropriate, and axial imaging for complete assessment of a given tumor.

Phase II evaluation of suramin in advanced renal cell carcinoma. A Southwest Oncology Group study.

Twenty-two eligible patients with advanced renal carcinoma were treated with suramin utilizing a fixed dose regimen. Therapy was reasonably well tolerated with 3 of 22 patients (14%) developing grade 4 toxicity and 11 of 22 patients (50%) having a maximum toxicity of grade 3. There were no responders; median survival was 10 months. Suramin is not an active agent in advanced renal carcinoma.

Prostate cancer in men age 50 years or younger: a review of the Department of Defense Center for Prostate Disease Research multicenter prostate cancer database.

PURPOSE: Prostate cancer in men age 50 years or younger traditionally has accounted for approximately 1% of those diagnosed with prostate cancer. Prior studies of prostate cancer in men of this age led many clinicians to believe that they have a less favorable outcome than older men. Most of these studies were conducted before the advent of prostate specific antigen (PSA) screening programs. We evaluated a surgically treated cohort of men age 50 years or younger to determine whether disease recurred more frequently among them than in those 51 to 69 years old in the PSA era. MATERIALS AND METHODS: We reviewed the medical records of 477 men who underwent radical prostatectomy between 1988 and 1997. Age, ethnicity, preoperative PSA, clinical and pathological stage, margin and seminal vesicle involvement, and recurrence were compared between 79 men age 50 years or younger (study group) and 398, 51 to 69 years old (comparison group). Disease-free survival rates were compared using Kaplan-Meier and Cox regression techniques. RESULTS: There were 6 (7.6%) recurrences in the study group (79) and 107 (26.9%) in the comparison group (398). The disease-free survival curves were significantly different (log-rank p = 0.010). Age remained a significant prognostic factor (Wald p = 0.033) in multivariate Cox regression analyses that controlled for race, clinical and pathological stage, and pretreatment PSA. Similar results were found when the comparison group was limited to 116 patients 51 to 59 years old (log-rank p = 0.034, Wald p = 0.069). CONCLUSIONS: These data suggest that patients in the PSA era who underwent radical prostatectomy and were age 50 years or younger have a more favorable disease-free outcome compared to older men.

Long-term hazard of progression after radical prostatectomy for clinically localized prostate cancer: continued risk of biochemical failure after 5 years.

PURPOSE: Cure from malignancy is commonly defined as a disease-free state lasting 5 years after treatment. We analyzed clinical and biochemical progression rates after radical prostatectomy for men with clinically localized prostate cancer with particular attention to recurrence beyond 5 years. Annual hazard rates of progression were calculated to determine the probability of recurrence at specific intervals following surgery. MATERIALS AND METHODS: The records of 2,782 men with clinically localized prostate cancer (cT1-T2) undergoing radical prostatectomy between 1987 and 1993 were reviewed. All patients were treated in the prostate specific antigen (PSA) era so that serial followup PSA values were available from the time of surgery. Analysis was limited to patients who did not receive adjuvant treatment within 90 days of radical prostatectomy. Disease progression was defined as documented local recurrence, systemic progression and/or PSA 0.4 ng./ml. or greater. Lymph node positive cases were eliminated from analysis since almost all received adjuvant hormonal therapy. Annual hazard rates for progression were calculated using the formula: [No. events / No. patients at risk] x 100. Progression-free survival probabilities were determined using the Kaplan-Meier method. RESULTS: Pathological stage was pT2a-b, N0 (68%), pT3a, N0 (21%) and pT3b, N0 (11%). Biochemical progression-free survival at 5 and 10 years was 76% and 59%, respectively, for the entire study population while those with pathologically organ confined (pT2, N0) cancers had progression-free survival rates of 82% and 68% at 5 and 10 years, respectively. A total of 819 patients (29%) eventually had disease progression, including 160 (6%) with progression after 5 years. Annual hazard rates were highest during the first 2 years after radical prostatectomy for the entire population. Patients with adverse prognostic features (pT3b, PSA 10 ng./ml. or greater, Gleason score 8-10 and nondiploid cancers) had high initial hazard rates that decreased with time to lower levels. Those with pathologically organ confined cancer had low but constant hazard rates throughout followup. CONCLUSIONS: Although progression after radical prostatectomy usually occurs early, reflecting the impact of clinical under staging, a significant number of men, including those with organ confined cancers, will continue to have disease progression after 5 years. Patients undergoing radical prostatectomy should be subjected to long-term followup to allow the option of early intervention should progression occur.

