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David Grignon

Publications and source records attributed to David Grignon.

17 recordsLinked to original sources
PubMed2006

Results of a phase II trial of transrectal ultrasound-guided permanent radioactive implantation of the prostate for definitive management of localized adenocarcinoma of the prostate (radiation therapy oncology group 98-05).

PURPOSE: To evaluate the effectiveness of transrectal ultrasound-guided permanent radioactive (125)I implantation of the prostate for organ-confined adenocarcinoma of the prostate compared with historical data of prostatectomy and external beam radiotherapy within a cooperative group setting. METHODS AND MATERIALS: Patients accrued to this study had histologically confirmed, locally confined, adenocarcinoma of the prostate with clinical Stage T1b, T1c, or T2a, no nodal or metastatic disease, prostate-specific antigen level of < or =10 ng/mL, and Gleason score of < or =6. All patients underwent transrectal ultrasound-guided radioactive (125)I permanent seed implantation into the prostate. The prescribed dose was 145 Gy to the prostate planning target volume. RESULTS: A total of 27 institutions accrued a total of 101 patients to this protocol, with no institution accruing >8 patients. Six patients were ineligible, leaving 95 properly entered as eligible in the study. The median follow-up was 5.3 years (range, 0.4-6.5 years). At 5 years, 5 patients had local failure, 1 had evidence of distant failure, and 6 (6%) had biochemical failure. The overall survival rate at 5 years was 96.7%. At last follow-up, no patient had died of prostate cancer or related toxicities. Eight patients had a maximal acute toxicity level of 3, and no patient had Grade 4 or 5 acute toxicity. During follow-up, 2 patients had maximal Grade 3 toxicity, both related to bladder issues, and no patient experienced Grade 4 or 5 toxicity. CONCLUSION: The results of this clinical protocol (a multi-institutional trial of brachytherapy for localized adenocarcinoma of the prostate) have demonstrated that this type of trial can be successfully completed through the Radiation Therapy Oncology Group. Biochemical disease-free survival was comparable with other brachytherapy published series and with the results after surgery and external beam radiotherapy.

Adenocarcinoma↗
PubMed2006

Whole-pelvis, "mini-pelvis," or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in the Radiation Therapy Oncology Group 9413 trial.

PURPOSE: The Radiation Therapy Oncology Group (RTOG) 9413 trial demonstrated a better progression-free survival (PFS) with whole-pelvis (WP) radiotherapy (RT) compared with prostate-only (PO) RT. This secondary analysis was undertaken to determine whether "mini-pelvis" (MP; defined as > or = 10 x 11 cm but < 11 x 11 cm) RT resulted in progression-free survival (PFS) comparable to that of WP RT. To avoid a timing bias, this analysis was limited to patients receiving neoadjuvant and concurrent hormonal therapy (N&CHT) in Arms 1 and 2 of the study. METHODS AND MATERIALS: Eligible patients had a risk of lymph node (LN) involvement > 15%. Neoadjuvant and concurrent hormonal therapy (N&CHT) was administered 2 months before and during RT for 4 months. From April 1, 1995, to June 1, 1999, a group of 325 patients were randomized to WP RT + N&CHT and another group of 324 patients were randomized to receive PO RT + N&CHT. Patients randomized to PO RT were dichotomized by median field size (10 x 11 cm), with the larger field considered an "MP" field and the smaller a PO field. RESULTS: The median PFS was 5.2, 3.7, and 2.9 years for WP, MP, and PO fields, respectively (p = 0.02). The 7-year PFS was 40%, 35%, and 27% for patients treated to WP, MP, and PO fields, respectively. There was no association between field size and late Grade 3+ genitourinary toxicity but late Grade 3+ gastrointestinal RT complications correlated with increasing field size. CONCLUSIONS: This subset analysis demonstrates that RT field size has a major impact on PFS, and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of > 15%.

Adult↗
PubMed2006

Characterization of pancreatic lesions from MT-tgf alpha, Ela-myc and MT-tgf alpha/Ela-myc single and double transgenic mice.

