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Biomedical subjects

B Têtu

Publications and source records attributed to B Têtu.

At least 19 recordsLinked to original sources
PubMed2005

Lymph node metastases in low-grade endometrial stromal sarcoma.

OBJECTIVES: The objective of this study was to review our experience on lymphatic dissemination in patients with low-grade endometrial stromal sarcoma. METHODS: All cases diagnosed as low-grade endometrial stromal sarcoma or endolymphatic stromal myosis before October 2003 and who had lymph node sampling at some point in their evolution were retrieved from the files of the pathology and gynecologic oncology departments of l'Hotel-Dieu de Quebec University Hospital (HDQ). RESULTS: Fifteen patients with either limited lymph node biopsies or a complete lymph node dissection at some point in the course of their disease were found. Five of these patients (33%) presented lymph node metastases either at the initial hysterectomy, during a subsequent staging procedure, or at the time of a recurrence. CONCLUSION: These findings suggest that the incidence of lymph node involvement in low-grade endometrial stromal sarcoma is higher than expected. More extensive sampling of lymph nodes in a larger number of patients may allow a better understanding of the frequency and prognostic significance of these metastases.

Adult↗
PubMed2003

Leiomyosarcoma of urinary bladder following cyclophosphamide therapy: report of two cases.

Leiomyosarcoma of urinary bladder is rare, although it is the most common mesenchymal tumor in adults. We report two cases of this tumor following cyclophosphamide therapy. The first case is from a 53-year-old man with Wegener's granulomatosis treated for 6 years with cyclophosphamide. He presented with painless hematuria, and the initial biopsy of the bladder tumor revealed a malignant spindle cell neoplasm. A final diagnosis of leiomyosarcoma was made on radical cystoprostatectomy. The second example is from a 21-year-old man who had received cyclophosphamide in early infancy for a bilateral retinoblastoma. He also presented with painless hematuria, and a bladder tumor was resected transurethrally and diagnosed as leiomyosarcoma. He underwent partial cystectomy two months later. Cyclophosphamide, when used for a neoplastic or non-neoplastic condition, is associated with an increased risk of developing bladder cancer. The distribution of histologic subtypes differs from that seen in spontaneous bladder tumors. A review of the literature shows an increased proportion of squamous cell carcinomas and sarcomas, especially leiomyosarcomas in cyclophosphamide exposed patients. Acrolein, a cytotoxic metabolite of cyclophosphamide excreted in urine, is regarded as the most likely causative agent.

Adult↗
PubMed2001

Expression of cathepsin D, stromelysin-3, and urokinase by reactive stromal cells on breast carcinoma prognosis.

BACKGROUND: Current literature suggests that several proteases act in a cascade to mediate remodeling of the extracellular matrix and favor cancer progression. Others and the authors of this study recently identified cathepsin D, stromelysin-3, and urokinase plasminogen activator (uPA) expression by reactive stromal cells as significant factors of poor prognosis in breast carcinoma. The authors evaluated the joint effect of protease expression on cancer aggressiveness. METHODS: Protease expression was analyzed by immunohistochemistry (cathepsin D) and in situ hybridization (stromelysin-3 and uPA) on formalin fixed paraffin embedded specimens from 557 breast carcinomas without distant metastasis at diagnosis and with an average of 10 years of follow-up. RESULTS: Of the 557 breast carcinomas, 80 (14.3%) expressed all 3 proteases, and 134 (24%) expressed none of them. An adjusted Cox model revealed significantly worse distant metastasis free survival (DMFS) with expression of all three proteases (P < 0.0001). The DMFS of patients whose tumor lacked at least one of the three proteases was similar to that of patients without any protease expression, irrespective of the type or number of proteases missing. CONCLUSIONS: This study suggests that proteases expressed by reactive stromal cells are interdependent and that a breach in the protease pathway may impair breast carcinoma progression.

Breast Neoplasms↗
PubMed2001

Markers of neck failure in oral cavity and oropharyngeal carcinomas treated with radiotherapy.