The relationship between early biochemical failure and perineural invasion in pathological T2 prostate cancer.

OBJECTIVES: To evaluate, in patients with pathologically localized prostate cancer, the relationship between early biochemical failure, i.e. an increasing prostate-specific antigen (PSA) level, and perineural invasion (PNI) on final pathology. PATIENTS AND METHODS: The records were reviewed of 171 patients with prostate cancer who underwent prostatectomy at one institution between January 1992 and December 1995. Data on the histology, therapy and PSA level were collected and evaluated. RESULTS: Of the 171 patients with pathologically localized (pT2) prostate cancer, 131 were evaluable; 17 (13%) had a detectable PSA level in the first 5 years after surgery and 63 had PNI in the pathological specimen. Of those with PSA recurrence, 14 had PNI, one had no PNI and in two there was no comment on PNI. In comparison, only 10 of the 17 patients with recurrence had a Gleason sum of >/= 7. CONCLUSION: Perineural invasion seems to be an important predictor of early outcome in patients with organ-confined prostate cancer treated by prostatectomy. In this series it was the most sensitive predictor of biochemical failure. A more detailed pathological evaluation of prostate cancer may allow the clinician to provide closer surveillance and better informed clinical decision-making.

Multicenter patient self-reporting questionnaire on impotence, incontinence and stricture after radical prostatectomy.

PURPOSE: We determined the incidence of patient self-reported post-prostatectomy incontinence, impotence, bladder neck contracture and/or urethral stricture, sexual function satisfaction, quality of life and willingness to undergo treatment again in a large multicenter group of men who underwent radical prostatectomy. We also determined whether the morbidities of sexual function satisfaction, quality of life and bladder neck contracture and/or urethral stricture are predictable from demographic and postoperative prostate cancer factors. MATERIALS AND METHODS: A self-reporting questionnaire was completed and returned by 1,069 of 1,396 eligible patients (77%) who underwent radical prostatectomy between 1962 and 1997. Of the respondents 868 (85.7%) underwent surgery after 1990 and in all prostatectomy had been done a minimum of 6 months previously. Questionnaire results were independently analyzed by a third party for morbidity tabulation and the association of patient reported satisfaction. RESULTS: The patient self-reported incidence of any degree of post-prostatectomy incontinence, impotence and bladder neck contracture or urethral stricture was 65.6%, 88.4% and 20.5%, respectively. The incidence of incontinence requiring protection was 33% and only 2.8% of respondents had persistent bladder neck contracture or urethral stricture. Although incontinence and impotence significantly affected self-reported sexual function satisfaction, quality of life and willingness to undergo treatment again (p = 0.001), 77.5% of patients would elect surgery again. This finding remained true even after adjusting for demographic variables, and the time between surgery and the survey by multiple logistic regression. CONCLUSIONS: Although radical prostatectomy morbidity is common and affects self-reported overall quality of life, most patients would elect the same treatment again. Impotence and post-prostatectomy incontinence were significantly associated with sexual function satisfaction, quality of life and willingness to undergo treatment again. Bladder neck contracture and/or urethral stricture was associated with willingness to undergo treatment again after adjusting for demographic variables and time from surgery to the survey.

Long-term outcome in patients with pTxN+ adenocarcinoma of prostate treated with radical prostatectomy and early androgen ablation.

