RESUMO
BACKGROUND: The Gleason grading system in prostatectomy specimens following receipt of neoadjuvant therapy has been considered inaccurate. However, with continuing expansion of novel therapeutics, it is important to understand whether the Gleason system can be effectively utilized in this setting. The aim of this study was to assess the ability of the Gleason grading system to predict systemic progression among prostatectomy specimens treated with neoadjuvant hormone therapy (NHT). METHODS: This was a single-institution retrospective analysis from 1987 to 2009 of 13,427 patients who underwent radical prostatectomy (RP) without NHT and 1148 patients with NHT. NHT consisted of leuprolide alone (n = 415), antiandrogen therapy alone (n = 400) and combined treatment (n = 333). Kaplan-Meier analysis estimated 15-year systemic progression-free survival among NHT and non-NHT patients. Cox proportional hazard regression models estimated risk of systemic progression following RP according to NHT use and nonuse. RESULTS: Median duration of NHT was 3 months (interquartile range (IQR) 2-4) whereas median follow-up after RP was 8.3 years (IQR 5-10.8). NHT patients were more likely to be D'Amico high risk, have locally advanced pathologic T stage (≥ pT3), pathologic Gleason scores (GS) of 8-10 and lymph node involvement (P<0.0001 for all). NHT use was associated with lower rates of positive surgical margins, more downgrading to pT0 and less GS upgrading from biopsy (P ≤ 0.001 for all). GS could not be assigned to only 3% of NHT patients. On multivariate analysis, pathologic GS remained a predictor of systemic progression (SP) following NHT (hazard ratio (HR) 1.6, P = 0.005), but the association was less strong compared with non-NHT patients (HR 2.9, P < 0.0001). CONCLUSIONS: Utilization of the Gleason system appears feasible among hormonally pretreated prostatectomy specimens and shows continued prognostication for systemic progression. Confirmatory investigations are needed before the Gleason system can be reliably applied in the setting of neoadjuvant therapy.
Assuntos
Gradação de Tumores , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Idoso , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Quimioterapia Adjuvante , Terapia Combinada , Progressão da Doença , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Modelos de Riscos Proporcionais , Prostatectomia , Neoplasias da Próstata/mortalidade , Estudos RetrospectivosRESUMO
PURPOSE: Previous studies have suggested that increased p53 expression is associated with advanced stage and biologically aggressive (chemotherapy resistant) Wilms tumors. We decided to test the hypothesis that increased immunopositivity of p53 is associated with biological aggressiveness in patients with histologically favorable Wilms tumors. MATERIALS AND METHODS: We reviewed the charts of all patients with unilateral Wilms tumor treated at our institution between 1976 and 2001. Histological characteristics, tumor stage, clinical course and p53 expression as determined by immunohistochemical analysis were determined. All immunohistological evaluations were performed on tissue obtained before administration of chemotherapy. RESULTS: A total of 63 cases of unilateral histologically favorable Wilms tumor were assessed. Five cases (8%) were p53 positive. No significant relationship to p53 expression or stage at presentation was noted in 1 of 21 (5%) stage 1, 3 of 21 (14%) stage 2, 1 of 11 (9%) stage 3 and 0 of 10 stage 4 tumors positive for up-regulation of p53. Of the 5 patients with up-regulated p53 expression 1 (20%) had documented disease progression or relapse while on standard National Wilms Tumor Study chemotherapy. Of the 58 patients who were p53 negative 10 (17%) had disease progression or relapse while on standard National Wilms Tumor Study chemotherapy (p >0.3). CONCLUSION: In contrast to previously published studies, we found no correlation of p53 expression to either tumor stage at presentation (p >0.3) or prognosis (p >0.3) in individuals with histologically favorable Wilms tumor assessed for immunopositivity before administration of chemotherapy.
Assuntos
Neoplasias Renais/química , Neoplasias Renais/patologia , Proteína Supressora de Tumor p53/análise , Tumor de Wilms/química , Tumor de Wilms/patologia , Criança , Pré-Escolar , Seguimentos , Humanos , Lactente , Neoplasias Renais/imunologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Proteína Supressora de Tumor p53/imunologia , Tumor de Wilms/imunologiaRESUMO
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.
