Isolation and characterization of the major form of human MUC18 cDNA gene and correlation of MUC18 over-expression in prostate cancer cell lines and tissues with malignant progression.

Ectopical expression of huMUC18, a cell adhesion molecule in the immunoglobulin gene superfamily, causes a non-metastatic human melanoma cell line to become metastatic in a nude mouse system. To determine if MUC18 expression correlates with the development and malignant progression of prostate cancer, we investigated differential expression of human MUC18 (huMUC18) in normal prostate epithelial cells, prostate cancer cell lines, and prostatic normal and cancer tissues. We cloned and characterized the human MUC18 (huMUC18) cDNA gene from three human prostate cancer cell lines and three human melanoma cell lines. The cDNA sequences from the six human cancer cell lines were identical except differences in one to five nucleotides. The deduced amino acid sequences of the longest ORF were 646 amino acids that were identical in these cDNAs except for one to three amino acid residues. The amino acid sequences of all our huMUC18 cDNA genes are similar to that cloned by other group (GenBank access #M28882) except differences in the same seven amino acids. We conclude that huMUC18 cDNA gene reported here represents the gene product from a major allele. The MUC18 mRNA and protein was expressed in three metastatic prostate cancer cell lines (TSU-PR1, DU145, and PC-3), but not in one non-metastatic prostate cancer cell line (LNCaP.FGC). The expression of huMUC18 in these four cell lines is positively related to their extent of in vitro motility and invasiveness and in vivo metastasis in nude mice. HuMUC18 protein was also expressed at high levels in extracts prepared from tissue sample sections containing high grade prostatic intraepithelial neoplasia (PIN), but weakly expressed in extracts prepared from cultured primary normal prostatic epithelial cells and the normal prostate gland. Immunohistochemical analysis showed that huMUC18 was expressed at higher levels in the epithelial cells of high-grade PIN and prostatic carcinomas, and in cells of a perineural invasion, a lymph node, and a lung metastases compared to that in normal or benign hyperplastic epithelium (BPH). We therefore conclude that MUC18 expression is increased during prostate cancer initiation (high grade PIN) and progression to carcinoma, and in metastatic cell lines and metastatic carcinoma. Increased expression of MUC18 is implicated to play an important role in developing and malignant progression of human prostate cancer. Furthermore, the lacking of predominant cytoplasmic membrane expression of MUC18 appeared to correlate with malignant progression of prostate cancer.

Accumulation of mitochondrial DNA deletions in the malignant prostate of patients of different ages.

It has been shown that mitochondrial DNA (mtDNA) deletion mutations accumulate with age in many tissues of the body. However, to date no one has shown that these deletions occur in the malignant prostate. Therefore, we hypothesize that such deletions do occur in the prostate and increasingly so with advanced age. To test this hypothesis, DNA was isolated from 34 radical prostatectomy specimens, and the entire mitochondrial genome (16.5kb) was amplified using long range PCR (LXPCR). The LXPCR products were visualized by gel electrophoresis, and the presence of low molecular weight (<16kb) bands was considered evidence of large mtDNA deletions. In order to show that these lower molecular weight LXPCR bands were not simply PCR artifact, we also digested mtDNA from a subset of the same patients and did Southern analysis with a mtDNA probe. Southern blots confirmed the existence of large deletions in every sample tested. Furthermore, several of the specific deletions identified by LXPCR were also seen in the Southern blots. From the LXPCR data, we found that as the age of the specimen increased, so did the average number of low molecular weight bands (i.e. deletions). In particular, one prominent band was seen at 1.2kb and became more consistent with advanced age.

Methoxypsoralen phototherapy of transitional cell carcinoma.

OBJECTIVES: The goal of this research was to assess whether methoxypsoralen compounds in combination with ultraviolet light were effective in preventing cellular proliferation in an in vitro model of human transitional cell carcinoma. METHODS: Three methoxypsoralen compounds, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 4'-aminomethyl 4,5'-8'-trimethylpsoralen (AMT), were added in vitro to T-24 transitional cell carcinoma cells. Psoralens directly bind to DNA, cross-linking the strands when exposed to ultraviolet light and thereby prevent cellular division. RESULTS: In vitro activity was demonstrated utilizing AMT and ultraviolet radiation at 320 to 340 nm, preventing cellular proliferation in T-24 transitional cell carcinoma. CONCLUSIONS: Methoxypsoralen compounds in combination with ultraviolet light are effective in preventing proliferation of bladder carcinoma cells in vitro. This therapy may prove to be effective in clinical early stage transitional cell carcinoma and warrants further assessment.

