RESUMEN
BACKGROUND: As dihydrotestosterone (DHT) is the most potent androgen in the prostate, inhibition of the 5alpha-reductase isoenzymes, which convert testosterone to DHT, could be an appropriate target for the treatment of prostate cancer. METHODS: Eighty-one men with clinically localized prostate cancer received daily dutasteride 3.5 or 0.5 mg, or no therapy for 4 months before radical prostatectomy. Histopathological assessments were conducted on prostatectomy specimens. RESULTS: Treatment with dutasteride was associated with reductions in serum and intraprostatic DHT of >or=90%, and a decrease in total prostate and tumor volumes. No effect of dutasteride was noted on Gleason grade. Histopathological effects on benign tissue were similar but less prominent than those seen with androgen ablation, whereas there was no significant difference in cancer histology among the groups. CONCLUSIONS: Dutasteride treatment results in similar but less marked changes compared with androgen ablation.
Asunto(s)
Inhibidores de 5-alfa-Reductasa , Adenocarcinoma/tratamiento farmacológico , Azaesteroides/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/sangre , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dihidrotestosterona/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Dutasterida , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Próstata/efectos de los fármacos , Próstata/metabolismo , Próstata/patología , Prostatectomía , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Resultado del TratamientoRESUMEN
An unusual variant of prostatic intraepithelial neoplasia with prominent and extensive squamous differentiation is described. The lesion was identified in the transition zone of a 79 year old man with a three year history of increasing urinary obstructive symptoms and a clinical diagnosis of benign prostatic hyperplasia who underwent simple prostatectomy. Two years after surgery, prostatic biopsies showed atrophy and mild chronic inflammation, with no evidence of malignancy. This unusual intraepithelial lesion seems not to have been described before and may represent a new variant of high grade prostatic intraepithelial neoplasia (HGPIN) with squamous differentiation.
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Neoplasia Intraepitelial Prostática/patología , Neoplasias de la Próstata/patología , Anciano , Carcinoma Adenoescamoso/patología , Humanos , Inmunohistoquímica/métodos , Hibridación in Situ , Cariotipificación , Masculino , Prostatectomía , Hiperplasia Prostática/patología , Hiperplasia Prostática/cirugía , Neoplasia Intraepitelial Prostática/cirugía , Neoplasias de la Próstata/cirugíaRESUMEN
Prostatic basal cell proliferations range from ordinary basal cell hyperplasia (BCH) to florid basal cell hyperplasia to basal cell carcinoma. The distinction between these forms of BCH, including the variant with prominent nucleoli (formerly called atypical BCH), and basal cell carcinoma depends on morphological and immunohistochemical criteria and, in particular, on the degree of cell proliferation. In florid BCH, the proliferation index is intermediate between ordinary BCH and basal cell carcinoma. Immunohistochemistry is also useful for identifying the cell composition of the basal cell proliferations, including the basal cell nature of the cells, their myoepithelial differentiation, and c-erbB-2 oncoprotein expression. Based on the information derived from the literature and on the appearance and follow up of the case presented here, florid BCH might represent a lesion with an intermediate position between ordinary BCH and basal cell carcinoma. However, criteria useful for the identification of those cases with a true precursor nature are not available. In general, basal cell carcinoma is seen as a low grade carcinoma. The immunohistochemical expression of the c-erbB-2 oncoprotein, similar to that seen in breast cancer, might have therapeutic importance.
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Carcinoma Basocelular/diagnóstico , Hiperplasia Prostática/diagnóstico , Neoplasias de la Próstata/diagnóstico , Receptor ErbB-2/metabolismo , Anciano , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patología , Proliferación Celular , Diagnóstico Diferencial , Humanos , Técnicas para Inmunoenzimas , Masculino , Prostatectomía , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patologíaRESUMEN
The classification and grading of the non-invasive, intraepithelial neoplasms of the urothelium are based on the morphological pattern of growth-that is, papillary or flat (and endophytic)-and on their degree of architectural and cytological abnormalities. Recent advances in the morphological, molecular, and quantitative evaluation of these lesions have contributed to the refinement of the current classification and grading schemes. However, some controversies on the precise criteria and terminology, especially when the papillary lesions are concerned, are still present.