Assuntos
Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Adenocarcinoma/sangue , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Glândulas Seminais/patologia , Análise de SobrevidaRESUMO
DNA ploidy and proliferation have been shown in several studies to be prognostic markers for prostate cancer. Flow cytometry (FCM) is often used in the determination of ploidy and proliferation. However, FCM cannot readily distinguish among benign epithelium, stromal and inflammatory cells, high grade prostatic intraepithelial neoplasia (HGPIN), and cancer cells. In this study, we evaluated H&E histologic features of 322 radical prostatectomy formalin-fixed, paraffin-embedded tissue blocks used for determining DNA ploidy, percent S-phase (%S), and %S + %G2M by FCM. The microscopic findings included Gleason score, extent of cancer and HGPIN in the tissue block, and presence of a needle track. The amount of cancer in the block was expressed as a percentage of the total tissue surface area in quartiles: < or =25%, 26-50%, 51-75%, and > or =76%. The extent of HGPIN was recorded in rough 5% intervals. Needle track effect was defined as a combination of fibrohistiocytic reaction, fibrin clot, granuloma formation, and chronic inflammation. The associations between these histologic features and DNA ploidy and proliferation (%S and %S + %G2M) were assessed. In multivariate analyses, Gleason score, the amount of tumor in the tissue block, and the extent of HGPIN were significantly associated with ploidy. Gleason score was the only parameter significantly associated with the proliferation measure of %S. If we included %G2M as part of the proliferative fraction of the histogram, however, both Gleason score and the amount of tumor in the block were significantly associated with this measure of proliferation. The presence of a needle track was not significantly associated with DNA ploidy, %S, or %S + %G2M. In summary, prostate cancer DNA ploidy and proliferation results assessed by FCM in paraffin-embedded tissue blocks were associated with the Gleason score, amount of cancer in the tissue block, and extent of HGPIN. However, the presence of a needle track was not associated with the FCM results.
Assuntos
DNA de Neoplasias/genética , Ploidias , Neoplasias da Próstata/genética , Adulto , Idoso , Divisão Celular , Citometria de Fluxo , Fase G2 , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prostatectomia , Neoplasias da Próstata/patologia , Fase SRESUMO
BACKGROUND: DNA ploidy analysis of prostate carcinoma is a generally accepted prognostic marker, particularly when tumors are extraprostatic at the time of surgery. In the past decade, the DNA content of prostate carcinoma frequently has been assessed in needle biopsy specimens based on the assumption that ploidy, in conjunction with serum prostate specific antigen (PSA) and Gleason score, provides valuable pretreatment information. METHODS: Between 1995 and 1998, the authors identified a consecutive series of 454 prostate carcinomas, verified by needle biopsies and followed by radical retropubic prostatectomies (RRP). Based on the needle biopsies, DNA ploidy and MIB-I immunostaining were measured by digital image analysis (DIA). The authors also quantified the percent of nuclei in four categories from the DNA histograms. The DIA data were combined with the age of the patient at diagnosis, the serum PSA, Gleason score, percent cores and percent surface area positive for carcinoma, and status of perineural invasion in multivariate models using tumor volume and risk of extraprostatic extension (EPE) at RRP as the outcome variables. RESULTS: Joint predictors of tumor volume at RRP were the percent cores positive for carcinoma (P < 0.0001), serum PSA (P < 0.0001), the percent surface area positive for carcinoma (P < 0.0001), and the percent nuclei classified by DNA quantification to be in the "S-phase" category (P = 0.03). Joint predictors of risk of EPE were the percent cores positive for carcinoma (P = 0.0004), a Gleason score of 7 (P < 0.0001), a Gleason score of 8 or 9 (P < 0.0001), serum PSA (P = 0.006) and perineural invasion (P = 0.02). CONCLUSIONS: After adjusting for traditional prognostic markers, DNA ploidy interpretation and MIB-I quantitation of prostate carcinoma did not appear to jointly predict either outcome variable in the multivariate models. However, a quantitative measure related to both ploidy and proliferation, the percent of nuclei in the putative "S-phase" category from the DIA histograms, was found to jointly predict for tumor volume.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma/patologia , Invasividade Neoplásica , Ploidias , Neoplasias da Próstata/patologia , Adulto , Idoso , Biópsia por Agulha , Carcinoma/cirurgia , Ciclo Celular , Divisão Celular , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos RetrospectivosRESUMO
Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with decreased survival. High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA. Intracapsular carcinoma has a benign clinical course. Significant prognostic factors in CXPA include tumor stage, grade, proportion of carcinoma, extent of invasion, and proliferation index.