BACKGROUND: Neck management after radiotherapy remains controversial. It is not clear which patients may benefit from postradiotherapy neck dissection. Biologic markers may be useful in this setting. METHOD: This study includes 81 patients with oral cavity and oropharyngeal carcinomas. The primary tumor had been treated with radical radiotherapy. Immunohistochemical staining to p53, ki-67, NEU, HSP-27, and GST has been performed. RESULTS: There were 50 T1-2 and 31 T3-4 patients, as well as 36 NO and 45 N1-3. A total of 25 nodal failures was observed. With expressed HSP2, 23% of patients had neck failure compared with 51% when HSP-27 was absent (p = .02). With NEU overexpression, nodal control decreased from 72% to 34% (p = .008). In a Cox model, NEU (p = .01) and HSP-27 (p = .05) were associated with neck failure. CONCLUSIONS: HSP-27 and NEU expression may play a role in predicting nodal failure. This should be confirmed in a larger, prospective study.

Biomarkers, Tumor↗
PubMed2001

Duration of neoadjuvant androgen deprivation therapy before radical prostatectomy and disease-free survival in men with prostate cancer.

There is little evidence that neoadjuvant androgen deprivation therapy (ADT) of 3 months' duration before radical prostatectomy (RP) favorably influences disease-free survival. However, recent data suggest that prolonged treatment may improve outcome. We conducted a prospective cohort study to determine whether ADT of either standard or prolonged duration before RP influences the risk of prostate-specific antigen (PSA) failure. We followed 756 men treated for prostate cancer by RP between 1991 and 1998 in Quebec City. Of these, 240 received combined neoadjuvant ADT for either </=92 days (129 men) or >/=93 days (111 men), and 516 were treated by RP alone. Multivariate Cox regression was used to estimate the hazard ratios (HR) of PSA failure (>0.3 ng/mL) associated with treatment regimen controlling for age, clinical stage, grade, and initial PSA level. The median duration of follow-up was 4 years. Compared with men treated by RP alone, those who received neoadjuvant ADT for >/=93 days had an HR of PSA failure of 0.60. The inverse association with the risk of PSA failure became statistically significant from the third year on, reached its greatest magnitude after 4 years, and was still present 8 years after RP. No association was observed for ADT of </=92 days. These results suggest that neoadjuvant ADT before RP has a real, delayed, and persistent effect on disease-free survival, if and only if ADT is prolonged beyond 3 months.

Androgen Antagonists↗
PubMed2001

Transitional cell carcinoma of the endometrium associated with a benign ovarian Brenner tumor: a case report.

Transitional cell carcinomas (TCCs) of the endometrium are rare, and only 10 cases have been described to date. We report the case of a 46-year-old woman who developed both a TCC of the endometrium and a benign ovarian Brenner tumor. Such an association has not yet been reported in the literature. Immunohistochemical studies of the uterine tumor showed cytokeratin 7 positivity and cytokeratin 20 negative staining, which was consistent with a Müllerian derivation. Human papilloma virus (HPV) immunostaining as well as polymerase chain reaction (PCR) analysis using primers for HPV types 6, 11, 16, and 18 failed to detect viral DNA. The coexistence of a TCC of the endometrium and an ovarian Brenner tumor might be coincidental but raises the possibility of a field effect, as seen with multifocal endometrioid tumors or multiple urinary tract TCCs.

Brenner Tumor↗
PubMed2001

Selective culture of epithelial cells from primary breast carcinomas using irradiated 3T3 cells as feeder layer.

The main drawback of the selective culture of human mammary epithelial cells from primary breast cancer is the overgrowth of tumor-associated stromal fibroblasts. This drawback may be overcome by using, in primary culture, lethally irradiated 3T3 cells which act as a feeder layer to maintain tumor-derived epithelial cell proliferation. These 3T3 cells, exposed to 60 Gy at confluence, form a specific cellular substrate which constitutes an obstacle to fibroblast attachment. Enzyme-disaggregated breast cells from six primary breast carcinomas were cocultured over lethally irradiated but living 3T3 cells. The method led to the purification of tumor-derived epithelial cells from all six cancer samples, and long-term culture was obtained in one. The epithelial nature of these purified tumor-derived epithelial cells was demonstrated by their general morphology and by the expression of cytokeratins and Epithelial Membrane Antigen. These results confirm the stimulatory effect of a this stromal feeder layer on breast epithelial cell growth and show that this stromal feeder layer can also control the fibroblast overgrowth. Our results provide an alternative approach in the selective culture of epithelial cells from primary breast carcinoma.

3T3 Cells↗
PubMed2001

Renal angiomyolipoma: further immunophenotypic characterization of an expanding morphologic spectrum.