In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgf alpha mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgf alpha-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-tgf alpha-ES lines, TGF alpha transgene was expressed mainly in proliferating ductal cells. Ela-myc transgenic mice with a mixed C57BL/6, SJL and FVB genetic background developed pancreatic tumors at 2-7 months of age, and half of the tumors were ductal adenocarcinomas, similar to what was reported originally by Sandgren et al 1. However, in 20% of the mice, the tumors metastasized to the liver. MT100/Ela-myc and MT-tgf alpha-ES/Ela-myc double transgenic mice developed not only acinar carcinomas and mixed carcinomas as previously reported but also various ductal-originated lesions, including multilocular cystic neoplasms and ductal adenocarcinomas. The double transgenic tumors were more malignant and metastasized to the liver at a higher frequency (33%) compared with the Ela-myc tumors. Sequencing of the coding region of p16ink4, k-ras and Rb cDNA in small numbers of pancreatic tumors did not identify mutations. The short latency for tumor development, the variety of tumor morphology and the liver metastases seen in Ela-myc and MT-tgf alpha/Ela-myc mice make these animals good models for investigating new therapeutic and preventive strategies for pancreatic cancer.

Journal Article↗
PubMed2006

Loss of heterozygosity and microsatellite instability at the Xq28 and the A/G heterozygosity of the QM gene are associated with ovarian cancer.

The QM gene is located at Xq28 of the X chromosome. QM may act as a tumor suppressor and may also participate in the 60S ribosomal subunit assembly. We studied loss of heterozygosity (LOH) and microsatellite instability (MSI) of microsatellite markers DXS15A, DXS1107, WI12360 and WI9327 for the Xq28 region in 29 ovarian cancer biopsies. The results showed that the LOH frequencies were 18.2%, 30%, 26.3% and 20.8% for WI12360, WI9327, DXS1107 and DXS15A, respectively, whereas the MSI rates were 18.2%, 50.0%, 31.6% and 12.5%, respectively. All tumors showed LOH or MSI for at least one of these markers. Sequencing the QM cDNA did not identify any mutation other than the adenine (A)/guanine (G) replacement at the 605th nucleotide which changes the coding from serine to asparagine. In 17 (58.6%) of the 29 tumors, both A and G types of QM mRNA were detected, indicating that the QM was A/G heterozygous and escaped X-inactivation. However, cDNA and genomic DNA sequencing revealed that the adjacent normal tissues showed the A/G heterozygosity in only 3 of the 17 cases, while in the remaining 14 cases, four had no more adjacent tissue available and ten revealed either G or A at the 605th nt, indicating an A/G point mutation in these tumors. The allele distribution was 32.8% for the A and 67.2% for the G type QM gene. The frequencies of A/A, G/G and A/G homo- or hetero-zygosity were 3.5%, 37.9% and 58.6%, respectively in cancer tissues but they were 26.1%, 52.2% and 21.7%, respectively in the adjacent tissues, indicating a higher heterozygous rate in cancer (58.6% vs 21.7%, p < 0.01). These results suggest that high frequencies of LOH and MSI at the Xq28 and of the A/G heterozygosity at the 605th nt of the QM gene may be associated with ovarian cancer.

Breast Neoplasms↗
PubMed2005

Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: a report from the Radiation Therapy Oncology Group.

PURPOSE: Erb-1 (epidermal growth factor receptor, EGFR) and Erb-2 (Her-2) are two of the best characterized members in the EGFR pathway. In many tumor types, overexpression of these proteins is associated with enhanced malignant potential. Our objective in this study was to investigate the clinical relevance of EGFR and Her-2 expression in bladder cancer cases from four prospective Radiation Therapy Oncology Group (RTOG) bladder preservation trials using cisplatin-containing chemoradiation (RTOG 8802, 8903, 9506, and 9706). METHODS AND MATERIALS: Tumors from 73 cases from patients with muscle-invading T2-T4a bladder cancers had slides interpretable for EGFR staining; 55 cases had slides interpretable for Her-2 staining. Additionally, the respective prognostic values of p53, pRB, and p16 immunostaining were concomitantly examined. Staining and interpretation of staining were done in a blinded manner, without knowledge of clinical outcome. Staining was judged as positive or negative. Subsequently, staining was correlated with clinical outcome. RESULTS: On univariate analysis, EGFR positivity was significantly associated with improved overall survival (p = 0.044); disease-specific survival (DSS) (p = 0.042); and DSS with intact bladder (p = 0.021). There was also a trend for association between EGFR expression and reduced frequency of distant metastasis (p = 0.06). On multivariate analysis adding tumor stage, tumor grade, whether a visibly complete transurethral resection of bladder tumor (TURBT) was done or not, and patient age to the model, EGFR positivity was significantly associated with improved DSS. On univariate analysis, Her-2 positivity was significantly associated with reduced complete response (CR) rates (50% vs. 81%, p = 0.026) after chemoradiation which remained significant on multivariate analysis. The other markers examined in this study were not found to have any prognostic value in this setting. CONCLUSION: Epidermal growth factor receptor expression appears to correlate significantly with improved outcome in bladder cancer, whereas Her-2 expression is significantly associated only with reduced CR rates after chemoradiation. Further investigations are warranted into how EGFR family members regulate response to chemoradiation in bladder cancer and their potential therapeutic implications.