Assuntos
Adenoma/patologia , Neoplasias das Glândulas Salivares/patologia , Actinas/análise , Adenocarcinoma/patologia , Adenoma/química , Adenoma/mortalidade , Adulto , Idoso , Antígeno Carcinoembrionário/análise , Divisão Celular , DNA de Neoplasias/análise , Feminino , Proteína Glial Fibrilar Ácida/análise , Humanos , Queratinas/análise , Masculino , Pessoa de Meia-Idade , Mucina-1/análise , Invasividade Neoplásica , Prognóstico , Receptor ErbB-2/análise , Estudos Retrospectivos , Proteínas S100/análise , Ductos Salivares/patologia , Neoplasias das Glândulas Salivares/química , Neoplasias das Glândulas Salivares/mortalidade , Taxa de Sobrevida , Proteína Supressora de Tumor p53/análise , Vimentina/análiseRESUMO
BACKGROUND & AIMS: The identification of any high-grade dysplasia (HGD) in Barrett's esophagus has been considered to be an indication for esophagectomy because of the increased risk of cancer. The aim of this study was to determine if a limited extent of HGD has the same potential for cancer as diffuse HGD. METHODS: A retrospective cohort study was performed to assess the risk of developing adenocarcinoma in relationship to the extent of HGD found on endoscopic surveillance. The extent of HGD was defined as focal if cytologic and/or architectural changes of HGD were limited to a single focus of 5 or fewer crypts and diffuse if more than 5 crypts were involved in a single biopsy specimen or if HGD involved more than one biopsy fragment. The relative risk of cancer was assessed using a Cox proportional hazard model, and cancer-free survival was determined using survival curves. RESULTS: Sixty-seven patients with diffuse HGD and 33 with focal HGD satisfied selection criteria. Cancer-free survival rates at 1 and 3 years were 93% and 86% for focal HGD compared with 62% and 44% for diffuse HGD (P < 0.001). On univariate analysis, extent of HGD (relative risk, 5.36; 95% confidence interval, 1.84-15.56), nodularity on endoscopy (relative risk, 3.98; 95% confidence interval, 1.97-8.04), and lack of acid suppression (relative risk, 2.48; 95% confidence interval, 1.16-5.28) were associated with an increased risk of esophageal adenocarcinoma. Diffuse HGD had a 3.7-fold increase in the risk of esophageal cancer compared with focal HGD (P = 0.02) on multivariate analysis. CONCLUSIONS: Patients with focal HGD are less likely to have cancer during the first year after diagnosis or on subsequent follow-up compared with diffuse HGD.
Assuntos
Adenocarcinoma/etiologia , Esôfago de Barrett/patologia , Neoplasias Esofágicas/etiologia , Esôfago/patologia , Adulto , Idoso , Esôfago de Barrett/complicações , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
Between 1986 and 1996, 35 patients with a diagnosis of hamartoma of the breast were seen at the Mayo Clinic. One patient had two lesions. The mean age was 50 years (range 21-86 years). Hamartomas were clinically identified as a palpable lump in 18 cases (11 were detected by the patient and 7 by a physician). The other 18 were identified mammographically. Twenty-four lesions were in the left breast and 12 were in the right breast; 39% were located in the upper outer quadrant. Mammographically most hamartomas were ovoid, and the lesions were well circumscribed. Sonographically they were all solid, but 24% showed cystic areas. Pathologically the mean greatest diameter was 3.2 cm (range 1.0-7.5 cm). All but one lesion showed circumscription. The mean percentage of fibrous tissue was 78% (range 5-95%), fat 13% (range 0-95%), and epithelium 9% (range 1.0-60%). Calcifications were seen in four lesions. Ductal hyperplasia was present in 27% and adenosis in 70% of lesions. Twelve percent of patients had coexistent fibroadenomas.