Asunto(s)
Carcinoma in Situ/patología , Carcinoma de Células Transicionales/patología , Neoplasias de la Vejiga Urinaria/patología , Carcinoma in Situ/clasificación , Carcinoma in Situ/genética , Carcinoma de Células Transicionales/clasificación , Carcinoma de Células Transicionales/genética , Cromosomas Humanos Par 9 , Humanos , Pérdida de Heterocigocidad , Terminología como Asunto , Neoplasias de la Vejiga Urinaria/clasificación , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
Renal angiomyolipoma is a benign neoplasm composed of variable proportions of blood vessels, smooth muscle, and adipose tissue. Smooth muscle, adipose tissue, blood vessels, and adjacent normal kidney tissue were separately microdissected from sections prepared from formalin-fixed, paraffin-processed tissues from angiomyolipomas from 18 women. X chromosome inactivation analysis using the methylation pattern at exon 1 of the human androgen receptor gene on chromosome Xq11-12 was used to study the clonal origin of each component. Nonrandom inactivation of X chromosomes was found in six of the 15 informative tumors. The smooth muscle and adipose tissue showed differing patterns of nonrandom inactivation of X chromosomes in five angiomyolipomas and the same pattern of nonrandom inactivation of X chromosomes in one. Samples from the blood vessels showed random inactivation of X chromosomes in all informative cases. Our data showed that the adipose tissue and smooth muscle cells of renal angiomyolipoma are both monoclonal but may arise independently. The coexistence of tumor subclones with morphologic heterogeneity can lead to the formation of a clinically detectable tumor.
Asunto(s)
Angiomiolipoma/genética , Neoplasias Renales/genética , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Angiomiolipoma/metabolismo , Angiomiolipoma/patología , Vasos Sanguíneos/citología , Vasos Sanguíneos/metabolismo , Células Clonales , Clonación Molecular , Cartilla de ADN/química , ADN de Neoplasias/análisis , Disección , Femenino , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Micromanipulación , Persona de Mediana Edad , Músculo Liso/citología , Músculo Liso/metabolismo , Reacción en Cadena de la Polimerasa , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Aberraciones Cromosómicas Sexuales , Cromosoma XRESUMEN
BACKGROUND: Needle ablative therapy has recently generated a lot of interest in the urologic community. We compare renal lesions produced in a porcine model using three forms of needle ablative energy: cryoablation (CR), dry radiofrequency (RF), and saline augmented radiofrequency (SARF). STUDY DESIGN: In 10 farm pigs, under ultrasonographic guidance, 40 laparoscopic renal lesions were produced: 825-mm CR lesions were produced with 2.4-mm cryoprobes (Endocare Inc, Irvine, CA), after 1-mL preinfusions of 14.6% saline, 12 SARF lesions were created with 22-gauge needles (2 mL/minute 14.6% saline, 50 W 510 kHz RF for 60 seconds), 12 RF lesions were created with a 2-cm array LeVeen electrode and an RF2000 generator using impedance limited 30 to 60 W double activations (Radiotherapeutics Corp, Mountain View, CA), and 8 RF lesions were produced using 22-gauge needles and double 10 W activations with the RF2000 generator. Eight animals were sacrificed after 1 week for acute pathology. An additional two animals were sacrificed at 8 weeks to provide chronic pathology results for the LeVeen dry RF and SARF modalities. RESULTS: CR produced a regular 18- to 22-mm zone of complete necrosis bordered by a 1.5- to 2.5-mm zone of partial necrosis. Acutely, LeVeen RF and single-needle RF produced lesions 25 to 45 mm and 6 to 10 mm wide, respectively. Acutely, SARF produced irregular cone-shaped lesions 15 to 31 mm wide. Only one of eight acute LeVeen RF lesions showed complete necrosis; none of the four 8-week LeVeen RF lesions displayed complete necrosis. Two of the four 8-week SARF lesions displayed complete necrosis. The remainder of the LeVeen RF, single-needle RF, and SARF lesions showed early, indeterminate tubular damage with relative glomerular sparing and bands of complete necrosis (0.5 to 1.5 mm) and inflammation (0.5 to 2 mm) at the periphery. Only CR could be consistently monitored with laparoscopic ultrasonography. CONCLUSIONS: Renal cryoablation produces well-defined, completely necrotic lesions that can be monitored reliably with ultrasonography. Longer followup may be required to characterize the full extent of renal necrosis produced by RF, but in the short run, none of the RF modalities reliably produced 100% necrosis in all cases.