Analysis of Variance↗
PubMed2005

Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31.

PURPOSE: Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT). METHODS AND MATERIALS: Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression. RESULTS: Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm. CONCLUSION: In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival. The improvement in survival appeared preferentially in patients with a Gleason score of 7-10.

Aged↗
PubMed2005

Androgen suppression plus radiation versus radiation alone for patients with stage D1/pathologic node-positive adenocarcinoma of the prostate: updated results based on national prospective randomized trial Radiation Therapy Oncology Group 85-31.

PURPOSE: To update the effect of immediate androgen suppression in conjunction with standard external-beam irradiation versus radiation alone on a group of histologically lymph node-positive patients with adenocarcinoma of the prostate. MATERIALS AND METHODS: A national prospective randomized trial (Radiation Therapy Oncology Group 85-31) of standard external-beam irradiation plus immediate androgen suppression versus external-beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate. One hundred seventy-three patients in this trial had histologically involved lymph nodes. Ninety-eight patients received radiation plus immediate androgen suppression (luteinizing hormone-releasing hormone [LHRH] agonist), whereas 75 patients received radiation alone with hormonal manipulation instituted at the time of relapse. RESULTS: With a median follow-up of 6.5 years for all patients and 9.5 years for living patients, estimated progression-free survival with prostate-specific antigen (PSA) level less than 1.5 ng/mL at 5 and 9 years was 54% and 33%, respectively, for patients who received immediate LHRH agonist versus 10% [corrected] and 4% for patients who received radiation alone with hormonal manipulation instituted at time of relapse (P < .0001). Multivariate analysis revealed radiation therapy and immediate hormonal manipulation as having a statistically significant impact on all end points analyzed: absolute survival, disease-specific failure, metastatic failure, and biochemical control with PSA less than 4 ng/mL and less than 1.5 ng/mL. CONCLUSION: Pending the results of randomized trials, patients with adenocarcinoma of the prostate who have pathologically involved pelvic lymph nodes (pathologic node-positive or clinical stage D1) should be considered for external-beam irradiation plus immediate hormonal manipulation rather than radiation alone with hormone manipulation at the time of relapse.

Adenocarcinoma↗
PubMed2004

Differential expression of thromboxane synthase in prostate carcinoma: role in tumor cell motility.