Assuntos
Neoplasias da Mama/patologia , Hamartoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Feminino , Hamartoma/diagnóstico por imagem , Humanos , Prontuários Médicos , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , UltrassonografiaRESUMO
We report the clinical, morphologic, immunophenotypic, and ploidy findings of seven cases of serous borderline tumor of the paratestis. Mean patient age was 56 years (range, 14-77 years), and the clinical presentation was that of a testicular mass. Tumors ranged in size from 1 to 6 cm (mean, 3.5 cm). Six tumors arose from the tunica albuginea, and two of these tumors were intratesticular. One tumor arose from the tunica vaginalis. Serous borderline tumor of the paratestis is histologically identical to its ovarian counterpart. The tumors were cystic with numerous intracystic blunt papillae lined by stratified epithelial cells with minimal to mild cytologic atypia. Psammoma bodies were present in two cases. In all cases, the neoplastic cells stained strongly and diffusely for cytokeratin 7, estrogen receptor, and CD15, and six of seven cases were positive for progesterone receptor and MOC-31. The cells did not stain for cytokeratin 20, carcinoembryonic antigen, calretinin, and HER2/neu. Proliferative activity, as assessed by MIB-1 staining, ranged from 1.3% to 10% (mean, 5.5%). Five of six tumors were diploid, and one was tetraploid. Patients were treated by radical orchiectomy and followed up from 4 months to 18 years (mean, 48 months; median, 8.5 months). No recurrences or metastases occurred. Serous borderline tumor of the paratestis is morphologically and immunophenotypically identical to ovarian serous borderline tumor. To date, no serous borderline tumor of the paratestis reported in the literature or in our series has recurred or metastasized after resection.
Assuntos
Cistadenoma Seroso/patologia , Neoplasias Testiculares/patologia , Adenocarcinoma/secundário , Tumor Adenomatoide/patologia , Adolescente , Adulto , Idoso , Antígenos Nucleares , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Cistadenocarcinoma Seroso/patologia , Cistadenoma Papilar/patologia , Cistadenoma Seroso/genética , Cistadenoma Seroso/metabolismo , DNA de Neoplasias/análise , Epididimo/patologia , Humanos , Citometria por Imagem , Processamento de Imagem Assistida por Computador , Antígeno Ki-67 , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Ploidias , Neoplasias da Próstata/patologia , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismoRESUMO
OBJECTIVE: To evaluate the accuracy of digital image analysis (DIA) for distinguishing between benign and malignant strictures of the biliary tract. PATIENTS AND METHODS: Our pathology databank was used to identify all biliary brush cytology specimens obtained during endoscopic retrograde cholangiopancreatography between June 1997 and June 1999. Corresponding medical records were reviewed to determine whether patients had benign or malignant strictures. Strictures were further classified into benign strictures with negative routine cytology, malignant strictures with negative routine cytology, and malignant strictures with positive routine cytology. Papanicolaou-stained smears of available brush cytology specimens were destained and then restained with Feulgen dye. Nuclear images were quantified for DNA content without knowledge of stricture type. DNA histograms were generated and ploidy results compared with the class of stricture. RESULTS: We analyzed 27 specimens from 69 confirmed benign or malignant strictures. Assuming that the presence of any aneuploid cells indicated malignancy, the sensitivity of DIA was 85%. Furthermore, aneuploid cells were detected by DIA in 13 of 16 specimens in which routine cytology was unrevealing. CONCLUSION: Ploidy assessment by DIA has potential to enhance the sensitivity of diagnosing malignant strictures compared with routine cytology alone.
Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Análise Citogenética , Aumento da Imagem/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
We analyzed a series of adrenocortical neoplasms to compare the clinicopathologic features and the expression of insulin-like growth factor-2 (IGF-2) in adrenocortical adenomas and carcinomas. IGF-2 is a growth factor commonly expressed in many tumors including adrenal cortical and medullary neoplasms. Formalin-fixed paraffin-embedded tissues from 64 adrenocortical adenomas and 67 adrenocortical carcinomas were analyzed. The carcinomas were histologically graded from 1 to 4 based on mitotic activity and necrosis. Tumor weight, size, and follow-up information were obtained by chart review. Expression of IGF-2 was detected by immunohistochemistry with the avidin-biotin-peroxidase complex method and a monoclonal antibody against IGF-2. Adrenocortical carcinomas were larger (mean: 13.1 cm, 787 g) than adenomas (mean: 4.2 cm, 52 g) (p < 0.001). Inpatients with adrenocortical carcinomas, high tumor grade (3 or 4) (p = 0.01) was associated with decreased survival. Expression of IGF-2 was higher in adrenocortical carcinomas than in adenomas (p < 0.001). These results show that tumor size and weight along with expression of IGF-2 protein are useful features to assist in distinguishing between adrenocortical adenomas and carcinomas, and that high tumor grade is a predictor of survival in adrenocortical carcinomas. However, single immunohistochemical markers such as IGF-2 or single histopathologic features cannot by themselves separate adrenocortical adenomas from carcinomas, and a combination of clinical, gross, and microscopic features are needed to establish the diagnosis in difficult cases.
Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Adenoma Adrenocortical/metabolismo , Adenoma Adrenocortical/patologia , Carcinoma Adrenocortical/metabolismo , Carcinoma Adrenocortical/secundário , Fator de Crescimento Insulin-Like II/metabolismo , Adolescente , Neoplasias do Córtex Suprarrenal/mortalidade , Adenoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Mitose , Necrose , Análise de Sobrevida , Taxa de SobrevidaRESUMO
BACKGROUND AND AIM OF THE STUDY: Elevated serum serotonin is associated with carcinoid heart disease, the hallmark of which is valvular thickening. Yet, the mechanistic role of serotonin in carcinoid heart disease is poorly understood. We postulated that serotonin has a direct mitogenic effect on cardiac valvular subendocardial cells, and that this effect is mediated by serotonin receptors. METHODS: The dose-dependent proliferative effects of serotonin (10(-8) to 10(-4)M) on cultured porcine aortic valve cells via a [3H]thymidine assay were determined in vitro. Serotonin receptor antagonist studies in culture were also performed using methiotepin, a 5HT1b antagonist, and ketanserin, a 5HT2 receptor antagonist, to determine the mechanism of serotonin action. The ex-vivo proliferation level in human carcinoid (n = 26) and normal valves (n = 10) was compared using proliferating cell nuclear antigen (PCNA) staining, a marker for proliferation. Identification and localization of specific 5HT receptor was assessed by immunostaining for serotonin receptors in the valves. RESULTS: Serotonin increased valvular proliferation in vitro in a dose-dependent manner (10-fold increase) (p <0.001), and this mitogenic effect was inhibited by methiotepin but not ketanserin. In human carcinoid heart valves the level of proliferation was 35-fold higher than in normal human valves (p <0.001). 5HT1b receptors were found only in the carcinoid valves, and not in the normal valves. CONCLUSION: Serotonin is a powerful mitogen for valvular subendocardial cells. The mitogenic effect is at least partly mediated via 5HT1b receptors. Subendothelial cell proliferation is significantly elevated in human carcinoid valves in vivo. The data suggest a mechanism whereby serotonin may contribute to valvular proliferation in carcinoid heart disease.
