Validation of a food frequency questionnaire measurement of selected nutrients using biological markers in African-American men.

OBJECTIVE: To validate selected nutrients assessed by the food frequency questionnaire (FFQ) used in the Harvard cohort studies in an African-American group. DESIGN: Blood aliquots were pooled for each decile of intake of two carotenoids and alpha tocopherol as measured by FFQ. These pooled samples were analyzed for nutrient content, and the resultant blood levels were plotted against the median for each decile of intake. In addition, adipose tissue samples taken from each man were analyzed for content of specific fatty acids. We calculated the Spearman correlations comparing intakes of specific fatty acids as percent of total fat intake, adjusted for energy intake, as measured by FFQ, with the percentage of the corresponding fatty acid in adipose tissue. SUBJECTS AND SETTINGS: African-American men (N=104) with prostate cancer were recruited from a Detroit physician's practice and completed a detailed FFQ. RESULTS: Comparing decile 10 with decile 1 intake of nutrients as measured by FFQ, there was a 32% higher blood level of lycopene, a 288% higher blood level of beta carotene and a 100% higher blood level of alpha tocopherol. The Spearman correlation coefficients between intakes of linoleic acid, alpha linolenic acid, long-chain n-3 fatty acids and trans fatty acid measured by FFQ and the corresponding adipose tissue levels were between 0.10 and 0.47. CONCLUSION: The FFQ was able to distinguish meaningful differences in biochemical measurements of selected nutrients and presumably corresponding differences in the extremes of intake in African-American men with prostate cancer who were likely to be motivated to report accurately. However, the results found are similar to those found in other populations.

A common nonsense mutation in EphB2 is associated with prostate cancer risk in African American men with a positive family history.

BACKGROUND: The EphB2 gene was recently implicated as a prostate cancer (PC) tumour suppressor gene, with somatic inactivating mutations occurring in approximately 10% of sporadic tumours. We evaluated the contribution of EphB2 to inherited PC susceptibility in African Americans (AA) by screening the gene for germline polymorphisms. METHODS: Direct sequencing of the coding region of EphB2 was performed on 72 probands from the African American Hereditary Prostate Cancer Study (AAHPC). A case-control association analysis was then carried out using the AAHPC probands and an additional 183 cases of sporadic PC compared with 329 healthy AA male controls. In addition, we performed an ancestry adjusted association study where we adjusted for individual ancestry among all subjects, in order to rule out a spurious association due to population stratification. RESULTS: Ten coding sequence variants were identified, including the K1019X (3055A-->T) nonsense mutation which was present in 15.3% of the AAHPC probands but only 1.7% of 231 European American (EA) control samples. We observed that the 3055A-->T mutation significantly increased risk for prostate cancer over twofold (Fisher's two sided test, p = 0.003). The T allele was significantly more common among AAHPC probands (15.3%) than among healthy AA male controls (5.2%) (odds ratio 3.31; 95% confidence interval 1.5 to 7.4; p = 0.008). The ancestry adjusted analyses confirmed the association. CONCLUSIONS: Our data show that the K1019X mutation in the EphB2 gene differs in frequency between AA and EA, is associated with increased risk for PC in AA men with a positive family history, and may be an important genetic risk factor for prostate cancer in AA.

Reduction of QM protein expression correlates with tumor grade in prostatic adenocarcinoma.