Intravesical suramin in the prevention of transitional cell carcinoma.

OBJECTIVES: To examine the effects of intravesical suramin on N-methyl-N-nitrosurea (MNU)-induced bladder tumors in Fischer 344 rats. METHODS: Multiple cohorts of female rats received four biweekly intravesical instillations of MNU. A control group received no other treatment, the experimental group received 25 mg/kg intravesical suramin twice a week beginning at week 6. RESULTS: After 18 weeks from the first instillation of MNU, 60% to 65% of control animals developed papillary transitional cell carcinoma, compared with only 0% to 10% of the suramin-treated animals (P = 0.01 to P = 0.0007). There was no local or systemic toxicity observed. CONCLUSIONS: Intravesical suramin is an effective chemopreventative therapy for transitional cell carcinoma in vivo with minimal toxicity.

Normal range prostate-specific antigen versus age-specific prostate-specific antigen in screening prostate adenocarcinoma.

OBJECTIVES: Prostate-specific antigen (PSA) has become the most useful serum tumor marker in the diagnosis and screening of prostate adenocarcinoma. The currently cited reference range of normal (0 to 4.0 ng/mL monoclonal) lacks both the sensitivity and specificity to be universally accepted as a screening test, and alternatives to serum PSA have been proposed, such as PSA density, PSA velocity, and age-adjusted PSA. Age-adjusted PSA takes into account the facts that as men grow older the prostate enlarges and that screening should have maximum sensitivity in younger men and maximum specificity in older men. METHODS: A population of 4,710 men with no known history of prostate adenocarcinoma underwent 5,629 examinations by transrectal ultrasound of the prostate (TRUS) from 1987 to 1994. This population consists of Mobile Urology Group, Mobile, Alabama, and Emory University, Atlanta, Georgia, patient databases. We have examined our data to determine the sensitivity, specificity, and positive predictive values for normal range PSA (0 to 4 ng/mL) versus age-specific PSA values. RESULTS: A total of 2040 patients had an abnormal digital rectal examination (DRE) and 3581 procedures were performed for an elevated PSA and a normal DRE. Biopsies were performed in 2,657 patients with 945 (35.6%) positive for cancer. Criteria for biopsy included elevated PSA (more than 4 mg/mL), PSA density more than 0.15 abnormal DRE, or suspicious TRUS. Patients were grouped according to decade: group 1 (ages 40 to 49 years, n = 183), group 2 (ages 50 to 59 years, n = 1018), group 3 (ages 60 to 69 years, n = 2358), and group 4 (ages 70 to 79 years, n = 1687). CONCLUSIONS: Use of the age-specific range for PSA increases the sensitivity in younger men more likely to benefit from treatment, and decreases the biopsy rate in older patients who may not be candidates for aggressive treatment. Age-adjusted PSA is the most valuable for patients over the age of 70 years of whom 22% would be spared TRUS with biopsy.

Evaluation of staging lymphadenectomy in prostate cancer.

OBJECTIVES: To prospectively evaluate a clinical algorithm that predicts nodal status in patients with prostate cancer and to assess the impact on the outcome. METHODS: Between September 1988 and December 1994, 192 patients with organ-confined prostate cancer and considered surgical candidates for radical perineal prostatectomy (RPP) were stratified using the algorithm: prostate-specific antigen (PSA) 20 ng/mL or less, Gleason score 7 or lower, and clinical Stage T2a or lower. Patients failing any of these criteria were placed in the high-risk group and underwent a pelvic lymphadenectomy. Patients who satisfied all the criteria were placed in the low-risk group and underwent RPP without evaluation of the pelvic lymph nodes. Another contemporaneous cohort of patients (n = 65) underwent pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) without use of the algorithm and were used as a control group. Patients were monitored for at least 24 months. RESULTS: In the RPP group, 177 patients were considered low risk according to the algorithm and were not offered staging lymphadenectomy before surgery, whereas 15 patients were categorized as high risk for metastasis and underwent staging lymphadenectomy. In the RRP and lymphadenectomy group, 41 patients were considered at low risk and 24 at high risk of disease spread according to the algorithm. In the RPP group, low-risk patients (no lymphadenectomy) had a PSA recurrence rate (27%) similar to that of low-risk patients in the RRP group with negative lymph nodes (29%), P = 0.8. Similarly, high-risk patients with negative lymph nodes in both groups had a similar recurrence rate (53% for RPP and 50% for RRP). Univariate logistic regression analysis showed that PSA was the most significant predictor for disease recurrence (P = 0.0004) followed by preoperative Gleason scores (P = 0.02) and clinical stages (P = 0.03). Multivariate stepwise analysis demonstrated that Gleason score and clinical stage did not add to the prediction of recurrence over PSA alone. CONCLUSIONS: Staging lymphadenectomy can be omitted in low-risk patients without deleterious effects on the outcome as measured by PSA recurrence.