Assuntos
Doença Cardíaca Carcinoide/fisiopatologia , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Endocárdio/efeitos dos fármacos , Endocárdio/fisiopatologia , Sequestradores de Radicais Livres/farmacologia , Valvas Cardíacas/efeitos dos fármacos , Valvas Cardíacas/fisiopatologia , Receptores de Serotonina/efeitos dos fármacos , Serotonina/farmacologia , Animais , Doença Cardíaca Carcinoide/patologia , Relação Dose-Resposta a Droga , Endocárdio/patologia , Valvas Cardíacas/patologia , Humanos , Técnicas In Vitro , Ketanserina/farmacologia , Metiotepina/farmacologia , Receptores de Serotonina/fisiologia , Antagonistas da Serotonina/farmacologia , SuínosRESUMO
OBJECTIVE: To evaluate the presentation and prognosis of primary localized amyloidosis of the urinary bladder. PATIENTS AND METHODS: The medical records of 31 patients with primary localized amyloidosis of the urinary bladder were reviewed. Immunohistochemical amyloid typing was performed on bladder biopsy specimens from 27 patients. RESULTS: The median age of the 22 men and 9 women was 55 years. Twenty-four patients (77%) presented with gross hematuria (associated with irritative urinary tract symptoms in 6 patients), and 7 (23%) had only irritative lower urinary tract symptoms. Multiple bladder areas were involved in 20 patients (65%), a single area was involved in 8 (26%), and diffuse involvement was present in 3 (10%). Twenty-four patients had immunoglobulin light chain, and 3 had transthyretin-related amyloid. Local recurrences were common. None of the patients developed systemic amyloidosis. CONCLUSION: Primary localized amyloidosis of the urinary bladder can be easily confused with a neoplasm. Immunohistochemical amyloid typing is important. Transthyretin-related amyloid of the bladder requires no further work-up. Repeated work-ups for systemic amyloidosis are unnecessary for patients with light chain-related amyloidosis of the urinary bladder. Early eradication with fulguration or laser therapy is indicated. Cystoscopic follow-up is necessary.
Assuntos
Amiloidose/epidemiologia , Amiloidose/patologia , Doenças da Bexiga Urinária/epidemiologia , Doenças da Bexiga Urinária/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Amiloidose/cirurgia , Vermelho Congo , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Prognóstico , Estudos Retrospectivos , Distribuição por Sexo , Resultado do Tratamento , Doenças da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
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.
Assuntos
Recidiva Local de Neoplasia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Uretra/patologia , Idoso , Biópsia , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prostatectomia , Resultado do TratamentoRESUMO
PURPOSE: We determine the relative sensitivities of cytology and fluorescence in situ hybridization (FISH) for the detection of urothelial carcinoma. MATERIALS AND METHODS: A mixture of fluorescent labeled probes to the centromeres of chromosomes 3, 7 and 17, and band 9p21 (P16/CDKN2A gene) was used to assess urinary cells for chromosomal abnormalities indicative of malignancy. A total of 280 urine specimens from 265 patients, including 150 with a history of urothelial carcinoma and 115 without a history of urothelial carcinoma, were analyzed. FISH analysis was performed without prior knowledge of clinical findings, that is biopsy, cystoscopy and cytology results. A positive result was defined as 5 or more urinary cells with gains of 2 or more chromosomes. RESULTS: A total of 75 biopsies showed urothelial carcinoma at FISH analysis among the 265 patients. The sensitivity of urine cytology for pTa (36 cases), pTis (18) and pT1-pT4 (15) tumors was 47%, 78% and 60%, respectively, for an overall sensitivity of 58%. The sensitivity of FISH for pTa (37 cases), pTis (17) and pT1-pT4 (19) tumors was 65%, 100% and 95%, respectively, for an overall sensitivity of 81%. FISH was significantly more sensitive than cytology for pTis (p = 0.046), pT1-pT4 (p = 0.025), grade 3 (p = 0.003) and all tumors (p = 0.001). The specificity of cytology and FISH among patients without cystoscopic evidence of urothelial carcinoma and no history of urothelial carcinoma was 98% and 96%, respectively (p = 0.564). CONCLUSIONS: The sensitivity of FISH for the detection of urothelial carcinoma is superior to that of cytology, and the specificity of FISH and cytology for urothelial carcinoma are not significantly different. Further prospective studies are required but FISH has the potential to improve significantly the management of urothelial carcinoma.