Asunto(s)
Criocirugía/instrumentación , Hipertermia Inducida/instrumentación , Riñón/patología , Animales , Femenino , Glomérulos Renales/patología , Laparoscopía , Necrosis , Cloruro de Sodio , PorcinosRESUMEN
We assessed diagnostic criteria among 38 spindle cell tumors of the urinary bladder and obtained follow-up in 36 patients. Patients comprised 28 males and 10 females aged 2.5 months to 87 years. Hematuria was the commonest presenting symptom (27 patients). After review and immunohistochemical workup, 17 patients had inflammatory pseudotumor (myofibroblastic tumor), 4 postoperative spindle cell nodule, 1 leiomyoma, 13 sarcoma (7 low-grade; 6 high-grade), and 3 carcinoma. Mean age was 38 years for pseudotumor (range 15 to 74), 65 for postoperative spindle cell nodule, 51 for sarcoma, and 76 for carcinoma. Size of pseudotumor averaged 4.4 +/- 0.7 cm (range 1.5 to 13.0), similar to sarcoma, 4.0 +/- 0.6 cm (range 0.5 to 7.0). Similar proportions of benign tumors and sarcomas had muscularis propria invasion. The criteria that best differentiated sarcoma from inflammatory pseudotumor were presence of necrosis at the tumor-detrusor muscle interface in muscle-invasive cases, and nuclear atypia. Sarcoma also had less prominent microvasculature, less variable cellularity, consistently > or =1 mitotic figure per 10 high-power fields, and predominant acute inflammation without plasma cells. p53 protein nuclear immunostaining was moderate, unlike the rare to absent staining in pseudotumors. Because all 12 sarcomas were desmin-negative, we did not call them leiomyosarcoma; they overlapped with benign tumor in epithelial, mesenchymal, and actin immunostaining. Among 12 sarcoma patients, 2 died of tumor (at 3 months). Two of four experienced tumor recurrence after partial cystectomy (2 and 26 months). No pseudotumors recurred after transurethral resection or partial cystectomy, although one patient, 5 months after transurethral resection, had histologically identical pseudotumor that the surgeon considered residual. Another patient with pseudotumor, not a candidate for tumor ablation after transurethral resection, had continued tumor growth and he died of urosepsis. In conclusion, inflammatory pseudotumor, although overlapping with sarcoma in presentation, age range, and size, does not metastasize and remains histologically distinct from low-grade sarcoma.
Asunto(s)
Granuloma de Células Plasmáticas/patología , Sarcoma/patología , Enfermedades de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patología , Actinas/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Cistectomía , Desmina/análisis , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Granuloma de Células Plasmáticas/metabolismo , Granuloma de Células Plasmáticas/cirugía , Humanos , Inmunohistoquímica , Lactante , Queratinas/análisis , Masculino , Persona de Mediana Edad , Mucina-1/análisis , Músculo Liso/química , Proteínas S100/análisis , Sarcoma/metabolismo , Sarcoma/cirugía , Resultado del Tratamiento , Proteína p53 Supresora de Tumor/análisis , Vejiga Urinaria/química , Vejiga Urinaria/patología , Vejiga Urinaria/ultraestructura , Enfermedades de la Vejiga Urinaria/metabolismo , Enfermedades de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/cirugía , Vimentina/análisisRESUMEN
PURPOSE: We evaluated differences in clinical and pathological outcomes between Gleason 3 + 4 and 4 + 3 prostate cancer. MATERIALS AND METHODS: The radical prostatectomy whole mounted specimens from 263 men with pathological Gleason 7 tumors were identified. Gleason 3 + 4 and 4 + 3 tumors were compared in regard to pathological variables and outcome. Significance of clinical and pathological data on progression-free survival was analyzed. RESULTS: Of the tumors 34% had a primary Gleason grade of 4, and were more likely than those with primary grade 3 to have seminal vesicle involvement (34% versus 18%, p = 0.006), a higher pathological stage (pT3 55% versus 42%, N+ 13% versus 3%, 0.001), extraprostatic extension (58% versus 38%, 0.001) and higher median preoperative prostate specific antigen (PSA) (13.5 versus 9.0 ng./ml., respectively <0.001). Mean followup plus or minus standard deviation was 6.8 +/- 1.9 years. The overall 10-year crude, cancer specific and progression-free survival rates were 83%, 99% and 58%, respectively. Primary Gleason grade was significantly associated with progression-free (risk ratio 1.6, 95% confidence interval 1.08 to 2.5, p = 0.02) but not crude and cancer-specific survival. Univariately, primary Gleason grade 4 was associated with progression-free survival, as were percent Gleason 4, seminal vesicle invasion, lymph node involvement, pT stage, margin status, DNA ploidy, preoperative PSA, cancer volume and extent of extraprostatic extension. Multivariately, only preoperative PSA (p <0.001), seminal vesicle invasion (<0.001) and DNA ploidy (0.002) were associated with progression-free survival. Primary Gleason grade and percent Gleason 4 were not identified as independently associated with progression-free survival. CONCLUSIONS: In patients with Gleason 7 score prostate cancer primary Gleason grade 3 and 4 cancers are different in pathological parameters and prognosis. However, primary Gleason grade does not provide any additional information than other known prognostic factors, such as preoperative PSA, seminal vesicle invasion and DNA ploidy.