Serum PSA after antiandrogen therapy.

Patients who present with advanced prostate cancer and who are treated with primary endocrine therapy have a significantly longer time to progression and a clear survival advantage if their serum PSA concentration normalizes. The prognostic significance of normalization of PSA is independent of other prognostic measures. Normalization of serum PSA at month 3 is the earliest and most highly correlated predictor of response. Most patients (80%-85%) who have disease progression while on hormonal therapy will show a rising PSA 6 to 12 months before other clinical findings become abnormal. A rising PSA in the hormonally treated patient, even if the values are within the "normal" range, signals impending clinical progression. These patients should be considered for second-line hormonal therapies or alternative salvage protocols, as a theoretically favorable window of opportunity may exist when the PSA begins to rise. Patients treated with second-line therapies should also undergo serial PSA measurements; those responding with an 80% to 90% decrease in serum PSA are statistically more likely to enjoy a prolonged response.

Expression of progranulin and the epithelin/granulin precursor acrogranin correlates with neoplastic state in renal epithelium.

BACKGROUND: Current traditional pathological parameters, including staging and grading, are not sufficient in predicting outcome in patients with renal cell carcinoma (RCC). Acrogranin is an epithelial growth factor and has been demonstrated to play a role in teratocarcinogenesis and tumorigenesis. The aim of this study was to examine levels of acrogranin in renal cancer. MATERIALS AND METHODS: Western blot analysis was performed on renal tissue protein lysates. In addition, immunohistochemical (IHC) analysis of acrogranin expression was conducted on tissue sections of various histological types and grades of RCC. RESULTS: Western analysis showed that acrogranin levels were low in benign renal tissue and increased in malignant renal tissue. In addition, IHC revealed that high-grade RCC exhibited higher levels of expression than low-grade RCC and normal tissue. CONCLUSION: These data suggest that acrogranin may be a functional important growth factor in RCC and may be a potential molecular marker for high-grade RCC.

Advances in molecular classification of renal neoplasms.

Kidney neoplasms are classified by light microscopy using the World Health Organization (WHO) system. The WHO system defines histopathologic tumor subtypes with distinct clinical behavior and underlying genetic mutations. In adults, the common malignant subtypes are variants of renal cell carcinoma (RCC). Histopathologic classification is critical for clinical management of RCC, but is becoming more complex with recognition of novel tumor subtypes, development of procedures yielding small diagnostic biopsies, and emergence of molecular therapies directed at tumor gene activity. Therefore, classification systems based on gene expression are likely to become essential for diagnosis, prognosis and treatment of kidney tumors. Recent DNA microarray studies have shown that clinically relevant renal tumor subtypes are characterized by distinct gene expression profiles, which are useful for discovery of novel diagnostic and prognostic biomarkers. In this review, we summarize the WHO classification system for renal tumors, general applications of microarray technology in cancer research, and specific microarray studies that have advanced knowledge of renal tumor diagnosis, prognosis, therapy and pathobiology.

Antegrade approach to radical retropubic prostatectomy in patients with difficult apical dissection.