BACKGROUND: Renal angiomyolipoma is a benign tumor histologically characterized by proliferation of spindle cells, epithelioid cells, and adipocytic cells in concert with many thick-walled blood vessels. To add further diagnostic confusion, an epithelioid cell-predominant variant of renal angiomyolipoma has recently been described. HMB-45 immunoreactivity correlates with ultrastructural striated organelles that closely resemble premelanosomes, although no evidence of melanogenesis has been documented in this tumor. OBJECTIVE: To further characterize the immunophenotypic and ultrastructural profile of renal angiomyolipoma based on phenotypic cell type (epithelioid, spindle, and adipocytic cell). DESIGN: Formalin-fixed, paraffin-embedded tissues from 27 renal angiomyolipomas and 8 renal cell carcinomas were immunostained with monoclonal antibodies to the melanoma-associated antigens HMB-45, HMB-50, NKI/C3 (CD63), and tyrosinase; the smooth muscle-related antigens calponin and muscle-specific actin (HHF-35); S100; and cytokeratin (CK). All renal angiomyolipomas were also immunostained with a polyclonal antibody to renin. Ultrastructural examination was performed on 9 selected cases. RESULTS: All renal angiomyolipomas stained positive for HMB-45, HMB-50, NKI/C3, muscle-specific actin (HHF-35), and calponin. Overall, HMB-45, HMB-50, and NKI/C3 preferentially stained the epithelioid cells. Tyrosinase staining was present in 50% of the renal angiomyolipomas with adequate tissue for staining (12 of 24 cases); positive staining and intensity paralleled HMB-45, HMB-50, and NKI/C3. Muscle-specific actin (HHF-35) and calponin preferentially stained the spindle cells. The adipocytic cells stained positive for both melanoma-associated antigens and smooth muscle antigens. Epithelioid cells, spindle cells, and adipocytic cells were CK, S100, and renin negative. Ultrastructural findings paralleled immunohistochemical staining patterns. Premelanosome-like organelles and electron dense granules were more readily detected in the epithelioid cells within the tumor, whereas ultrastructural characteristics of smooth muscle cells were more easily found in the spindle cells. All renal cell carcinomas stained positive for CK, NKI/C3 staining was variable, and all were negative for HMB-45, HMB-50, smooth muscle actin (HHF-35), and calponin. CONCLUSION: In renal angiomyolipoma, the epithelioid and spindle cells have preferential staining patterns for melanoma-associated antigens versus smooth muscle antigens, respectively. Positivity in renal angiomyolipoma for HMB-50, NKI/C3, and tyrosinase, in addition to HMB-45, provides evidence for the presence of different melanoma-associated gene products. Immunophenotypic overlap of the 3 histologically distinct renal angiomyolipoma cell populations suggests a common cell line, supporting a unitarian concept for renal angiomyolipoma. Ultrastructural characteristics of the 3 renal angiomyolipoma cell phenotypes parallel the immunophenotype, giving further support to a common cell line. Our study lends further credence to the perivascular epithelioid cell concept as proposed by Bonetti and colleagues.

Actins↗
PubMed2000

Establishment and characterization of a new cell line derived from a human primary breast carcinoma.

A new cell line, designated HDQ-P1, was successfully established from a primary ductal infiltrating mammary carcinoma by using a 3T3 feeder layer lethally irradiated to 60 Gy. The HDQ-P1 cells have been grown in culture for over 115 passages and have a doubling time of 60 hours. Characterization of the cell line was performed. This included morphology by light and transmission electron microscopy, karyotype, growth rate, telomerase expression, tumor antigen expression, xenograft implantation into nude mice, colony formation in soft agar, TP53 sequencing, and gene copy number of C-MYC, C-ERBB-2, and C-H-RAS oncogenes. The epithelial nature of this cell line was confirmed by ultrastructural analysis, expression of cytokeratins, and epithelial membrane antigen. The HDQ-P1 cells possess an extensively rearranged and polyploid karyotype, with an average of 20 recurrent marker chromosomes. Scatchard analysis demonstrated that both primary tumor and HDQ-P1 cells were estrogen- and progesterone-receptor negative. The HDQ-P1 cells had the same expression of human telomerase reverse transcriptase as other established breast cancer cell lines such as MDA-MB-231, SK-BR-3, and MCF-7. Direct DNA sequencing showed a point mutation which yielded to a stop codon at the amino acid 213 in exon 6 of the TP53 gene. A five-fold amplification of C-MYC was observed in HDQ-P1 cells. No amplification of C-ERBB-2 and C-H-RAS genes were observed. This cell line presents unique characteristics and may prove to be a good experimental model for investigating breast cancer biology.