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Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Adenocarcinoma/sangre , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Vesículas Seminales/patología , Análisis de SupervivenciaRESUMEN
BACKGROUND: The goal of this study was a karyometric characterization of secretory cell nuclei in high-grade prostatic intraepithelial neoplasia (PIN) lesions. Specifically, the hypothesis is tested that distinctly different subgroups of nuclei exist in these lesions. METHODS: High-resolution images of 1,713 nuclei from high-grade PIN lesions were recorded. Karyometric features were computed. Discriminant function scores against normal reference nuclei, and nuclear abnormality values were derived. Data sets were processed by a nonsupervised learning algorithm to establish the presence of subgroups of nuclei with statistically different nuclear chromatin distributions. RESULTS: Three sets of nuclei were formed, facing an intact basal cell layer, a near vanishing basal cell layer, and a gap in the basal cell layer. For each set, a nonsupervised learning algorithm formed three statistically different subgroups of approximately equal sizes. Each subgroup is found in every one of the three sampling locations. The total optical density distribution of nuclei in two subgroups suggests an aneuploid distribution, the third subgroup has a near diploid distribution. CONCLUSIONS: Secretory cell nuclei in high-grade PIN lesions are a heterogeneous population, forming statistically different subgroups. Studies aimed at characterizing the progression of such lesions should consider the inhomogeneous nature of these nuclei.
Asunto(s)
Núcleo Celular/ultraestructura , Cromatina/ultraestructura , Neoplasia Intraepitelial Prostática/patología , Algoritmos , Simulación por Computador , Progresión de la Enfermedad , Humanos , Cariometría , Masculino , Neoplasia Intraepitelial Prostática/genética , Neoplasia Intraepitelial Prostática/ultraestructura , Valores de ReferenciaRESUMEN
CONTEXT: Molecular analysis of microsatellite alterations of biologically distinct tumor cell subpopulations from the same patient may aid in the determination of tumor origin and further our understanding of the genetic basis of cancer progression. DESIGN: The authors examined the pattern of allelic loss with polymorphic microsatellite markers on chromosome 9p21 (D9S161, D9S171, IFNA), regions of putative tumor suppressor gene p16, and on chromosome 17p13 (TP53), the p53 locus, in matched primary and metastatic bladder cancers from 9 patients. All patients underwent cystectomy for bladder cancer and had regional lymph node metastases at the time of surgery. Genomic DNA was prepared from primary cancers and matched synchronous lymph node metastases using a microdissection method. RESULTS: The overall frequency of allelic loss was 78% in primary cancer and 89% in paired metastatic cancer. The frequency of allelic loss in the primary cancer was 86% with D9S161, 67% with D9S171, 71% with IFNA, and 80% with TP53. The frequency of allelic loss in matched metastatic cancer was 100% with D9S161, 62% with D9S171, 71% with IFNA, and 80% with TP53. An identical pattern of allelic imbalance (allelic loss or retention) at multiple DNA loci was observed in matched primary and metastatic carcinoma in 8 (88%) cases. One case showed allelic loss in the metastasis, but not in the primary cancer. CONCLUSIONS: The pattern of allelic loss at chromosome 9p21 (p16) and 17p13 (p53) was generally maintained during cancer progression to metastasis, and identical allelic loss in primary cancer was conserved in paired metastatic carcinoma. These data suggest that these genetic changes may be useful in establishing a diagnosis and determining tumor origins in difficult cases.