The QM protein is a transcription cofactor inhibiting the activity of AP-1 transcription factors and is also a ribosomal protein participating in protein synthesis. While protein synthesis is known to be increased in many cancers, inhibition of AP-1 activity presumably suppresses development and growth of sex-hormone-regulated tumor cells. The present study is the first report on immunohistochemical data of QM in human prostatic tissues. Paraffin sections of human prostate cancer samples were immunohistochemically stained for QM. The staining scores were analyzed with the clinicopathologic data of the patients. QM protein expression was found in all normal prostate glands adjacent to prostate cancer and in various intraepithelial neoplasia (PIN). In prostate cancer, the staining intensity and stained areas were decreased, compared to the normal glands and PIN lesions; in high-grade tumors only some patches of tumor cells showed positivity. Intense (3+) staining was mostly observed in the Gleason grade three areas (48%) compared to grade 4 and 5 areas (22%), although both low and high-grade tumors showed similar percentages of weakly stained areas. Moreover, staining in prostatic adenocarcinoma was often topographically patchy and varied from negative or weak (1+) to intense (3+). There was an inverse correlation from normal to low-grade tumors and then to high-grade tumors. However, in high-grade tumors, the positive areas were mostly confined to peripheral aspects of tumors and were particularly strong in foci of perineural invasion. This preliminary study suggests that decreased QM expression may be associated with early development of prostate cancer, but later a high level of QM may facilitate progression of the tumors to a more aggressive phenotype.

Fluorescence in situ hybridization analysis of 8p allelic loss and chromosome 8 instability in human prostate cancer.

Cytogenetic and molecular biological studies have demonstrated deletion of sequences that map to the short arm of chromosome 8 (8p) in tumors from several organ systems, including sequences that map within or near 8p22 in human prostate tumors. Recent studies in our laboratory have suggested that deletion of sequences on 8p may be concurrent with alterations in dosage for chromosome 8. In order to further investigate this finding, the present study has applied fluorescence in situ hybridization (FISH) techniques to determine the status of chromosome 8 in prostate tumors that have undergone deletion of sequences at 8p22. Dosage of 8p22 sequences was assayed utilizing unique sequence cosmid DNA probes by FISH and confirmed by amplification of microsatellite sequences by polymerase chain reaction (PCR). Chromosome 8 dosage was assayed by FISH utilizing both unique sequence cosmid probe DNA (specific to the 8q13.1-q13.3 chromosomal region) and pericentromeric probe DNA. FISH analysis of 10 specimens of normal or benign prostatic hyperplasia tissues paired with 9 tumor and one prostatic intraepithelial neoplasia tissues from the same patients for dosage at 8p, 8cen, and 8q, and PCR analysis for dosage at 8p, demonstrated that (a) FISH provided a more precise means of evaluating allelic loss than PCR in prostate tissue; (b) 8p22 sequence losses occurred frequently in prostate tumors; (c) 8p22 sequence losses were most often detected in the absence of 8cen or 8q sequence dosage alterations, although they were sometimes accompanied by gain or loss of 8cen or 8q sequences; and (d) the pattern of 8p22 sequence losses was most often widespread rather than focal. This study is the first to describe FISH analysis of interphase nuclei within tissue sections using cosmid probe DNAs.

Evidence for three tumor suppressor gene loci on chromosome 8p in human prostate cancer.

Allelic loss of human chromosome sequences is often equated with inactivation of putative tumor suppressor genes. Loss of sequences on the short arm of chromosome 8 (8p) has been observed in human cancers, especially of 8p22 in prostate tumors. By using PCR analysis of highly polymorphic microsatellite repeat markers at nine 8p loci in 135 tumors, we observed deletion of sequences at 8p22 and at two other proximal deletion domains. These novel deletion domains encompass the NEFL locus and D8S87-ANK1 loci, respectively. These data suggest that three 8p tumor suppressor gene loci may be independently deleted in human prostate cancers.

Localization of potential tumor suppressor loci to a < 2 Mb region on chromosome 17q in human prostate cancer.

We recently demonstrated a high frequency of loss of heterozygosity (LOH) at the D17S856 and D17S855 (within the BRCA1 gene) loci in primary prostate cancer, suggesting that the BRCA1 gene and/or other tumor suppressor gene(s) located within the interval of the D17S856 and D17S855 loci and/or within the vicinity of this interval may be important in prostate cancer (Cancer Res., 55: 1002-1005, 1995). To further define the exact boundary of the deleted region (i.e., D17S856/D17S855) and to detect other possible LOH regions on the long arm of chromosome 17, we analysed 23 matched normal and tumor DNAs with 15 polymorphic microsatellite markers spanning chromosome 17q12-21. Eleven of 22 (50%) informative tumors showed allelic deletion at one or more of the loci studied. A minimal area of LOH was identified to extend from the proximal boundary at the D17S776 locus to the distal boundary at the D17S855 locus, spanning an estimated < 2 Mb segment on chromosome 17q21. Our results suggest that a potential tumor suppressor gene(s) may reside in the < 2 Mb region centromeric (inclusive) to the BRCA1 gene and that this tumor suppressor gene(s) may be involved in the formation of prostate cancer.