Animals↗
PubMed2000

Overexpression of the 27 KDa heat shock protein is associated with thermoresistance and chemoresistance but not with radioresistance.

PURPOSE: The heat shock protein (hsp27) correlates with thermotolerance and chemoresistance. Our main objective was to assess the response to radiotherapy both in vitro and in vivo in correlation with various concentrations of hsp27. The second objective was to evaluate the relation between hsp27 and glutathione-s-transferase pi (GST pi). METHODS AND MATERIALS: For the in vitro study, thermoresistant cell lines, expressing various amounts of hsp27, were used to assess the role of this protein in radioresistance. To verify the efficiency of hsp27 in these cells lines to confer resistance to cytotoxic agents, these cells were also treated with heat shock and cisplatin. Furthermore, the role of hsp27 expression was studied in vivo by immunochemistry in 98 patients with head and neck squamous cell carcinoma treated by radiotherapy. hsp27 was correlated with local control of the tumor and with clinical and biologic factors potentially able to affect the local control, including p53, ki-67, ploidy, and GST. RESULTS: In vitro, high constitutive levels of expression of hsp27 did not significantly influence the survival curves of transfected cells exposed to radiation as compared to control cells although hsp27 overexpression was confirmed to increased the cellular resistance to heat and to cisplatinum. In vivo, we showed that overexpression of various amounts of hsp27 did not correlate with local control of the tumor. In vivo, hsp27 was only significantly associated with GST pi. Expression of GST pi was associated with poor local (p = 0.01) control and survival (p = 0.08) in a Cox model. CONCLUSIONS: It is concluded that the mechanisms responsible for hsp27-mediated heat and drug resistance are not involved in radioprotection.

Animals↗
PubMed2000

P53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers.

Sequencing of p53 exons 5-8 was carried out on 51 initial superficial bladder tumors selected on the basis of high grade and/or p53 overexpression (immunohistochemistry without antigen retrieval). Fourteen point mutations in 13 tumors and one 21 bp deletion in another tumor were identified. In addition, a germ-line mutation corresponding to a previously described polymorphism was detected in exon 6, in two tumors. Mostly G-->A transitions (10) were found. Only three occurred at CpG sites, suggesting a major role for exogenous carcinogens in bladder tumorigenesis. Immunostaining for p53 and MDM2, using antigen retrieval, was carried out on the same tumors. A correlation was found between the percentage of p53-positive cells and the presence of p53 mutations (P = 0.005). No correlation was found between overexpression of p53 and MDM2 in this selected cohort of mostly high grade tumors. The presence of p53 mutations was also analyzed as a function of the smoking habits of the patients. A significant association was found between the presence of p53 point mutations and the number of years of smoking (P = 0.043). All patients with tumors carrying missense or nonsense p53 mutations had smoked for >/=30 years and if former smokers, had stopped for </=5 years. However, no correlation was found between the presence of p53 point mutations and the number of cigarettes smoked. The deletion mutation was the only one present in a tumor from a non-smoker. The data suggest that duration of exposure to carcinogens is the most critical factor in p53 mutagenesis in bladder cancer.

Genes, p53↗
PubMed2000

Nuclear DNA content, an adjunct to p53 and Ki-67 as a marker of resistance to radiation therapy in oral cavity and pharyngeal squamous cell carcinoma.

Factors of prognosis and radioresistance in oral cavity and pharyngeal squamous cell carcinoma (OCPSCC) are limited. In the present study, the usefulness of tumor DNA content in predicting radioresistance in patients with OCPSCC has been investigated. Radioresistance has been defined as local recurrence or tumor persistence after radiation therapy. DNA-ploidy analysis was performed by static cytometry on smears of cell suspensions obtained from formalin-fixed paraffin-embedded material and stained with Feulgen. DNA-ploidy was correlated with the proliferation rate (Ki-67) and p53 protein accumulation obtained by immunohistochemistry. The follow-up of patients ranged from 8 to 62 months. Radioresistance was more common in non-diploid tumors; 14/28 (50%) non-diploid tumors recurred, whereas only 3 (10.7%) out of 28 diploid tumors had local failure (P=0.0019). Proliferation rate and p53 accumulation, evaluated by immunohistochemistry, also added prognostic information. Twelve out of 14 failures were from non-diploid tumors with a low proliferation rate (Ki-67<20%), whereas none of 20 p53-negative diploid tumors developed recurrences. This study showed that non-diploid tumors responded poorly to radiotherapy. DNA content appeared, therefore, as a significant prognostic marker for the evaluation of OCPSCC in patients receiving radiation therapy. This study also showed that DNA content adds information to p53 accumulation and the proliferation rate (Ki-67) for the purposes of determining patient management.