Among 335 radical retropubic prostatectomies an antegrade dissection was used in 30 because of difficulty in developing the usual planes of dissection during apical dissection. The adequacy of tumor resection, preservation of sexual potency and urinary continence were compared in patients who underwent the antegrade dissection and those who underwent the standard retrograde nerve-sparing radical retropubic prostatectomy. Histopathological evaluation revealed no significant difference in the over-all completeness of tumor excision between the group having an antegrade dissection (16 of 30, 53% completely excised) and those having a retrograde dissection (177 of 305, 58% completely excised) (p = 0.62). Patients with clinically localized but pathological stage C disease undergoing an antegrade dissection and a nerve-sparing procedure had a significantly higher incidence of positive lateral margins (9 of 12, 75%) than the comparable group undergoing a retrograde dissection (40 of 99, 40%) (p = 0.02). The incidence of positive apical margins was similar in both groups, with 5 of 14 (36%) of the antegrade stage C cases (36%) having positive apical margins compared to 37 of 117 of the retrograde stage C cases (32%) (p = 0.65). Sexual potency was preserved in 5 of 6 patients (83%) treated with an antegrade dissection who had both neurovascular bundles preserved and were followed for at least 6 months, compared to 86 of 142 (61%) who underwent retrograde dissection (difference not significant, p = 0.26). Potency was preserved in 6 of 13 evaluable patients (46%) undergoing unilateral antegrade nerve-sparing procedure compared to 21 of 48 evaluable patients (44%) undergoing unilateral retrograde nerve-sparing procedure (p = 0.88). Of 22 patients followed for 1 year 21 (95%) have regained urinary continence. We conclude that the antegrade approach to radical retropubic prostatectomy provides results that are comparable to those achieved with the standard retrograde approach but that when an antegrade approach is chosen because of periprostatic fibrosis, bilateral preservation of the neurovascular bundles may result in a higher incidence of positive surgical margins.

Lower incidence of unsuspected lymph node metastases in 521 consecutive patients with clinically localized prostate cancer.

Between 1983 and 1991 we saw 521 consecutive patients who elected to undergo radical prostatectomy for clinically localized prostatic carcinoma. We performed staging pelvic lymphadenectomy to avoid radical prostatectomy in patients with pelvic lymph node metastases who would be unlikely to be cured by the operation. However, we found that significantly fewer patients had lymph node metastases than historical reports would have led us to predict. Of 32 patients with clinical stage A1 disease none had positive nodes, compared to 2 of 61 (3.3%) with stage A2, 10 of 189 (5.3%) with stage B1 and 23 of 236 (9.7%) with stage B2 disease. We conclude that this lower incidence of nodal involvement relative to previous reports reflects a true change in the stage at which prostate cancer currently is diagnosed. We postulate that a higher index of suspicion, earlier detection, more aggressive intervention to establish the diagnosis, use of ultrasound guided prostate biopsies and more widespread screening for prostate cancer contribute to the lower incidence of occult lymph node metastases in patients with clinically localized prostate cancer.

Clinical features and management of anterior intraurethral prostatic cyst.

We report on a symptomatic anterior intraurethral prostatic cyst in a 46-year-old man without clinical evidence of benign prostatic hyperplasia. The anterior location of this cyst makes it unique to all previously reported cases of prostatic cysts which are located posteriorly. Transurethral resection of the cyst with limited resection of the anterior prostatic tissue at the base of the cyst was performed with successful resolution of voiding symptoms. In the absence of lateral lobe hypertrophy, standard transurethral resection of the prostate should be avoided to ensure preservation of erectile and ejaculatory function.

Cell-mediated immunity to tumor-associated antigens is a better predictor of survival in early stage breast cancer than stage, grade or lymph node status.

Cell-mediated immune (CMI) responses to tumor-associated antigens (TAA) in the early postoperative period were examined for correlations with disease recurrence and survival in a 13-year-prospective study of 77 stage 1 and 2 breast cancer patients treated with modified radical or radical mastectomy alone. Among the 21 patients who had positive lymphoproliferative tests using patients' peripheral blood mononuclear cells and autologous TAA of breast cancer cells, only one died from metastatic disease (5%). Among the 56 patients who had a negative test, 23 died from metastatic disease (41%). This difference is statistically significant (p = 0.002) Three other risk factors including tumor size, nodal status and cell differentiation patterns were also analyzed. When these three clinical-pathologic criteria were analyzed individually, none reliably predicted disease recurrence and survival. Nodal status was the most predictive clinical-pathologic risk factor, but was not significant (p = 0.089). The results of this study demonstrate the detection of CMI responses against autologous TAA by lymphoproliferative assays identifies a sub-set of stage 1 and 2 breast cancer patients who are at minimal risk of developing metastatic disease. This testing also identifies immunologically unreactive patients who are at risk for disease recurrence.

Staging pelvic lymphadenectomy for prostate cancer: a comparison of laparoscopic and open techniques.