Asunto(s)
Cromosomas Humanos Par 17 , Cromosomas Humanos Par 9 , Pérdida de Heterocigocidad , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Anciano , Anciano de 80 o más Años , Mapeo Cromosómico , Progresión de la Enfermedad , Femenino , Genes p53 , Marcadores Genéticos , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Masculino , Repeticiones de Microsatélite , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Polimorfismo Genético , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
There is a marked decrease in the prevalence and extent of high-grade prostatic intraepithelial neoplasia (PIN) in men with prostate cancer after androgen deprivation therapy (ADT) when compared with untreated cases. Basal cell hyperplasia, cytoplasmic clearing, and prominent atrophy of benign acini, with decreased ratio of acini to stroma, accompany this decrease. These findings indicate that the benign and dysplastic prostatic epithelium is androgen dependent. In the normal prostatic epithelium, luminal secretory cells are more sensitive to the absence of androgen than basal cells, and the proliferative cells of high-grade PIN share this androgen sensitivity. The loss of some normal, hyperplastic, and dysplastic epithelial cells with ADT is probably because of acceleration of programmed single-cell death. Remarkably little is known about the comparative effect of different forms of chemical ADT on PIN and cancer, although there appears to be a limited and consistent repertoire of morphologic responses to all forms of this therapy. Conversely, blockade of 5alpha-reductase with finasteride has little or no effect on PIN (or benign epithelium and cancer), unlike other forms of ADT. A recent international consensus conference sponsored by the World Health Organization concluded that identification of high-grade PIN offered the possibility of chemoprevention with hormonal therapy to block the development of clinical cancer. Multiple chemoprevention trials are planned or under way to address this hypothesis.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Neoplasia Intraepitelial Prostática/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/prevención & control , Antagonistas de Andrógenos/administración & dosificación , Antineoplásicos Hormonales/administración & dosificación , Quimioprevención/métodos , Quimioprevención/tendencias , Esquema de Medicación , Humanos , Masculino , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/patología , Próstata/patología , Neoplasia Intraepitelial Prostática/patologíaRESUMEN
BACKGROUND: Neuroendocrine (NE) differentiation may be related to the growth and progression of prostate cancer, especially androgen-insensitive tumors. Recently the over-expression of a new anti-apoptosis protein, survivin, has attracted attention for its potential implication in many human cancers. The fact that NE cells in prostate are bcl-2 negative prompted us to investigate if the prostatic NE cells over-express survivin. METHODS: Double immunohistochemical staining and immunofluorescence of chromogranin A (CgA) and survivin were performed in 57 patients with localized prostate cancer who underwent radical prostatectomy. The terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method was used for apoptosis detection in three prostate cancer specimens with NE differentiation. The relationship between NE differentiation and clinicopathological characteristics, disease progression as well as patient survival, were analyzed retrospectively. RESULTS: It was found that NE cells in both benign and malignant prostate tissues over-expressed the anti-apoptosis protein survivin. While apoptosis was detected in non-NE epithelial cells, all NE cells were negative for apoptosis detection. During the period of follow-up, 17 (63%) of 27 patients with NE differentiation had prostate cancer progression, while 12 (40%) of 30 patients without NE differentiation had systemic prostate cancer progression. 10 (37%) of 27 patients with NE differentiation died from prostate cancer during the period of follow up, while 6 (20%) of 30 patients without NE differentiation died from prostate cancer. However, none of these characteristics reached statistical significance, probably because of the small number of cases enrolled. CONCLUSIONS: This study discovers that all the prostatic NE cells express the new anti-apoptosis protein survivin. This provides a strong molecular basis for the hypothesis that NE cells may endure stressful conditions and escape from apoptosis. While our results suggest a trend of NE differentiation with poorer prognosis, the prognosis implication cannot be concluded due to our small sample size.
Asunto(s)
Proteínas Asociadas a Microtúbulos , Sistemas Neurosecretores/citología , Sistemas Neurosecretores/patología , Próstata/citología , Próstata/patología , Neoplasias de la Próstata/patología , Proteínas/análisis , Anciano , Apoptosis/fisiología , Biomarcadores de Tumor , Distribución de Chi-Cuadrado , Cromogranina A , Cromograninas/inmunología , Progresión de la Enfermedad , Humanos , Inmunoglobulina G/inmunología , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Proteínas Inhibidoras de la Apoptosis , Masculino , Persona de Mediana Edad , Morfogénesis , Proteínas de Neoplasias , Pronóstico , Prostatectomía , Neoplasias de la Próstata/inmunología , Células Madre/citología , SurvivinRESUMEN
BACKGROUND: -Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits. OBJECTIVE: -To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis. DESIGN: -We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases. RESULTS: -In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases. CONCLUSIONS: -CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.