Arachidonic acid metabolism through cyclooxygenase, lipoxygenase, or P-450 epoxygenase pathways can generate a variety of eicosanoids. Thromboxane synthase (TxS) metabolizes the cyclooxygenase product, prostanglandin H(2), into thromboxane A(2) (TXA(2)), which can cause vessel constriction, platelet activation, and aggregation. Here we demonstrate that human prostate cancer (PCa) cells express enzymatically active TxS and that this enzyme is involved in cell motility. In human PCa cell lines, PC-3, PC-3M, and ML-2 cells expressed higher levels of TxS than normal prostate epithelial cells or other established PCa cell lines such as DU145, LNCaP, or PPC-1. We cloned and sequenced the full-length TxS cDNA from PC-3 cells and found two changes in the amino acid residues. Immunohistochemical analysis of tumor specimens revealed that expression of TxS is weak or absent in normal differentiated luminal, or secretory cells, significantly elevated in less differentiated or advanced prostate tumors, and markedly increased in tumors with perineural invasion. TxS expressed in PC-3 cells was enzymatically active and susceptible to carboxyheptal imidazole, an inhibitor of TxS. The biosynthesis of TXA(2) in PC-3 cells was dependent on COX-2, and to a lesser extent, COX-1. Treatment of PC-3 cells with a COX-1 selective inhibitor, piroxicam, reduced TXA(2) synthesis by approximately 40%, while the COX-2 specific inhibitor NS398 reduced TXA(2) production by approximately 80%. Inhibition of TxS activity or blockade of TXA(2) function reduced PC-3 cell migration on fibronectin, while having minimal effects on cell cycle progression or survival. Finally, increased expression of TxS in DU145 cells increased cell motility. Our data suggest that human PCa cells express TxS and that this enzyme may contribute to PCa progression through modulating cell motility.

Amino Acid Sequence↗
PubMed2004

Pathogenesis of invasive micropapillary carcinoma: role of MUC1 glycoprotein.

Invasive micropapillary carcinoma, a tumor with highly infiltrative characteristics is defined by a distinctive cleft formation around the neoplastic cell clusters which is presumably a result of the detachment of the cells from the stroma due to as yet undetermined factors. Ultrastructural examination performed on a handful of cases demonstrated an unexpected secretory activity in the stroma-facing surface of the cells. MUC1 is a glycoprotein typically expressed in the apical surface of normal epithelial cells, responsible for maintaining lumen formation. In conventional adenocarcinomas, MUC1 expression is largely intracytoplasmic, intercellular, or apical (in glandular areas). The MUC1 expression pattern was investigated by immunohistochemical staining in invasive micropapillary carcinoma of breast (n=11), pancreas (n=5), gynecologic tract (n=11) and urinary bladder (n=10). The results were contrasted with the staining pattern in conventional carcinomas of the same organs (n=202). In all invasive micropapillary carcinoma, MUC1 expression was predominantly in the stroma-facing surface of the cell clusters (basal), accentuating the outlines of the micropapillary units by forming a distinct band on this surface. In conventional carcinoma the labeling was mostly apical in areas with lumen formation and intracytoplasmic and intercellular in the poorly differentiated areas. In conclusion, in the micropapillary pattern of invasive carcinoma, the expression of MUC1, is largely limited to the basal surface of the cells in contrast to conventional carcinomas in which MUC1 is largely apical, intracytoplasmic or intercellular. This provides support for the reversal of cell orientation as an important factor of the morphogenesis and possibly the pathogenesis of invasive micropapillary carcinoma. Since MUC1 is known to have a role in lumen formation, and has an inhibitory role in the cell to stroma interaction, it is conceivable that it is a key factor in the detachment of cells from stroma allowing for the dissection of the connective tissue and easing the spread of cells.

Adenocarcinoma↗
PubMed2003

Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02.

PURPOSE: Radiation Therapy Oncology Group (RTOG) Protocol 92-02 was a randomized trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD with external-beam radiotherapy (RT) in patients with locally advanced prostate cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL. PATIENTS AND METHODS: Patients received a total of 4 months of goserelin and flutamide, 2 months before and 2 months during RT. A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes. Patients were randomly assigned to receive no additional therapy (short-term [ST]AD-RT) or 24 months of goserelin (LTAD-RT); 1,554 patients were entered onto the study. RESULTS: The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival (OS; 80.0% v 78.5% at 5 years, P =.73), compared with the STAD-RT arm. In a subset of patients not part of the original study design, with tumors assigned Gleason scores of 8 to 10 by the contributing institutions, the LTAD-RT arm had significantly better OS (81.0% v 70.7%, P =.044). There was a small but significant increase in the frequency of late radiation grades 3, 4, and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm (2.6% v 1.2% at 5 years, P =.037), the cause of which is not clear. CONCLUSION: The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason scores 8 to 10, LT adjuvant AD resulted in a survival advantage.

Adenocarcinoma↗
PubMed2003

Race and survival of men treated for prostate cancer on radiation therapy oncology group phase III randomized trials.