PURPOSE: We assessed retrospectively the outcome after bilateral pelvic lymphadenectomy and radical prostatectomy for pathological pTxN+ adenocarcinoma of the prostate when treated with or without adjuvant androgen ablation therapy. MATERIALS AND METHODS: A total of 790 men treated with radical prostatectomy for prostatic adenocarcinoma were found to have pTxN+ disease and treated further with or without androgen ablation therapy. Mean patient age was 64 years (range 40 to 79). Mean followup was 6.5 years, (range up to 25). Clinical stages were T2 or less in 60% of the cases, T3 in 38% and N+ in 2%. Gleason scores were 6 or less in 31% and 7 or greater in 69%. Deoxyribonucleic acid ploidy was diploid in 43%, tetraploid in 39% and aneuploid in 18%. Of the patients 96 (12%) received no androgen ablation therapy, with the remainder getting androgen ablation therapy within 90 days of radical prostatectomy. RESULTS: Of the patients 186 (24%) died, with 109 (14%) dying of prostatic anedocarcinoma. Overall (and cause specific) survival probabilities at 5, 10 and 15 years were 87 (91), 69 (79) and 39% (60%), respectively. Patients with diploid tumors had better cause specific survival than those with nondiploid tumors (p = 0.009). Patients with diploid tumors were less likely to have progression biochemically, locally or systemically than those with nondiploid tumors (p = 0.038). Androgen ablation therapy had no effect on cause specific survival in nondiploid patients. Diploid patients treated with androgen ablation therapy for up to 10 years had no improvement in disease specific survival compared to those with no androgen ablation therapy. However, cancer death was significantly reduced after 10 years (p <0.002). The local control rate of pTxN+ cases that receive radical prostatectomy and androgen ablation therapy at 15 years is virtually identical to that of stage pT2c cases at our institution (79 +/- 3.0 versus 80% +/- 3.5%, respectively). There were no deaths secondary to radical prostatectomy, and complications were within the experience of that seen in patients with localized disease. CONCLUSIONS: Radical prostatectomy with androgen ablation therapy is a viable option for patients with pTxN+ disease, particularly in view of excellent local control rates and low morbidity. Patients with diploid tumors have a more favorable outcome than those with nondiploid tumors when treated with androgen ablation therapy.

Army and Air Force leadership in the Prostate Cancer Prevention Trial.

Prostate cancer is now the most common solid tumor in men in the United States. Although the current public health approach to this disease is early diagnosis and treatment, investigations are also focusing on the possibility of disease prevention. The Prostate Cancer Prevention Trial, begun in 1993, has completed recruitment of 18,000 men who will be randomized to receive either finasteride or placebo to determine if finasteride can prevent the development of this disease. Both Army and Air Force institutions are participating in this trial, with four Department of Defense institutions contributing over 10% of the patients randomized. The results of this study may have a major impact on active duty personnel for whom prevention of prostate cancer may become possible.

Pathologic classification of prostate carcinoma: the impact of margin status.

BACKGROUND: A proposed pathologic (pTNM) classification system for prostate carcinoma was analyzed for its impact on survival outcome in the prostate specific antigen (PSA) era. The impact of margin status on the survival outcome of patients with otherwise organ-confined disease (i.e., without extraprostatic extension or seminal vesicle involvement) was assessed. METHODS: Among 5467 patients, the original pathologic classification was T2 in 2094 patients; those with evidence of positive margins, extraprostatic extension, or seminal vesicle involvement were initially classified as having pT3 disease (2920 patients) or pT4 residual disease (211 patients). According to the proposed pTNM system, 1512 patients for whom margin status was considered independent of T classification were reclassified. RESULTS: After reclassification, 803 specimens had been down-classified to pT2, resulting in 2932 (54%) with pT2N0 organ-confined disease and a margin positivity rate of 27%; originally, only 38% of patients had been classified as pT2N0. When the old and new classifications were compared, 5-year progression free survival to the combined endpoint of clinical and/or PSA progression (< or = 0.2 ng/mL) was 86% versus 84% and 70% versus 67% for disease classified as pT2N0 and pT3N0, respectively. Multivariate analysis assessed the effect of margin status on 2334 pT2N0 patients (classified according to the proposed pTNM system) who did not receive adjuvant therapy; adjustments were made for Gleason grade, preoperative PSA, and DNA ploidy. In this analysis, the relative risk (with 95% confidence interval) associated with positive margins was 1.65 (1.24-2.18); this was significant for the combined endpoint of clinical/PSA progression. The 5-year survival, free of clinical/PSA progression, was 86% for those without versus 75% for those with positive margins. CONCLUSIONS: This analysis supports the adoption of the proposed pTNM system, which will allow for uniform reporting of pathologic data on prostate carcinoma. For patients with organ-confined disease, positive margins are associated with higher rates of PSA progression. Accordingly, patients should be stratified based on margin positivity in addition to pT classification.

Will current clinical trials answer the most important questions about prostate adenocarcinoma?