Asunto(s)
Carcinoma/metabolismo , Proteínas de Filamentos Intermediarios/metabolismo , Queratinas/metabolismo , Ganglios Linfáticos/metabolismo , Metástasis Linfática , Neoplasias de la Vejiga Urinaria/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica/métodos , Queratina-20 , Queratina-7 , Masculino , Persona de Mediana Edad , Coloración y Etiquetado , Distribución TisularRESUMEN
BACKGROUND: There is a great need for accurate treatment and outcome prediction in cancer. Two methods for prediction, artificial neural networks and Kaplan--Meier plots, have not, to the authors' knowledge, been compared previously. METHODS: This review compares the advantages and disadvantages of the use of artificial neural networks and Kaplan--Meier curves for treatment and outcome prediction in cancer. RESULTS: Artificial neural networks are useful for prediction of outcome for individual patients with cancer because they are as accurate as the best traditional statistical methods, are able to capture complex phenomena without a priori knowledge, and can be reduced to a simpler model if the phenomena are not complex. Kaplan--Meier plots are of limited accuracy for prediction because they require partitioning of variables, require cutting continuous variables into discrete pieces, and can only handle one or two variables effectively. CONCLUSIONS: Artificial neural networks are an efficient statistical method for outcome prediction in cancer that utilizes all available powerful prognostic factors and maximizes predictive accuracy. Use of Kaplan--Meier plots for predictions is discouraged because of serious technical limitations and low accuracy.
Asunto(s)
Tablas de Vida , Modelos Estadísticos , Neoplasias/terapia , Redes Neurales de la Computación , Predicción , Humanos , Neoplasias/patología , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Epidemiologic studies suggest that populations that consume large amounts of dietary fat are at greater risk for prostate carcinoma. Arachidonic acid and its precursor, linoleic acid, are major ingredients of animal fats and many vegetable oils that are used in the regions where prostate carcinoma is prevalent. The metabolism of arachidonic acid by either the cyclooxygenase pathway or the lipoxygenase pathway generates eicosanoids, which have been implicated in the pathogenesis of a variety of human diseases, including cancer, and are now believed to play important roles in tumor promotion, progression, and metastasis. Studying these pathways in specimens from patients with prostate carcinoma, the authors recently demonstrated the overexpression of cyclooxygenase-2 in prostate adenocarcinoma. In the current study, the authors report the overexpression of lipoxygenase-5 (5-LO) in samples from patients with prostate adenocarcinoma. METHODS: Employing 22 pair-matched benign and malignant tissue samples that were obtained from the same patients with prostate carcinoma, the expression of 5-LO was determined using reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry and by measuring the levels of 5-hydroxyeicosatetraenoic acid (5-HETE) by radioimmunoassay. RESULTS: The mean level of 5-LO mRNA was six-fold greater (P < 0.001) in malignant tissue compared with benign tissue. The immunoblot analysis demonstrated that, compared with benign tissue, 5-LO protein was overexpressed in 16 of 22 samples examined and was 2.6 fold greater (P < 0.001) in malignant tissue. Immunohistochemical studies further verified 5-LO up-regulation in malignant tissue that was not present in benign tissue. The levels of 5-HETE, which is a metabolic product of arachidonic acid, was found to be 2.2-fold greater (P < 0.001) in malignant tumor tissue compared with benign tissue. CONCLUSIONS: To the authors' knowledge, this is the first in vivo study showing overexpression of 5-LO in patients with prostate carcinoma. This study suggests that inhibitors of arachidonic acid pathway in general and selective 5-LO inhibitors in particular may be useful for prevention or therapy in patients with prostate carcinoma.
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Adenocarcinoma/enzimología , Araquidonato 5-Lipooxigenasa/metabolismo , Neoplasias de la Próstata/enzimología , Adenocarcinoma/metabolismo , Anciano , Humanos , Ácidos Hidroxieicosatetraenoicos/metabolismo , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/metabolismo , ARN Mensajero/análisis , Radioinmunoensayo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Gleason grading is now the most widely used grading system for prostatic carcinoma in the United States. However, there are only a few studies of the interobserver reproducibility of this system, and no extensive study of interobserver reproducibility among a large number of experienced urologic pathologists exists. Forty-six needle biopsies containing prostatic carcinoma were assigned Gleason scores by 10 urologic pathologists. The overall weighted kappa coefficient kappa(w) for Gleason score for each of the urologic pathologists compared with each of the remaining urologic pathologists ranged from 0.56 to 0.70, all but one being at least 0.60 (substantial agreement). The overall kappa coefficient kappa for each pathologist compared with the others for Gleason score groups 2-4, 5-6, 7, and 8-10 ranged from 0.47 to 0.64 (moderate-substantial agreement), only one less than 0.50. At least 70% of the urologic pathologists agreed on the Gleason grade group (2-4, 5-6, 7, 8-10) in 38 ("consensus" cases) of the 46 cases. The 8 "nonconsensus" cases included low-grade tumors, tumors with small cribriform proliferations, and tumors whose histology was on the border between Gleason patterns. Interobserver reproducibility of Gleason grading among urologic pathologists is in an acceptable range.