Assuntos
Hibridização in Situ Fluorescente , Neoplasias Urológicas/diagnóstico , Centrômero , Progressão da Doença , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/diagnóstico , Urina/citologiaRESUMO
BACKGROUND & AIMS: Photodynamic therapy (PDT) is a technique for nonsurgical treatment of patients with dysplasia in Barrett's esophagus. The primary endpoint for PDT has been resolution of dysplasia. We studied the effect of PDT at the genetic level. METHODS: Archival material from 3 patients who had initial improvement in dysplasia after PDT but occurrence of high-grade dysplasia during follow-up was used. Biopsy specimens were analyzed for increased proliferation, aneuploidy, p53 protein overexpression, p53 mutations, and p16 promoter hypermethylation. RESULTS: Patients developed high-grade dysplasia 16, 28, and 37 months after PDT. In all cases, one or more genetic markers were positive after PDT treatment, whereas histology was downstaged consistently after therapy. Increasing genetic abnormalities were noted by the end of follow-up. CONCLUSIONS: Genetic abnormalities may persist after PDT despite phenotypical improvement of dysplasia. These patients may progress to high-grade dysplasia or develop adenocarcinoma. Histologic improvement in dysplasia is an inadequate endpoint for PDT in patients with Barrett's esophagus.
Assuntos
Esôfago de Barrett/tratamento farmacológico , Esôfago de Barrett/genética , Fotoquimioterapia , Idoso , Aneuploidia , Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Esôfago/patologia , Seguimentos , Humanos , Masculino , Metilação , Pessoa de Meia-Idade , Mutação Puntual/genética , Regiões Promotoras Genéticas , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Twenty-three cases of extraskeletal myxoid chondrosarcoma, evaluated at the Mayo Clinic between 1968 and 1996, were studied for clinicopathologic features, immunohistochemical profile, Ki-67 activity, and ploidy status to identify adverse prognostic factors. Females and males were equally affected, and the median age at diagnosis was 50 years. The tumors were located mainly in the lower extremities (83%), and the median tumor size was 9.5 cm. Sixteen tumors showed low cellularity (70%), and eight tumors had high mitotic activity (more than two per 10 high-power fields). The tumors were immunoreactive for vimentin (89%), synaptophysin (72%), epithelial membrane antigen (28%), and S-100 protein (17%). Nine tumors were diploid, three aneuploid, and one tetraploid. Mean Ki-67 activity was 11% (range, 1 to 45%). The 10-year overall survival rate was 78%. On univariate analysis, tumor size > or = 10 cm, high cellularity, presence of anaplasia or rhabdoid features, mitotic activity more than two per 10 high-power fields, Ki-67 > or = 10%, and Ki-67 "hot spot" > or = 25% were associated with decreased metastasis-free or overall survival. Ploidy status was not associated with any adverse outcome. The presence of any of these adverse prognostic factors can indicate the possibility of a more aggressive behavior in extraskeletal myxoid chondrosarcoma, and a closer follow-up is suggested.
Assuntos
Condrossarcoma/patologia , Ploidias , Neoplasias de Tecidos Moles/patologia , Adulto , Idoso , Biomarcadores Tumorais/análise , Condrossarcoma/química , Condrossarcoma/genética , Condrossarcoma/mortalidade , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Técnicas Imunoenzimáticas , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Proteínas de Neoplasias/análise , Prognóstico , Neoplasias de Tecidos Moles/química , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/mortalidade , Análise de Sobrevida , Taxa de SobrevidaRESUMO
Cytologic examination of body fluids is commonly performed in the clinical laboratory. Determination of the presence of malignancy may sometimes be difficult. In this study, we prospectively studied 60 body fluids with a panel of antibodies, including MOC-31, epithelial membrane antigen, carcinoembryonic antigen, B72.3, keratin, desmin, and CA-125. DNA and S-phase studies were performed both by flow cytometry and image analysis. Thirty-seven fluids were classified as benign and 23 were classified as malignant. The sensitivity of the antibodies for identification of carcinoma in descending order of percentage detection rate were MOC-31 (95%), epithelial membrane antigen (93%), B72.3 (84%), and carcinoembryonic antigen (80%). Desmin stained mesothelial cells in all cases. CA-125 gave similar results but was less specific. Flow cytometry detected 14 of 20 malignant fluids and image analysis 17 of 23 by identifying an aneuploid population. Benign reactive mesothelial cells were not aneuploid. Tetraploidy due to reactive mesothelial cells was found in 9 of 37 body fluids. Their S-phase fraction was low (average, 3.2%). Tetraploidy in malignant cells was distinguished from the reactive mesothelial cells by high S-phase (average, 25.95). S-phase had some use as a discriminating factor, because no benign reactive cases had more than 17%. However, 7 of 23 malignant cases had a value below 17%. DNA analysis by image was more sensitive and specific than flow. Either may be used when immunocytochemistry is nondiagnostic or cannot be performed.