Despite a heightened focus of the medical and research community on prostate cancer, many important questions about this disease remain unanswered. These include questions about the possible prevention of prostate cancer, as well as the optimal treatment approaches for localized, locally advanced, metastatic, and hormone-refractory disease. A whole host of prospective, well-designed clinical trials are currently in progress that should answer many of these questions. This review briefly explores some of these unresolved issues and describes ongoing trials designed to address them.

Expression of human prostate-specific glandular kallikrein protein (hK2) in the breast cancer cell line T47-D.

Human glandular kallikrein (hK2) protein, like prostate-specific antigen (PSA), is produced mainly in prostatic epithelium. It may be useful as a new diagnostic indicator for prostate cancer. Recently, a number of hK2-specific monoclonal antibodies have been developed that enable us to detect hK2 protein in human prostate tissue, seminal fluid, and sera. Whether hK2 can be expressed, like PSA, in nonprostatic cells is not known. In this study, we have characterized the presence of hK2 in an androgen-responsive breast cancer cell line T47-D at both the protein and mRNA levels with an immunoassay, Western blot analysis, Northern blot analysis, and the reverse transcription-PCR. Using a sensitive immunoassay with monoclonal antibodies to hK2, we found that T47-D cells could be induced with androgens, mineralocorticoids, glucocorticoids, and progestins to produce significantly more hK2 than PSA. Estrogens failed to mimic the effect of the other steroids, blocking instead the stimulatory effect of androgens. Androgen induction of hK2 in T47-D cells was dose dependent. More interestingly, we found that the hK2 in androgen-induced T47-D cell spent media appears to be the pro-form of hK2 rather than mature hK2. Our study demonstrates that hK2, a serine protease thought to be found only in prostate-related tissues and fluids, is also produced in a breast cancer cell line T47-D after steroid stimulation. This finding suggests that hK2 may have a potential role in breast cancer as well as prostatic cancer and will be the impetus for further studies of hK2 distribution and function.

The effects of androgen administration on phallic androgen receptor expression.

PURPOSE: Whether androgens down regulate the androgen receptor during penile development is controversial. We investigated the effects of androgens on penile androgen receptor expression. MATERIALS AND METHODS: We injected prepubertal hypogonadotropic hypogonadal microphallic rats with testosterone or dihydrotestosterone. Specimens were obtained at 3 (prepuberty), 9 (puberty to early postpuberty) and 12 weeks (late postpuberty). At necropsy we compared penile size and androgen receptor expression of these animals to those of age matched nontreated hypogonadotropic hypogonadal and normal controls. RESULTS: At age 3 weeks prepubertal androgens up regulated androgen receptor expression and significantly increased penile size compared to normal and untreated hypogonadotropic hypogonadal controls. By 9 weeks the normal down regulation of androgen receptor that occurs with maturation was present. Prepubertal androgens failed to accelerate or exaggerate the normal maturational loss of the androgen receptor. At 9 weeks penile size of normal controls and prepubertal androgen treated animals was identical. Interestingly despite down regulation of the penile androgen receptor, normal animals continued to have increases in penile size between 9 and 12 weeks, while the prepubertal androgen treated animals had no penile growth. CONCLUSIONS: Prepubertal androgen administration in hypogonadotropic hypogonadal animals resulted in diminutive penises in adulthood. However, the decrease in penile size was not associated with an accelerated or exaggerated down regulation of the androgen receptor. This finding coupled with continued growth of the normal control penises after androgen receptor down regulation suggests that cessation of penile growth may not be solely related to down regulation of the penile androgen receptor.

Prostate specific antigen detected prostate cancer (clinical stage T1c): an interim analysis.

PURPOSE: The majority of impalpable prostate cancers (state T1c) are biologically significant. We report the interim results in 257 patients with stage T1c prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: Prostate specific antigen progression-free survival was assessed by the Kaplan-Meier method. Multivariate analyses were performed to determine which clinical and pathological variables independently correlated with progression. Comparisons among the various clinical substages (T1a to T2b/c) were calculated. RESULTS: Of the patients with stage T1c cancers 51% had stage pT2c or less and 91% had clinically significant tumors on the basis of pathological grade, deoxyribonucleic acid ploidy and tumor volume. High preoperative prostate specific antigen, poorly differentiated tumors and nondiploid status were strong independent predictors of progression. The 5-year survival rate free of progression was 84%. Patients with clinical stage T1c cancers had a significant progression-free survival advantage compared to those with clinical stage T2b/c disease (p = 0.0005). CONCLUSIONS: Impalpable tumors should not be regarded as insignificant or innocuous on the basis of pathological analysis. Disease-free survival in the stage T1c group was similar to that in the clinical stages T1a to T2a group but significantly better than that in the T2b/c group.