Asunto(s)
Variaciones Dependientes del Observador , Neoplasias de la Próstata/patología , Humanos , Masculino , Estadificación de Neoplasias/métodos , Estadificación de Neoplasias/normas , Patología Clínica , Próstata/patología , Reproducibilidad de los Resultados , UrologíaRESUMEN
BACKGROUND: The presence of lymph node metastasis is a poor prognostic sign for patients with prostate carcinoma. Results of published reports on survival among patients with lymph node metastasis are difficult to assess because of treatment selections. The extent to which lymph node status will have an impact on a patient's survival is uncertain. METHODS: The authors analyzed 3463 consecutive Mayo Clinic patients who underwent radical prostatectomy and bilateral pelvic lymphadenectomy for prostate carcinoma between 1987 and 1993. Of these patients, 322 had lymph node metastasis at the time of surgery, and 297 lymph node positive patients also received adjuvant hormonal therapy within 90 days of surgery. The progression free rate and the cancer specific survival rate were used as outcome endpoints in univariate and multivariate Cox proportional hazards models. The median follow-up was 6.3 years. Progression was defined by elevation of serum prostate specific antigen (PSA) > or = 0.4 ng/mL after surgery, development of local recurrence, or distant metastasis documented by biopsy or radiographic examination. RESULTS: The 5-year and 10-year progression free survival rates (+/- standard error [SE]) for patients with lymph node metastasis were 74% +/- 2% and 64% +/- 3%, respectively, compared with 77% +/- 1% and 59% +/- 2%, respectively, for patients without lymph node metastasis. The 5-year and 10-year cancer specific survival rates were 94% +/- 1% and 83% +/- 4%, respectively, compared with 99% +/- 0.1% and 97% +/- 0.5%, respectively, for patients without lymph node metastasis. Among patients with a single lymph node metastasis, the 5-year and 10-year cancer specific survival rates were 99% +/- 1% and 94% +/- 3%, respectively. After adjustment for extraprostatic extension, seminal vesicle invasion, Gleason grade, surgical margins, DNA ploidy, preoperative serum PSA concentration, and adjuvant therapy, the hazard ratio for death from prostate carcinoma among patients with a single lymph node metastasis compared with patients who were without lymph node metastasis was 1.5 (95% confidence interval, 0.5-5.0; P = 0.478), whereas the hazard ratio for death from prostate carcinoma was 6.1 (95% confidence interval, 1.9-19.6; P = 0.002) for those with two positive lymph nodes and 4.3 (95% confidence interval, 1.4-13.0; P = 0.009) for those with three or more positive lymph nodes. There was no significant difference in the progression free survival rate among patients with or without lymph node metastasis in multivariate analysis after controlling for all relevant variables, including treatments (hazard ratio,1.0; 95% CI, 0.7-1.3; P = 0.90). CONCLUSIONS: Patients with prostate carcinoma who have multiple regional lymph node metastases had increased risk of death from disease, whereas patients with single lymph node involvement appeared to have a more favorable prognosis after radical prostatectomy and immediate adjuvant hormonal therapy. Excellent local disease control was achieved by using combined surgery and adjuvant hormonal therapy in patients with positive lymph nodes.