8pter-p23 deletion is associated with racial differences in prostate cancer outcome.

Deletions of chromosome sequences mapping to the short arm of chromosome 8 have been observed frequently in a variety of human cancers. A small number of studies have suggested that the terminal portion of the short arm of chromosome 8, 8pter-p23, may be deleted independently of other portions of 8p in human tumors, and that deletion of the 8pter-p23 region may be correlated with poor prognosis. The aim of the present study was to physically define the minimal region of 8pter-p23 deletion and to define the frequency and prognostic significance of 8pter-p23 loss in human prostate tumors. DNA was purified from normal and tumor tissues of 45 radical prostatectomy specimens and amplified for 15 highly polymorphic microsatellite sequences, 13 spanning 8pter-p23 and 2 proximal 8p markers. Allelic loss of 8p sequences was observed in 28 of 45 (62%) tumors examined. Of these, approximately half (12 of 28; 43%) demonstrated independent loss of the 8pter-p23 region, with several tumors defining a 5-cM minimal region of deletion spanning D8S264-D8S1824-D8S1781-D8S262-D8S1798. When serum prostate-specific antigen was used as a surrogate end point marker for survival, 8pter-p23 loss was significantly associated with reduced disease-free progression (log-rank P = 0.0426). Moreover, loss of the 8pter-p23 region was significantly associated with poor survival for American Caucasian (log-rank P = 0.0024) but not African-American (log-rank P = 0.5832) prostate cancer patients. These studies suggest that independent deletion of 8pter-p23 is differentially associated with disease recurrence and poor outcome in American Caucasian but not African-American prostate cancer patients.

A similar pattern of chromosomal alterations in prostate cancers from African-Americans and Caucasian Americans.

A combination of genetic and epigenetic factors may explain the disproportionate incidence and mortality of prostate cancer among African-American males (AAMs) as compared with Caucasian American males (CAMs). We wished to determine whether primary prostate cancers from AAMs and CAMs harbor different patterns or frequencies of chromosomal alterations. Comparative genomic hybridization (CGH) was performed on clinically localized, untreated primary prostate cancers from 16 AAMs and 16 CAMs. Detailed statistical analysis was used to delineate gains and deletions with high sensitivity and specificity and to compare the frequency and pattern of alterations between the two groups of tumors. The two groups of patients had indistinguishable preoperative serum prostate-specific antigen levels, and the two groups of tumors had similar pathological stages and grades. Chromosomal gains and deletions occurred in regions known to be frequently altered in prostate cancer. Specifically, the most frequent alterations were deletions of regions on chromosomes 13q, 5q, 16q, and 8p and gains of regions on 8q and 5q. When tumors from AAMs and CAMs were compared, the frequencies of alteration (deletion, gain, or no alteration) were similar across 98.9% of the length of the genome. The patterns of alterations of the most frequently altered chromosomes were also similar between tumors from AAMs and CAMs. We concluded that primary prostate cancers from AAMs and CAMs harbor a similar pattern and frequency of chromosomal alterations. These data support the notion that sporadic prostate cancers from AAMs and CAMs develop by similar chromosomal mechanisms. Biological differences, if present, do not occur on the chromosomal level.

Defining the extent and nature of cytogenetic events in prostatic adenocarcinoma: paraffin FISH vs. metaphase analysis.