Inhibition of human transitional cell carcinoma in vitro proliferation by fluoroquinolone antibiotics.

PURPOSE: The in vitro effects of the fluoroquinolone antibiotics ciprofloxacin and ofloxacin upon 3 human transitional cell carcinoma cell lines were investigated at concentrations that are attainable in the urine of patients taking these drugs orally. MATERIALS AND METHODS: Cell lines TCCSUP, T24, and J82 were exposed in culture to either ciprofloxacin or ofloxacin at concentrations ranging from 0 to 800 micrograms./ml. and at durations ranging from 24 to 120 hours. Inhibition of proliferation and DNA synthesis were assessed via MTT and tritiated thymidine assays, respectively. RESULTS: From the MTT assay ciprofloxacin, at concentrations of 25 to 800 micrograms./ml., produced proliferation inhibition in the TCCSUP line ranging from 8.1% to 90.2% at 24 hours, 25.1% to 94.9% at 72 hours, and 53.8% to 96.9% at 120 hours. Inhibition of proliferation for the T24 line ranged from 8.0% to 85%, 31.5% to 96.5%, and 27.3% to 98.2%. Inhibition of proliferation of the J82 line ranged from 20.8% to 84.8%, 22.8% to 92.7%, and 37.4% to 97.1%. Inhibition of DNA synthesis (due to ciprofloxacin at the concentrations above) as measured by the tritiated thymidine assay was also significant for each of the 3 cell lines. Inhibition of proliferation and DNA synthesis due to ofloxacin was lower but not overall statistically different from that due to ciprofloxacin. In a separate experiment, enhanced cytotoxicity was observed at lower concentrations of ciprofloxacin when the initial media pH was approximated to 5.5. CONCLUSIONS: Ciprofloxacin and ofloxacin inhibit proliferation and DNA synthesis of these 3 human TCC lines in vitro. Inhibition occurred in a concentration- and time-dependent manner. The concentrations that were assessed are attainable in the urine of patients taking these agents orally.

Prostate-specific human kallikrein (hK2) as a novel marker for prostate cancer.

BACKGROUND: Although prostate-specific antigen (PSA) has aided significantly in the diagnosis of prostate cancer, more sensitive and accurate assays are needed. Presently, we are developing a sensitive immunoassay for hK2 protein for the detection of prostate cancer. METHODS: Polyclonal and monoclonal antibodies specific for hK2 were produced and used for Western blot analysis and immunohistochemistry for detection of hK2 protein in serum and human tissues. The reverse-transcriptase polymerase chain reaction (RT-PCR) was utilized to detect hK2 mRNA from patient blood samples. RESULTS: Western blot analysis demonstrated that the antibodies used are monospecific for hK2. Immunohistochemistry showed that hK2 is expressed only in prostatic epithelia. An RT-PCR study showed that hK2 mRNA would be a useful candidate for early detection of prostatic micrometastasis. CONCLUSIONS: Monospecific antibodies for hK2 have been developed for detecting hK2 protein. Our studies indicate that hK2 may be a useful marker for prostate cancer.

Incidence of benign and malignant prostate tissue in biopsies of the bladder neck after a radical prostatectomy.

PURPOSE: We determined whether bladder neck sparing radical prostatectomy may leave prostate tissue in the unresected bladder neck. MATERIALS AND METHODS: We intraoperatively evaluated the presence of prostate tissue in bladder neck biopsy specimens from 73 consecutive patients undergoing bladder neck sparing radical prostatectomy. RESULTS: Of the 73 specimens 14 (19%) contained prostate tissue: 9 (12%) were positive for prostate cancer and 5 (7%) contained benign prostate tissue. All patients with a positive bladder neck biopsy had a positive margin at another site. CONCLUSIONS: We recommend routine bladder neck biopsies for patients undergoing a bladder neck sparing procedure.