Adult↗
PubMed1999

Neoadjuvant hormonal therapy before radical prostatectomy and risk of prostate specific antigen failure.

PURPOSE: To date there is little information on the long-term effect of neoadjuvant hormonal therapy on prostate cancer progression. We performed a prospective study to determine whether patients with prostate cancer receiving neoadjuvant hormonal therapy before radical prostatectomy (hormonal therapy group) have a lower risk of prostate specific antigen (PSA) failure than those treated with radical prostatectomy alone (prostatectomy group). We also evaluated whether type of neoadjuvant hormonal therapy and duration were associated with the risk of PSA failure. MATERIALS AND METHODS: We followed 680 men initially treated for prostate cancer with radical prostatectomy between January 1988 and December 1997 at our university hospital. Of the patients 292 received neoadjuvant hormonal therapy. Median followup was 38 months. Cox regression analysis was used to assess the association between neoadjuvant hormonal therapy and PSA failure (greater than 0.3 ng./ml.) controlling for age, clinical stage, grade, initial PSA and adjuvant therapies. RESULTS: Surgical margins were positive less often in the hormonal therapy (25%) than the prostatectomy (47%) group (p = 0.0001). PSA failure was observed in 163 patients and the 5-year failure rate was 33%. No difference in risk of PSA failure was observed overall between the hormonal therapy and prostatectomy groups (hazards ratio 0.94, 95% confidence interval 0.68 to 1.30). Treatments with antiandrogen alone for any duration, and those combining antiandrogen and luteinizing hormone-releasing hormone analogue for 3 months or less were not associated with improved survival. However, patients receiving combined therapy for more than 3 months had a significantly lower risk of PSA failure than those treated with radical prostatectomy alone (hazards ratio 0.52, 95% confidence interval 0.29 to 0.93). CONCLUSIONS: Prolonged neoadjuvant hormonal therapy combining antiandrogen and luteinizing hormone-releasing hormone analogue may improve disease-free survival after radical prostatectomy.

Adult↗
PubMed1999

Prognostic value of the proliferative index determined by Ki-67 immunostaining in superficial bladder tumors.

The biological behavior of urothelial carcinomas remains unpredictable. The objective of this study was to determine the prognostic value of Ki-67 index in superficial papillary bladder tumors and to correlate it with the S-phase fraction (SPF) measured by flow cytometry. Three hundred nineteen patients with newly diagnosed superficial (pTa, pT1) bladder tumors were included between September 1990 and April 1992. Patients with bladder carcinoma in situ alone were excluded. We observed 255 pTa tumors and 64 pT1 tumors, whereas 111 lesions were classified as grade G1 and 208 as grade G2-G3. Ki-67 immunostaining was performed on paraffin-embedded material using a 3-step immunoperoxidase procedure with the murine monoclonal antibody MiB1. The relation between Ki-67 expression and prognostic variables (stage, grade, tumor size, multifocality, age, and sex) was investigated by the chi-square test. Cox regression was used to describe the association between Ki-67 and tumor recurrence in 308 patients with follow-up while adjusting for potentially confounding prognostic variables. The frequency of high Ki-67 expression (> or =10%) increased with stage (P = .005) and grade (P = .001), but not with tumor size or multifocality. Two hundred one patients experienced tumor recurrence in a median follow-up of 68 months. Stage, grade, tumor size, and multifocality were all independent predictors of recurrence. Ki-67 index greater than 10% was found to be an independent predictor of tumor recurrence among patients with tumors larger than 3 cm in diameter (HR = 2.05, CI = 1.18-3.55), but not those with smaller size tumors. With regards to the DNA index, a significant but weak correlation was observed between Ki-67 expression and the SPF (Spearman's correlation coefficient = 0.23, P = .004). In addition, aneuploid tumors had significantly higher expression of Ki-67 (22.5%) than diploid tumors (10.1%) (P = .0006). Moreover, patients with DNA aneuploid bladder tumors were more likely to have more than 10% Ki-67-positive cells than those with diploid tumors. In patients with newly diagnosed pTa or pT1 bladder tumors, a Ki-67 index above 10% is an independent predictor of shorter time to recurrence only in those with tumors larger than 3 cm.