A comparative study of primary prostatic tumors utilizing conventional metaphase analysis of prostate tumor cultures and fluorescence in situ hybridization (FISH) analysis of paraffin-embedded tissue sections revealed significant differences in type and extent of cytogenetic aberrations. Clonal trisomy 7 was identified in two tumors by metaphase analysis of prostate cultures, but not confirmed in either case by FISH analysis. True gain of chromosome 8 was revealed by FISH analysis in malignant epithelium of four tumors but not in adjacent normal or hyperplastic glands. Neither gain nor loss of this chromosome was observed by metaphase analysis in any of the tumors. Significant monosomy and nullisomy of chromosome 10 was identified in one case by FISH, but no cells with gain or loss of chromosome 10 were observed by metaphase analysis. Significant loss of the Y chromosome was revealed in one tumor by FISH, but no cells with -Y were identified by metaphase analysis. Clonal loss of the Y chromosome was identified in two other tumors by metaphase analysis. Paraffin FISH analysis of these tumors revealed overall monosomy in both, although in one tumor there was extensive nodular loss of the Y chromosome. Paraffin FISH analysis permits identification of cytogenetic aberrations in areas identified as carcinoma (CaP), prostatic intraepithelial neoplasia (PIN), and benign prostatic hyperplasia (BPH). This technique appears more informative in defining the true extent and nature of cytogenetic aberrations in prostate cancer than metaphase analysis of prostate tumor cultures.

Cytogenetics of primary prostatic adenocarcinoma. Clonality and chromosome instability.

We have examined 62 prostatic adenocarcinomas by conventional cytogenetic analysis. Most were primary cultures harvested in 14 days or less. The most consistent finding was a normal male diploid karyotype, found in 87% of all cells analyzed, and as the exclusive finding in 19 tumors. Nonrandom chromosomal changes included gain of chromosome 7 and loss of the Y chromosome. In addition, clonal gains of chromosomes 8, 12, and 18, and clonal losses of chromosomes 14 and 19 were noted in individual cases. Two structural clonal aberrations, a 9p+ in one case and a t(Y;22) (q11.2;p12) in another, were also seen. Ten of 62 cultures demonstrated chromosome instability, defined herein as nonclonal gain or loss of chromosomes in more than 10% of the metaphases examined from that culture. In those cases with nonclonal numerical aberrations, loss of chromosomes was more common than gain. The distribution of apparently random numeric abnormalities was similar to that of the clonal abnormalities in that the most frequent nonclonal gain was of chromosome 7 and the most frequent nonclonal loss was of the Y chromosome. Apparently random structural aberrations were observed in less than 1% of all analyzed cells. These included a 4p-,del(3)(q13), and t(1;11). The extent of apparently random aneuploidy suggests that chromosome instability characterizes cultured prostatic adenocarcinomas. An increase in the frequency of nonclonal aberrations may be an indicator of tumor origin in a predominantly diploid cell population. The coexistence of clonally aberrant, nonclonally aberrant, and normal diploid cells in culture may reflect heterogeneity of prostate tumors in vivo.

A new approach in the diagnosis and follow-up of bladder cancer. FISH analysis of urine, bladder washings, and tumors.

The aim of the present study was to ascertain whether fluorescence in situ hybridization (FISH) of urine could be a useful approach in bladder cancer. Herein, we present the cytogenetic and FISH findings in patients with and without bladder cancer. The samples examined with FISH consisted of urine, bladder washings, and tumor tissue, when available. The results obtained show that the FISH technique, particularly when used on urine, is a very useful tool in the diagnosis, early detection, and management of bladder cancer.

Removal of the financial barrier to health care: does it impact on prostate cancer at presentation and survival? A comparative study between black and white men in a Veterans Affairs system.