The operative morbidity and convalescence of our initial 30 patients who underwent laparoscopic pelvic lymph node dissections were compared to those of 16 patients who underwent open surgical pelvic lymph node dissections performed at our institution for staging purposes between 1990 and 1992. The average time for laparoscopic pelvic lymph node dissection (199.4 minutes) was nearly twice that of surgical pelvic lymph node dissection (102.4 minutes). However, the blood loss in the former group was significantly less. Oral intake occurred after a mean of 0.63 days in the laparoscopic pelvic lymph node dissection group compared to 2.87 days in the surgical group. Also, laparoscopic pelvic lymph node dissection was superior to surgical pelvic lymph node dissection in terms of average postoperative analgesic use (1.55 versus 47 mg. morphine sulfate), average hospital stay (1.7 versus 5.37 days), average return to normal daily activities (4.94 versus 42.9 days) and interval to full recovery (10.8 versus 65.5 days). However, the incidence of significant complications in the laparoscopic pelvic lymph node dissection group was 13%, with no complications seen in the surgical group. Interestingly, all significant problems in the bilateral laparoscopic pelvic lymph node dissection patients were confined to our initial 12 patients, indicating the steepness of the laparoscopic learning curve.

Correlation of testicular color Doppler ultrasonography, physical examination and venography in the detection of left varicoceles in men with infertility.

High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes. To define the ability of color Doppler ultrasound to detect clinically evident as well as subclinical varicoceles men referred to our urology division with oligospermia and infertility underwent spermatic vein venography of the left testis if there was physical examination and/or color Doppler ultrasound evidence of a varicocele. The detection of valvular incompetence on venography was considered diagnostic for a varicocele. Of 17 study patients physical examination detected 10 of 14 venographically evident varicoceles (71%), whereas color Doppler ultrasound detected 13 of 14 (93%). Of 5 patients with a normal physical examination but with color Doppler ultrasound evidence of a varicocele 4 had a confirmatory venogram, and 1 of 2 patients with a varicocele on physical examination and a normal Doppler ultrasound had a positive venogram. These data suggest that color Doppler ultrasound of the testis may more appropriately direct further invasive testing and therapy of infertile men than physical examination alone.

Quantitative study of electroporation-mediated molecular uptake and cell viability.

Electroporation's use for laboratory transfection and clinical chemotherapy is limited by an incomplete understanding of the effects of electroporation parameters on molecular uptake and cell viability. To address this need, uptake of calcein and viability of DU 145 prostate cancer cells were quantified using flow cytometry for more than 200 different combinations of experimental conditions. The experimental parameters included field strength (0.1-3.3 kV/cm), pulse length (0.05-20 ms), number of pulses (1-10), calcein concentration (10-100 microM), and cell concentration (0.6-23% by volume). These data indicate that neither electrical charge nor energy was a good predictor of electroporation's effects. Instead, both uptake and viability showed a complex dependence on field strength, pulse length, and number of pulses. The effect of cell concentration was explained quantitatively by electric field perturbations caused by neighboring cells. Uptake was shown to vary linearly with external calcein concentration. This large quantitative data set may be used to optimize electroporation protocols, test theoretical models, and guide mechanistic interpretations.

Glutathione S-transferase pi gene methylation: the search for a molecular marker of prostatic adenocarcinoma.

Glutathione S-transferase pi gene methylation has recently been described in prostatic adenocarcinoma. Aggregate data on 115 samples studied to date have found an 87% sensitivity and 92% specificity for prostate cancer diagnosis. The current literature about this new marker is herein summarized, and possible molecular mechanisms by which glutathione S-transferase pi may participate in prostatic carcinogenesis are reviewed. The possible clinical implications of this molecular alteration in the diagnosis of prostatic adenocarcinoma are also studied.

Epidermal growth factor (EGF) and EGF receptor in hypospadias.