Asunto(s)
Carcinoma/mortalidad , Carcinoma/patología , Metástasis Linfática/patología , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Hormonales/uso terapéutico , Carcinoma/terapia , Causas de Muerte , Quimioterapia Adyuvante , Progresión de la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Pronóstico , Prostatectomía , Neoplasias de la Próstata/terapia , Estudios Retrospectivos , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
OBJECTIVES: The delivery of thermotherapy, cryotherapy, and interstitial radiation with minimal morbidity is dependent on the preservation of the prostatic urethra. Our aim was to determine the distribution of the distance between the urethra and the nearest prostate cancer. METHODS: We determined the location of cancer in 350 prostate cancers treated by radical prostatectomy between 1991 and 1993. Each pathologic specimen was totally embedded, serially sectioned, and whole mounted. For each prostate, the radial distance from the urethra to the nearest cancer was determined (urethral-cancer distance). The urethra-cancer distance was correlated with the clinical, pathologic, and laboratory factors. Univariate and multivariate associations with progression-free survival were determined. RESULTS: The mean follow-up was 6.1 years. Ninety-three patients had biochemical, local, or systemic cancer recurrence. The mean +/- SD distance from the urethra to the nearest cancer was 3 +/- 3 mm (range 0 to 18). In 58 patients (17%), the cancer touched the urethra. A decreasing urethra-cancer distance was associated with increasing rates of cancer recurrence (P = 0.009). The urethra-cancer distance correlated with each of the following preoperative factors: preoperative prostate-specific antigen (r = -0. 22, P <0.001), Gleason score in biopsy specimen (r = -0.13, P = 0.02), and percentage of Gleason score 4 or 5 in the biopsy specimen (r = -0.17, P = 0.008). CONCLUSIONS: The distance between the urethra and the nearest cancer was associated with prostate cancer outcome. Many patients have cancer close to the urethra. This finding may have implications for nonsurgical ablative therapies for prostate cancer.
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Recurrencia Local de Neoplasia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Uretra/patología , Anciano , Biopsia , Supervivencia sin Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prostatectomía , Resultado del TratamientoRESUMEN
Androgen deprivation induces substantial changes in the phenotype of prostate cancer that are accompanied by alterations in protein expression. Immunohistochemical studies allow precise cellular localization of such expression, thereby providing an understanding of the biochemical alterations caused by therapy. Expression of proteins may be increased (e.g., multiple growth factors, heat shock protein), decreased (e.g., microvessel density, proliferation markers, certain integrins), or remain unchanged (e.g., prostate specific antigen, prostatic acid phosphatase, prostate-specific membrane antigen, and other secretory proteins). Variations in immunoreactivity may be of prognostic value in some patients. This report summarizes the existing literature regarding changes in tissue expression of proteins, as determined by immunohistochemistry, and the clinical implications of these changes.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Biomarcadores de Tumor/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Andrógenos/metabolismo , Humanos , Inmunohistoquímica , Masculino , Pronóstico , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: Pet dogs and men share a vulnerability for the development of prostate carcinoma. The purpose of this study was to further characterize the clinical and pathologic features of spontaneous canine prostate carcinoma. METHODS: A multiinstitutional, retrospective study was conducted using 76 dogs with prostate carcinoma that underwent postmortem evaluation. For each case, clinical and pathologic data were tabulated and hematoxylin/eosin-stained tissue sections from the primary tumor and metastatic lesions were evaluated. Prostatic carcinomas were subclassified based upon the presence of glandular, urothelial, squamoid, or sarcomatoid differentiation. We focused our analysis on dogs that differed with respect to morphologic features of the primary tumor, lifetime duration of testicular hormone exposure, and presence of skeletal metastases. RESULTS: The vast majority of canine prostate carcinomas affected elderly sexually intact dogs or dogs that underwent surgical castration after sexual maturity. Adenocarcinoma was the most frequent histologic type, although more than half of canine prostate carcinomas exhibited intratumoral heterogeneity. In many cases, primary tumors showed mixed morphology, characterized by two or more types of differentiation. Duration of testicular hormone exposure was significantly different between dogs with adenocarcinoma and dogs with mixed morphology tumor, but did not appear to influence the frequency or pattern of metastases. Overall, gross metastases were present in 80% of dogs with prostate carcinoma. Skeletal metastases were present in 22% of cases, and the predominantly axial skeletal distribution of these lesions was similar to that reported in men with prostate carcinoma. Young dogs were at highest risk for development of skeletal metastases. CONCLUSIONS: This study provides a more complete characterization of spontaneous prostate carcinoma of dogs in terms of morphologic heterogeneity, skeletal metastases, and the influence of testicular hormones. Prostate carcinoma in pet dogs provides an immunocompetent, autochthonous tumor system that mimics certain aspects of human prostate cancer. This spontaneous model may contribute to our understanding of the factors that regulate carcinogenesis within the aged prostate, and to the development of chemoprevention strategies or bone-targeted therapies.