OBJECTIVES: African-American men are known to have a higher incidence and mortality rate from prostate cancer than American-Caucasian men. It is also known that African Americans have a higher incidence of advanced stage disease at diagnosis. One hypothesis for the latter is a delay in diagnosis due to lack of financial access to health care. Because eligibility for medical care in Veterans Affairs Medical Centers (VAMCs) is similar for both black and white patients, less disparity of stage at diagnosis, and therefore survival between blacks and whites, would be expected. METHODS: Cases for this study included only those histologically confirmed, newly diagnosed prostate cancers at the Allen Park VAMC in Wayne County, Michigan, between 1973 and 1992. Trained Surveillance, Epidemiology, and End Result (SEER) abstractors determined the stage at diagnosis, according to SEER criteria. Data analyses include descriptive statistics and survival analysis. RESULTS: The distribution of race and annual income of all male patients seen at the VAMC in Allen Park is similar. Over the entire 20-year period (1973 to 1992), there were a total of 358 prostate cancers in white patients and 383 in black patients. The ages of black and white patients were comparable. The proportion of white and black men presenting with localized disease is similar (57% and 54%, respectively). A significantly greater proportion of black patients with prostate cancer were classified as having distant disease compared with white patients (25% versus 19%; P = 0.045). A racial "crossover" effect in survival occurred around age 70 years, with white men demonstrating improved survival under 70 years of age, and black men 70 years and older tending to have better survival. CONCLUSIONS: These data suggest that financial access to care has no apparent influence on the higher proportion of distant disease and poorer survival of African-American patients with prostate cancer compared with American-Caucasian men.

A comparison of the W-stapled ileal reservoir with hand-sewn reservoirs for orthotopic bladder replacement.

OBJECTIVES: Confidence has increased in the use of an orthotopic reservoir to the urethra after a cystoprostatectomy for bladder cancer; however, many surgeons would welcome a method to simplify the operative procedure. The availability of absorbable staples on a GIA stapler allows study of the incorporation of stapling procedures into formation of a reservoir. Because of the success of hand-sewn W-configured ileal reservoirs, we initiated a Phase II study to evaluate absorbable staples in formation of a W-configured reservoir. We now present an expanded contemporary series comparing a W-stapled ileal neobladder with hand-sewn ileal (Studer) or hand-sewn ileocolic (Le Bag) reservoirs. METHODS: Forty-five selected patients underwent orthotopic urinary diversion after cystoprostatectomy for bladder cancer (n = 42) or prostate cancer (n = 3) using one of the three methods of reservoir construction. There were 43 men and 2 women. The evaluation included a urodynamic evaluation and a questionnaire sent to patients inquiring about urinary function. RESULTS: Most patients did well with the W-stapled ileal reservoir but 6 of 19 evaluable patients had unsatisfactory reservoir characteristics. Three patients needed an augmentation cystoplasty and 3 had higher pressure, smaller volume reservoirs. Reservoir function appeared to be consistently more favorable in patients with either of the hand-sewn reservoirs using an ileal or ileocolic segment. CONCLUSIONS: Although the W-stapled ileal reservoir is safe and allows reservoir formation quickly, the inconsistencies of the results discourage its use in the particular configuration described. Failure of the reservoir to distend could be a function of reservoir design, areas of ischemia in the reservoir, or reaction to staple material. Absorbable staples on the GIA instrument may work satisfactorily for formation of an ileocolic reservoir for continent cutaneous diversion. However, the W-configured orthotopic reservoir as constructed using absorbable staples in this study is inferior to a hand-sewn ileal or ileocolic neobladder.

The predictive value of race as a clinical prognostic factor among patients with clinically localized prostate cancer: a multivariate analysis of positive surgical margins.