OBJECTIVE: To determine whether alterations in epidermal growth factor (EGF), which plays a major role both in the masculinization of the genitourinary tract and in wound healing, or EGF receptor (EGFR) expression are associated with hypospadias. PATIENTS AND METHODS: The prepuces from 22 children undergoing circumcision (median age 27 months, range 5-87) and skin biopsies from 16 children undergoing surgery for hypospadias (median age 12 months, range 3-57) were studied. Fourteen patients had distal, one had mid-shaft and one had penoscrotal hypospadias. Immunoperoxidase staining was carried out for EGF and EGFR and the density of the staining quantified using image cytometry by an operator unaware of the diagnosis. RESULTS: The median EGF density in foreskins obtained by circumcision was 75% (mean 73, SE 2.1) compared with 54% (mean 52, SE 3.9) for tissue samples from patients with hypospadias (P < 0.001); the mean EGFR was similar in both materials. CONCLUSION: The mean EGF value was deficient in skin adjacent to hypospadias defects compared to normal phallic skin, suggesting that the inadequate expression of EGF may be related to the aetiology of hypospadias and to possible wound complications following surgery for hypospadias.

A prospective study of transperineal prostatic block for transurethral needle ablation for benign prostatic hyperplasia: the Emory University Experience.

PURPOSE: We evaluate the feasibility, effectiveness and role of transperineal prostate block in providing anesthesia during minimally invasive radio frequency thermal therapy of the prostate. MATERIALS AND METHODS: A total of 38 consecutive patients undergoing transurethral needle ablation for symptomatic benign prostatic hyperplasia were entered in this prospective study. All patients received transperineal prostatic block as the main method of anesthesia. A mixture of equal volumes of 1% lidocaine and 0.25% bupivacaine, each with epinephrine (1:100,000 concentration ratio) was used. Pain control during the instillation of transperineal prostatic block and transurethral needle ablation was assessed using a 10-point linear analog pain scale and questionnaire. RESULTS: Median patient age was 65.5 years (range 47 to 79), with 21% of men in the eighth decade of life. Median American Urological Association symptom score was 25.0 (range 14 to 35), bother score was 20.0 (11 to 28), quality of life score was 4.0 (3 to 6) and peak urinary flow rate was 8.9 cc per second (3.5 to 15.7). Median sonographic prostate volume was 35.0 cc (range 17 to 129). Median volume of anesthetic agent used was 40.0 cc (range 30 to 60) per case (1.1 cc solution per 1 cc prostate tissue). No adverse events were encountered. Median pain score was 3.3 (range 1 to 6) during instillation of transperineal prostatic block and 1.0 (0 to 6) during transurethral needle ablation. Transperineal prostatic block proved highly effective and was a satisfactory method of anesthesia during transurethral needle ablation as judged by postoperative questionnaire. No sedation, narcotic or analgesia was required. All procedures were performed in the outpatient cystoscopy suite or office setting without support of an anesthesia team or conscious sedation monitoring. CONCLUSIONS: Transperineal prostatic block is a safe, convenient, effective and satisfactory method of minimally invasive anesthesia for transurethral needle ablation of the prostate in an outpatient office setting. Elderly patients and those at high surgical risk can be treated safely using this approach. Considerable cost saving is seen secondary to omission of charges related to anesthesia team support, recovery room facility and conscious sedation monitoring.

Poor prognosis associated with thrombocytosis in patients with renal cell carcinoma.

OBJECTIVES: To better define the relationship between platelet count and survival using a retrospective analysis in patients with thrombocytosis and metastatic renal cell carcinoma (RCC), some of whom had a shorter life expectancy than those with a normal platelet count. PATIENTS AND METHODS: The records were reviewed of patients with stage IV RCC who had undergone a variety of adjuvant therapies after nephrectomy between 1972 and 1992. Entry criteria included a tissue diagnosis of RCC, at least one platelet count and a complete follow-up until the time of death. Of 350 patients available for review, 259 met the entry criteria. Patients were divided into two groups: group 1 included 112 patients whose platelet counts remained at < 4 x 105/microL between the time of nephrectomy and the time of death; group 2 included 147 patients with at least one platelet count of > 4 x 105/microL (mean age in each group 57 years). RESULTS: The mean (SD) survival for group 1 was 151 (34) months, compared with 92 (18) months for those in group 2. Using the log-rank chi-square test the difference in survival between the groups was significant (P = 0.005). Controlling for established prognostic indicators of pathological stage, nuclear grade and cell type, using Cox's regression technique, the difference in survival between the groups remained significant (P = 0.015). CONCLUSIONS: These results suggest that patients with metastatic RCC who receive adjuvant therapy and have a persistently normal platelet count have a 64% longer life expectancy than those with thrombocytosis. The difference is highly statistically significant when controlled for nuclear grade, cell type and pathological stage.