Assuntos
Biomarcadores Tumorais/análise , Líquidos Corporais/citologia , DNA de Neoplasias/análise , Citometria de Fluxo/métodos , Citometria por Imagem/métodos , Proteínas de Neoplasias/análise , Neoplasias/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias/química , Neoplasias/genética , Ploidias , Estudos Prospectivos , Fase S/genética , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: The object of this study was to assess the association of histologic, cytokinetic, and molecular variables in preoperative endometrial samples with extrauterine disease, recurrence, and survival among patients with endometrial cancer. STUDY DESIGN: In a case-cohort study of 125 women, ploidy, S-phase fraction, proliferative index, deoxyribonucleic acid index, proliferating cell nuclear antigen, MIB-1 proliferation marker, p53 tumor suppressor gene, and cytoplasmic HER-2/neu oncogene and bcl-2 expressions were quantitated. RESULTS: A model with only one independent term predicted progression-free survival; that variable was p53 (P <. 0001; relative risk, 5.60). A model with two independent terms predicted disease-related survival; these variables were p53 (P =. 0002; relative risk, 7.39) and MIB-1 (P =.03; relative risk, 3.27). Among patients with tumors with both p53 and MIB-1 expression exceeding 33%, a total of 32% had died of disease by 2 years. A model for predicting extrauterine disease selected two independent variables: p53 (odds ratio, 3.20; P =.01) and ploidy (odds ratio, 2. 16; P =.04). An advanced surgical stage was encountered in 26% to 35% of cases in which either the p53 expression exceeded 33% or the deoxyribonucleic acid content was nondiploid and in 53% of cases in which both variables were unfavorable. CONCLUSIONS: Preoperative evaluation of quantifiable cytokinetic and molecular variables can assist in identifying tumor types that are predisposed toward a more aggressive clinical course.
Assuntos
Neoplasias do Endométrio/terapia , Adulto , Idoso , Antígenos Nucleares , Estudos de Coortes , DNA/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Antígeno Ki-67 , Pessoa de Meia-Idade , Modelos Teóricos , Metástase Neoplásica , Estadiamento de Neoplasias , Proteínas Nucleares/metabolismo , Razão de Chances , Ploidias , Prognóstico , Análise de Regressão , Fatores de Risco , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: To the authors' knowledge, there is no previous report of squamous papilloma of the urinary tract. It is uncertain whether there is a correlation between squamous papilloma, condyloma acuminatum, and verrucous carcinoma. METHODS: The authors evaluated the clinical and pathologic features of squamous papilloma (5 of the bladder, 2 of the urethra), condyloma acuminatum (3 cases), and verrucous carcinoma (3 cases) of the urinary bladder and performed human papillomavirus (HPV) DNA in situ hybridization studies to determine whether HPV was a common feature shared by these lesions. In addition, DNA ploidy evaluation by image cytometry and p53 immunohistochemical staining were performed. RESULTS: Squamous papilloma of the urinary tract occurred in elderly women and followed a benign clinical course with infrequent recurrence. All squamous papillomas were HPV DNA negative and DNA diploid with no or minimal p53 nuclear accumulation. Condyloma acuminata of the bladder contained HPV DNA, increased p53 protein expression, and aneuploid DNA content. All three cases of condyloma acuminata were associated with coexistent condylomata of the external genitalia, and two required pelvic exenteration for uncontrolled expansile growth. Verrucous carcinoma of the bladder occurred in elderly patients. All three cases of verrucous carcinoma were negative for HPV DNA and DNA aneuploid, and they exhibited consistent p53 expression. CONCLUSIONS: These data indicate that squamous papilloma is a distinct entity not related to condyloma or verrucous carcinoma. These lesions are benign, HPV DNA negative, DNA diploid, and they lack p53 overaccumulation.