OBJECTIVES: Several investigators have reported that African-American men with clinically localized prostate cancer have poorer survival than do white men. In addition, prostate cancer in African-American men is commonly diagnosed at a more advanced stage of disease. Is race or ethnicity predictive of outcome of clinically localized prostate cancer? It has been reported that the presence of positive surgical margins significantly influences time to progression independently of other prognostic factors. Therefore, we have elected to conduct a multivariate analysis of clinical factors including race as potential predictors of positive surgical margin outcome. METHODS: We studied 369 consecutive men (120 African-American and 249 white) who had radical prostatectomies at a single institution. Comparisons by race of Gleason score, stage, presence of positive surgical margins, and mean preoperative prostate-specific antigen (PSA) level were carried out. RESULTS: Our data demonstrate that African-American men have more pathologically locally advanced prostate cancer than do white American men: 69% among blacks compared with 57% among whites. However, the difference in rate of positive surgical margins between blacks and whites is statistically significant: 58% among blacks versus 40% among whites (P = 0.002). Four factors were predictive of positive surgical margins: preoperative PSA level, race, clinical stage, and Gleason score. CONCLUSIONS: We have demonstrated that race is an independent predictor of positive surgical margins among patients with clinically localized prostate cancer and should be included in treatment decisions. In addition, the risk of positive surgical margins increases noticeably when PSA is greater than 10 ng/mL.

Value of preoperative PSA in predicting pathologic stage of patients undergoing salvage prostatectomy.

OBJECTIVE: To evaluate the relationship of prostate-specific antigen (PSA) levels and pathologic stage in patients with prostate cancer treated with radiation therapy and undergoing salvage radical prostatectomy. METHOD: Retrospective analysis of preoperative PSA levels and final pathology in 24 men undergoing salvage prostatectomy following prior radiation therapy. RESULTS: Although preoperative PSA values were significantly higher in patients with positive surgical margins, preoperative PSA levels failed to predict the presence of absence of extracapsular extension, seminal vesicle involvement, or lymph node metastasis. CONCLUSION: Our results suggest that PSA is not a reliable method of accurately predicting the pathologic stage of patients who are candidates for salvage radical prostatectomy.

Impact of location and multifocality of positive surgical margins on disease-free survival following radical prostatectomy: a comparison between African-American and white men.

OBJECTIVES: Although the rate of positive surgical margins is higher in African-American men (AAM) than in white men (WM), the impact of this difference on survival is not clear. Furthermore, it is unknown whether there are racial differences in the distribution of the positive surgical margins after radical retropubic prostatectomy (RRP). We investigated the differences between AAM and WM in terms of the site and multifocality of the positive surgical margins and their effect on disease-free survival (DFS) following RRP. METHODS: Between January 1991 and December 1995, 493 patients (288 WM and 205 AAM) were treated with RRP as monotherapy. Positive surgical margins were observed in 179 patients (86 WM and 93 AAM). Patients were divided in two groups: group 1 = WM and group 2 = AAM. The incidence and location of the positive surgical margins and their correlation with DFS were determined and compared. RESULTS: Overall, AAM had a higher rate of positive surgical margins than WM (48% versus 33%, respectively, P = 0.001). There was no significant difference in the frequency of multifocality of the positive margins (P = 0.4). Positive surgical margins were located significantly more often at the base in AAM (P = 0.015); however, the location of the positive surgical margins did not impact on DFS between groups. In those with multifocal positive surgical margins, AAM had a worse DFS compared with WM (P = 0.03). CONCLUSIONS: Race is an independent prognostic factor for DFS in patients with positive surgical margins. There were no differences in DFS between WM and AAM based on the margin location. In WM, prognostic factors for DFS in those with positive surgical margins were preoperative serum prostate-specific antigen, Gleason score, and pathologic stage. Conversely, in AAM none of these parameters were significant predictors of failure.

Population-based study of pelvic lymph node positivity in clinically localized prostate cancer: a study comparing African Americans and whites.

