RESUMO
BACKGROUND: Molecular markers are currently being utilized as sensitive prognosticators of cancer patient outcome. We sought to identify prognostic biomarkers for complex karyotype soft tissue sarcoma (STS). MATERIALS AND METHODS: A large (n = 205) clinically annotated tissue microarray (TMA) was constructed and immunostained for several tumor-related markers. Staining was scored via an automated Ariol image analysis system; data were statistically analyzed to evaluate the correlation of clinicopathological and molecular variables with overall survival (OS) and local recurrence. RESULTS: Multivariable analysis identified older age [hazard ratio (HR) 1.62, P < 0.0001], nonextremity location (HR 2.95, P = 0.001), high tumor grade (HR 2.5, P = 0.02), and increased matrix metalloproteinase (MMP) 2 expression (HR 1.74, P = 0.04) as predictors for poor OS. Similarly, older age (HR 1.51, P = 0.008), nonextremity location (HR 4.09, P = 0.001), and increased MMP2 expression (HR 6.28, P = 0.006) were all found to correlate with shorter local recurrence-free interval. High nuclear p53 expression was associated with shorter STS local recurrence-free interval, with a trend toward significance. CONCLUSIONS: Data presented indicate that a clinically annotated TMA can be utilized to identify STS-related prognostic markers. Specifically, MMP2 and nuclear p53 should be further evaluated for their potential inclusion in complex karyotype STS staging systems.
Assuntos
Biomarcadores Tumorais/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Sarcoma/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Cariotipagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Estudos Prospectivos , Sarcoma/diagnóstico , Taxa de Sobrevida , Análise Serial de TecidosRESUMO
BACKGROUND: Data suggest that the current American Joint Committee on Cancer (AJCC) soft tissue sarcoma (STS) staging criteria merit further evaluation. We sought to identify and validate factors as enhanced descriptors of STS clinical behavior. METHODS: Prospectively accrued data were analyzed for 1,091 AJCC stage I to III primary STS patients who had complete macroscopic resection at our institution from 1996 to 2007. Study factors were examined by univariable and multivariable analyses to identify independent prognostic factors for disease related mortality and overall survival (OS). RESULTS: In contrast to the current AJCC STS staging system, which stratifies size into T1 (=5 cm) and T2 (>5 cm) groups, we demonstrated three distinct cohorts (P < 0.0001): T1 (=5 cm; 5-year OS 85%), T2 (5 to 15 cm; OS 68%), and T3 (>15 cm; OS 52%). A two-category system of histologic grade was demonstrably as informative as the current four histologic grade AJCC system. A multivariable Cox proportional hazard model identified tumor size (5 to 15 cm vs. =5 cm, P = 0.03; or >15 cm vs. =5 cm; P < 0.0001), nonextremity primary site (P = 0.0016), disease of high histologic grade (P = 0.001), specific histology (P = 0.001), and margin positivity (P < 0.0001) as statistically significant adverse independent prognostic factors. Recurrence during follow-up was the most significant risk factor for STS-specific mortality (P < 0.0001). CONCLUSION: Tumor size and grade in the AJCC STS staging system need revision; moreover, primary site, histologic subtype, margin status, and recurrence offer additional relevant prognostic insight. Incorporation of these factors may enhance the AJCC staging system, thereby further facilitating individualized therapeutic strategies for STS patients.
Assuntos
Recidiva Local de Neoplasia/patologia , Sarcoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Sarcoma/classificação , Sarcoma/terapia , Taxa de SobrevidaRESUMO
BACKGROUND: Division of retroperitoneal liposarcoma (RPLS) into well-differentiated (WD) and dedifferentiated (DD) subtypes is established; however, WD and DD are usually treated similarly. We hypothesized that WD and DD have distinct biological behaviors mandating different treatments. METHODS: A prospective sarcoma database identified all primary/recurrent RPLS treated between 1996 and 2007: 77 DD (52%) and 58 WD (39.2%) patients were analyzed for recurrence rate, recurrence free survival (RFS), and overall survival (OS). RESULTS: At presentation, WD were mostly primary whereas DD were mostly recurrent (75.9% versus 58.4%; p = 0.04). A significant proportion of DD (37.7%) received chemotherapy compared to WD (1.7%; p < 0.0001). Multivisceral resection was more common in DD versus WD (45.5% versus 31%; p = 0.01). Gross total resection rates were equivalent (WD: 86.2%; DD: 85.7%). Overall and local recurrence were higher in DD versus WD (82.2% versus 50% and 71.2% versus 46.3%; p < 0.0001). Only 3.7% WD recurred as high grade metastatic disease. Median time to recurrence was 55.5 months in WD versus 13.5 months in DD (p < 0.0001). RFS and OS (1, 2, and 5 year) were higher in WD than DD (80.3% versus 55.9%; 65.1% versus 34.1%; 41.9% versus 7.8%; p < 0.0001) and (98% versus 88.1%; 95.6% versus 71.9%; 92.1% versus 36.5%; p < 0.0001) respectively. CONCLUSION: WD and DD have distinct biological behaviors. Gross total resection is achievable in most WD; unlike DD, high-grade recurrence is uncommon. Treatment should therefore reflect these biologic differences by maximizing survivorship while avoiding unnecessarily extensive multivisceral resection. SYNOPSIS: The biological behaviors of well-differentiated and dedifferentiated liposarcomas differ significantly. This article presents outcomes of two different surgical approaches that were implemented at the UTMDACC, treating these tumors as different disease entities.
Assuntos
Lipossarcoma/patologia , Lipossarcoma/cirurgia , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados como Assunto , Feminino , Humanos , Lipossarcoma/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Retroperitoneais/mortalidade , Análise de SobrevidaRESUMO
Persistent shortage of kidneys for transplantation has forced most transplant centers to include procurement and use of kidneys from older donors. It is not clear whether the optimal use of these kidneys involve age-matching to the recipient. The aim of this study was to evaluate the clinical outcome of older cadaveric kidneys (>60 years), transplanted to young recipients (<50 years) and older recipients (>60 years). From 1989 through 2002, 252 first kidney grafts were procured from donors above the age of 60; 149 of the recipients to these grafts were above 60 years and 45 recipients were below 50. Minimum follow-up time was 12 months. Variables for waiting time to transplantation, DR mismatches, PRA, dialysis prior to transplantation, episodes of acute rejection, number of steroid-resistant rejections, creatinine levels, cold ischemia time, and causes of graft loss did not differ between the two groups. There was no significant difference in graft survival for young and older recipients receiving kidney from donors above 60 years of age. Graft survival at 1 year for young recipients was 90% and for older recipients 93% (NS). Five-year graft survival was 72% and 79%, respectively (NS). However, there was a significant positive effect on long-term graft survival if the donor kidney was less than 50 years. From our data, there is no evidence that age-matching of older donors has any beneficial effect on graft survival in kidney transplantation.