Aged↗
PubMed1999

Prolonged neoadjuvant combined androgen blockade leads to a further reduction of prostatic tumor volume: three versus six months of endocrine therapy.

OBJECTIVES: In most clinical trials that have investigated the potential beneficial effects of neoadjuvant combined androgen blockade (CAB) in clinically localized prostate cancer, CAB has been given for 3 months, but no data are available on the influence of a longer duration of neoadjuvant CAB on the pathologic features of prostate cancer. METHODS: Prostatectomy specimens of 40 patients, randomized to 3 (n = 18) or 6 (n = 22) months of neoadjuvant CAB, were blindly evaluated with regard to tumor volume, pathologic stage, and surgical margins. The morphologically most vital tumor areas were investigated for nucleolar size and MIB-1 defined proliferative activity. RESULTS: The patients treated for 6 months had a median tumor volume 60% lower than the 3-month treatment group (P = 0.005). In the 6-month treatment group, no residual tumor could be found in 2 cases, but the proportion of prostatectomy specimens with seminal vesical invasion and positive surgical margins was not statistically different from that after 3 months. Compared with untreated controls, tumor proliferative activity assessed by MIB-1 immunoreactivity was significantly lower at 3 and 6 months of neoadjuvant CAB (P = 0.01). However, in 2 of 1 7 examined tumors that had been treated for 6 months, high MIB-1 scores suggested a development toward therapy-resistant cancer. CONCLUSIONS: Prolonged neoadjuvant CAB for 6 months leads to a further decrease in prostatic tumor volume compared with the findings after 3 months. In a few instances, residual tumor areas with substantial MIB-1 defined proliferative activity persist at 6 months, thus indicating that in at least some cases, despite the overall decrease in tumor size, cancer cells can continue the cell cycle under CAB.

Aged↗
PubMed1999

Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases.

This study was aimed at investigating the influence of cathepsin D (CD) expression by cancer cells and stromal cells on breast cancer prognosis. This is a study of 1348 node-positive (NPBC) and node-negative (NNBC) breast cancers diagnosed between 1980 and 1986 and with a minimum follow-up of 5.2 years. CD expression was assessed by immunohistochemistry on archival material using a polyclonal antibody. The expression by cancer and stromal cells was assessed separately and correlated with distant metastasis free (DMFS) and overall survival (OS). Cancer cells expressed CD (more than 10% cells expressing CD) in 38.9% of cases and reactive stromal cells in 43.6%. CD expression by reactive stromal cells, and not cancer cells, correlated with several factors of poor prognosis by cancer cells. A strong association was also found with expression of other proteases (stromelysin-3, gelatinase A, and urokinase Plasminogen Activator) by these same reactive stromal cells. CD expression by cancer cells did not predict DMFS or OS but, by univariate analysis, CD expression by reactive stromal cells was associated with earlier recurrence and shorter survival in NNBC (p = 0.0425) and NPBC patients submitted to adjuvant chemotherapy (p = 0.0234). However, CD expression by reactive stromal cells remained a significant predictor of recurrence by multivariate analyses only in a subgroup of NPBC submitted to adjuvant chemotherapy. Overall, those data support the concept that proteases produced by reactive stromal cells are under cancer cell stimulation and that CD by stromal cells, and not cancer cells, influences the prognosis, but only in a subgroup of patients with breast cancer.

Adenocarcinoma↗
PubMed1999

Prostatic intraepithelial neoplasia and endocrine manipulation.

Prostatic intraepithelial neoplasia (PIN) is the most common precursor lesion of prostatic adenocarcinoma. In 50- to 70-year-old participants of a randomized screening program for prostate cancer (Rotterdam section of the ERSPC) the frequency of high-grade PIN as an isolated finding in sextant prostatic needle biopsies was estimated to be about 1%. As yet, data in literature on the impact of androgen deprivation on PIN lesions are limited, showing discrepant outcomes. In part this may be the consequence of the application of different criteria for the identification of PIN under conditions of androgen deprivation. Foci of PIN could be distinguished in the majority of radical prostatectomy specimens of men treated for 3 or 6 months with combined endocrine therapy. Endocrine manipulation led to architectural changes (remodelling) in residual PIN which were more pronounced at 6 months of endocrine therapy. This is consistent with a prolonged effect of androgen deprivation on this precursor lesion. The presence of MIB-1 immunopositive nuclei in PIN lesions suggests that they still have the potential to expand after cessation of therapy.

Aged↗