OBJECTIVES: To evaluate the correlation between race and lymph node metastasis for prostate cancer by analyzing which preoperative parameters may predict lymph node status in both races. METHODS: We analyzed a group of patients (552 American white men [AWM] and 423 African-American men [AAM]) who underwent radical prostatectomy plus modified pelvic lymphadenectomy between January 1991 and June 1997. Patients who received neoadjuvant radiation or hormone therapy were excluded. Univariate and multivariate analyses were performed to determine the influence of race on lymph node positivity, as well as to correlate the preoperative parameters (serum prostate-specific antigen [PSA], biopsy Gleason score, and clinical stage) with lymph node metastasis for each race separately. RESULTS: The AAM presented with significantly higher preoperative Gleason scores and PSA levels than AWM. However, comparing lymph node status by race, the difference of positivity (41 AWM [7.4% and 22 AAM [5.2%]) was not statistically significant (P = 0.16). The percentage of positive nodes was similar in both races for each subset of PSA, Gleason score, and clinical stage. Despite the statistical significance of the three preoperative parameters in univariate analysis, in multivariate analysis only PSA and Gleason score were independent predictors of positive lymph nodes. CONCLUSIONS: There is no influence of race on lymph node metastasis, despite AAM presenting with higher preoperative Gleason scores and PSA levels. In multivariate analysis, preoperative Gleason score and PSA were independent factors for positive nodes regardless of race.

Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer.

OBJECTIVES: Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in males in the United States. The mortality is due mainly to distant metastasis. Therefore, predicting the prognosis of prostate cancer patients is an important clinical problem. Previously, we demonstrated that a 12-lipoxygenase (12-LOX) metabolite of arachidonic acid, 12(S)-hydroxyeicosatetraenoic acid, enhances the invasiveness of prostate cancer cells and that a 12-LOX-selective inhibitor [N-benzyl-N-hydroxy-5-phenylpentanamide] reduces experimental metastasis in animal model systems. In this study, we investigated the potential of 12-LOX as a predictor for the aggressiveness of prostate cancer. METHODS: The mRNA expression level of 12-LOX in 122 matching prostate normal and cancerous tissues were measured by quantitative reverse transcription- polymerase chain reaction. Possible association between 12-LOX expression and histologic grade, pathologic and clinical stage, margin positivity, age, and race was analyzed. RESULTS: 12-LOX mRNA levels were elevated in cancer cells and the expression associated with poor differentiation and invasiveness of prostate cancer. Overall, 46 (38%) of 122 evaluable patients showed elevated levels of 12-LOX mRNA in prostate cancer tissues compared with the matching normal tissues. A statistically significantly greater number of cases were found to have an elevated level of 12-LOX among T3, high grade, and surgical margin-positive than T2, intermediate, and low grade, and surgical margin-negative prostatic adenocarcinomas. CONCLUSIONS: Our data suggest that elevation of 12-LOX mRNA expression occurs more frequently in advanced stage, high-grade prostate cancer and that 12-LOX may serve as an indicator for progression and prognosis of prostate cancer. This enzyme also may be a novel target for the development of anti-invasive and antimetastatic agents.

Prostate cancer and African-American men.

Mortality from prostate cancer is two to three times greater among African-American men between the ages of 50 and 70 than among American Caucasian men of similar ages. Also, African-Americans tend to present with more advanced tumors than their American Caucasian counterparts. This article explores differences between the two races that may account for the disproportionately high mortality among African-Americans and their more advanced disease stage at presentation. These include epidemiologic and histologic features of prostate cancer; clinical, biologic, and environmental factors; and barriers to health care. Various important issues that warrant further investigation are also highlighted.

Early detection issues of prostate cancer in African American men.

There were 35,000 deaths from prostate cancer estimated in 1993. The mortality rate among African American men from prostate cancer is 2-3 times higher than among Caucasian Men between the ages of 50-70. There may be many reason for this disproportionate mortality such as a genetic basis, diet or a difference in doubling time between the ethnic groups. Differences in access to care has also been suggested as a cause for this difference. But what has been clearly demonstrated is that African Americans are diagnosed with prostate cancer at a more advanced stage. Thus, health seeking barriers that delay the diagnosis of prostate cancer until cure or long-term quality survival is no longer possible, may be a primary reason for this disproportionate mortality. Since a higher percentage of African Americans present with advanced and remote prostate cancer, it seems reasonable to focus our attention on programs directed towards early detection of prostate cancer in this high risk population. However there are several controversies associated with early detection such as its benefit, over-treatment, and cost. Perhaps the investigation and resolution of these issues should begin in a high risk population.