PURPOSE: We assessed the impact of race on survival in men treated with external beam radiotherapy with or without hormonal therapy for localized prostate cancer in Radiation Therapy Oncology Group randomized trials. MATERIALS AND METHODS: Between 1975 and 1992, 2,048 men were treated for clinically localized prostate cancer in 1 of 4 consecutive prospective phase III randomized trials. After excluding nonblack and nonwhite men 2,012 remained for analysis. Patients were included in this analysis if they were deemed evaluable and eligible for the trial, and followup information and centrally reviewed pathological results were available. Short-term hormonal therapy consisted of goserelin acetate and flutamide administered 2 months before and during radiotherapy. Long-term hormonal therapy consisted of adjuvant goserelin acetate, which was generally given for 2 years or more. Pretreatment prostate specific antigen (PSA) findings were available in 430 cases (21%), including 213 treated with radiotherapy alone, 60 treated with short-term hormonal therapy and 157 on long-term hormonal therapy. Mean pretreatment PSA was 68.8 and 35.2 ng./ml. in black and white patients, respectively. Cox proportional hazards models were used to identify the impact of previously defined risk groups on overall and disease specific survival. Multivariate analysis was done for the significance of race using a stratified Cox model. Median followup in patients treated in early and late studies exceeded 11 and 6 years, respectively. RESULTS: On univariate analysis black race was associated with lower overall and disease specific survival (p = 0.04, RR = 1.24 and p = 0.016, RR = 1.41, respectively). After adjusting for risk group and treatment type (with or without short-term or long-term hormonal therapy) race was no longer associated with outcome (p >0.05). The trend for a persistent difference in survival was likely due to the higher tumor burden in black men, as reflected in higher PSA. CONCLUSIONS: As previously reported, tumor grade (Gleason score), palpation T stage, lymph node status, pretreatment PSA and treatment type are major predictors of overall and disease specific survival. We noted no evidence that race has independent prognostic significance in patients treated for prostate cancer in Radiation Therapy Oncology Group prospective randomized trials.

Black or African American↗
PubMed2003

Novel perspective: focusing on the X chromosome in reproductive cancers.

In an XX female, one of the two X chromosomes has been inactivated during early embryonic life to achieve a compensation of X-linked gene products between males and females, leaving only one allele of X-linked genes functional. There are some X-linked genes escaping the X-inactivation, i.e., being expressed from both alleles. Escape from X-inactivation varies at different levels; some genes have both alleles active in some women but only one allele active in others, whereas some other genes have both alleles active in neoplastic tissue but only one allele active normally. The X-inactivation may be considered functionally equivalent to a loss of heterozygosity (LOH) for some genes, whereas escape from X-inactivation may be equivalent to functional gene amplification for others. The physiological LOH may make X-linked tumor suppressor genes lose their function more easily, compared with autosomal tumor suppressor genes, thus predisposing women to cancer formation more easily. Moreover, the human X chromosome contains many genes related to cancer or to sex and reproduction. All these properties of the X chromosome suggest that it may play more important roles than any autosomal chromosome in the development and progression of reproductive and urologic cancers.

Chromosomes, Human, X↗
PubMed2002

Maspin is up-regulated in premalignant prostate epithelia.

BACKGROUND: Maspin, a novel serine protease inhibitor, has been shown to inhibit prostate tumor cell motility and invasion in vitro and to inhibit prostate tumor growth and metastasis in vivo. Maspin expression in high-grade prostate carcinoma (PC) is reduced compared with that in low-grade PC. Interestingly, however, compared with low-grade PC, benign secretory prostate epithelial cells express significantly less maspin. This observation appears paradoxical to a putative tumor suppressive role of maspin in prostate carcinogenesis, and this finding issue needs to be clarified. METHODS: We examined maspin expression simultaneously in benign basal cells, benign secretory cells, high-grade prostate intraepithelial neoplasia (HGPIN), low-grade PC, and high-grade PC in 46 radical prostatectomy specimens plus 51 autopsy prostate glands by a combination of immunohistochemistry and in situ hybridization. RESULTS: Benign basal cells consistently expressed maspin at a high level. In PC, the loss of basolateral maspin expression coincides with loss of the basal cell layer. Maspin expression in secretory cells, on the other hand, appears to undergo a biphasic differential regulation, i.e., essentially absent in benign secretory cells, dramatically up-regulated in HGPIN, then progressively down-regulated through low-grade PC to high-grade PC. Maspin expression in PC is inversely correlated with tumor grade. Furthermore, maspin expression in HGPIN is inversely correlated with the Gleason's grade of the adjacent PC. CONCLUSIONS: An up-regulation of maspin expression precedes, rather than occurs at, the critical transition from premalignant prostate lesion of HGPIN to PC. Our data suggest maspin may mark an important transitional phase and play an important role in the premalignancy of the prostate gland.

Autopsy↗
PubMed1996

Prostate Cancer - Old Problems and New Approaches. (Part II. Diagnostic and Prognostic Markers, Pathology and Biological Aspects).

Diagnostic and prognostic markers for prostatic cancer (PCa) include conventional protein markers (e.g., PAP, PSA, PSMA, PIP, OA-519, Ki-67, PCNA, TF, collagenase, and TIMP 1), angiogenesis indicator (e.g., factor VIII), neuroendocrine differentiation status, adhesion molecules (E-cadherin, integrin), bone matrix degrading products (e.g., ICPT), as well as molecular markers (e.g., PSA, PSMA, p53, 12-LOX, and MSI). Currently, only PSA is used clinically for early diagnosis and monitoring of PCa. The histological differential diagnosis of prostatic adenocarcinoma includes normal tissues such as Cowper's gland, paraganglion tissue and seminal vesicle or ejaculatory duct as well as pathological conditions such as atypical adenomatous hyperplasia, atrophy, basal cell hyperplasia and sclerosing adenosis. A common PCa is characterized by a remarkable heterogeneity in terms of its differentiation, microscopic growth patterns and biological aggressiveness. Most PCa are multifocal with signi ficant variations in tumor grade between anatomically separated tumor foci. The Gleason grading system which recognizes five major grades defined by patterns of neoplastic growth has gained almost uniform acceptance. In predicting the biologic behavior of PCa clinical and pathological stages are used as the major prognostic indicators. Among the cell proliferation and death regulators androgens are critical survival factors for normal prostate epithelial cells as well as for the androgen-dependent human prostatic cancer cells. The androgen ablation has been shown to increase the apoptotic index in prostatic cancer patients and castration also promotes apoptotic death of human prostate carcinoma grown in mice. The progression of PCa, similarly to other malignancies, is a multistep process, accompanied by genetic and epigenetic changes, involving phenomenons as adhesion, invasion and angiogenesis (without prostate specific features).

Journal Article↗
PubMed1996

Prostate Cancer Old Problems and New Approaches. Part III. Prevention and Treatment.

In Part Three of this review, we begin with an analysis of prevention strategies for prostate cancer followed by a discussion of the clinical use of molecular techniques for the evaluation and treatment of patients with clinically localized prostate cancer. New developments in neutron and photon therapy of prostate cancer are addressed as well as the use of systemic radiotherapy for the treatment of bone metastases. Finally, we conclude with the role of hormonal therapy in the treatment of prostate cancer and the current status of development of chemo therapeutic regimens for the treatment of prostate cancer.

Journal Article↗
PubMedDate not supplied

Pathologic features the urologist should expect on a prostate biopsy.

In recent years, the pathological evaluation of prostate biopsy specimens has made great improvements in diagnostic accuracy and comprehensiveness. In this article, we review major pathological findings on prostate biopsy, their interpretation and reporting, as well as their clinical significance and utility. We discuss especially the clinically relevant histological features in either a positive or negative biopsy. We emphasize that both Gleason score and extent of cancer involvement in a needle core biopsy are important predictors of clinical outcome after either radical prostatectomy or radiation. Special issues regarding diagnosis and grading of minimal cancer on needle core biopsies are discussed. We also highlight the current standards on high-grade prostatic intraepithelial neoplasia and atypical small acinar proliferation on needle core biopsies. In summary, the pathology reports on needle biopsies are far beyond the simple presence or absence of cancer; they contain invaluable information to clinicians on patient management and counseling.

Biopsy, Needle↗