Independent Predictor Of Tumor Progression Research Articles

The pretreatment platelet count is an independent predictor of tumor progression in patients undergoing transcatheter arterial chemoembolization with hepatitis B virus-related hepatocellular carcinoma.

To explore the prognostic value of the pretreatment platelet (PLT) count in patients undergoing transcatheter arterial chemoembolization (TACE) with hepatocellular carcinoma (HCC). We prospectively analyzed 317 hepatitis B virus-related HCC patients undergoing TACE. Time to progression (TTP) was selected to evaluate the clinical significance of PLT level in HCC patients. PLT was the only parameter showing statistical significance of all the clinical characteristics between two distinct tumor response groups. After ruling out cirrhosis as a potential major confounding factor, the conclusion was further established. Higher pretreatment PLT level, portal vessel invasion and higher stratification of α-fetoprotein level were independently associated with longer TTP. The prognostic score model combining the three risk factors revealed that higher risk scores might mean shorter TTP. The pretreatment PLT level is a potentially useful biomarker to predict the prognostic outcomes in HCC patients undergoing TACE and deserves to be further explored in subsequent works.

Histogram analysis of apparent diffusion coefficient predicts response to radiofrequency ablation in hepatocellular carcinoma.

ObjectiveThe aim of this study was to predict tumor progression in patients with hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) using histogram analysis of apparent diffusion coefficients (ADC).MethodsBreath-hold diffusion weighted imaging (DWI) was performed in 64 patients (33 progressive and 31 stable) with biopsy-proven HCC prior to RFA. All patients had pre-treatment magnetic resonance imaging (MRI) and follow-up computed tomography (CT) or MRI. The ADC values (ADC10, ADC30, ADCmedian and ADCmax) were obtained from the histogram’s 10th, 30th, 50th and 100th percentiles. The ratios of ADC10, ADC30, ADCmedian and ADCmax to the mean non-lesion area-ADC (RADC10, RADC30, RADCmedian, and RADCmax) were calculated. The two patient groups were compared. Key predictive factors for survival were determined using the univariate and multivariate analysis of the Cox model. The Kaplan-Meier survival analysis was performed, and pairs of survival curves based on the key factors were compared using the log-rank test. ResultsThe ADC30, ADCmedian, ADCmax, RADC30, RADCmedian, and RADCmax were significantly larger in the progressive group than in the stable group (P<0.05). The median progression-free survival (PFS) was 22.9 months for all patients. The mean PFS for the stable and progressive groups were 47.7±1.3 and 9.8±1.3 months, respectively. Univariate analysis indicated that RADC10, RADC30, and RADCmedian were significantly correlated with the PFS [hazard ratio (HR)=31.02, 43.84, and 44.29, respectively, P<0.05 for all]. Multivariate analysis showed that RADCmedian was the only independent predictor of tumor progression (P=0.04). And the cutoff value of RADCmedian was 0.71. ConclusionsPre-RFA ADC histogram analysis might serve as a useful biomarker for predicting tumor progression and survival in patients with HCC treated with RFA.

Chromosome 9p deletions are an independent predictor of tumor progression following nephrectomy in patients with localized clear cell renal cell carcinoma

ObjectivesChromosome 9p deletions have been observed in 14% to 36% of patients with clear cell renal cell carcinoma (ccRCC) and are associated with advanced-stage tumors. We evaluated whether chromosome 9p deletions are an independent predictor of worse outcomes in patients with localized ccRCC. Materials and methodsIn this retrospective study, tumor samples from 94 patients with ccRCC NX-0 M0 who underwent radical nephrectomy or conservative renal surgery were analyzed using a fluorescence in situ hybridization technique. ResultsThe median follow-up period was 11.7 years, and 9p deletions were identified in 15% of cases. The cancer-specific survival rate estimated at 5 and 10 years was 99% and 96%, respectively, for patients without such chromosomal losses and 71% and 57% in patients with a loss of 9p (P<0.001). Chromosome 9p deletions were an independent prognostic factor in a multivariate analysis, increasing the risk of death due to disease by 28-fold (95% CI: 5–155, P<0.001). In patients with a low risk of progression, i.e., a low Stage, Size, Grade, and Necrosis score (0–2), low risk according to the University of California at Los Angeles Integrated Staging System, and low risk according to the pathological triad used at University of Sao Paulo, tumors with 9p deletions were significantly associated with a poorer cancer-specific survival at 10 years: 70%, 67%, and 67% vs. 98%, 97%, and 98%, respectively, in patients without 9p deletions. ConclusionChromosome 9p deletions independently establish a poorer prognosis for patients with localized ccRCC, providing further relevant clinical information that may improve the predictive ability of the main prognostic systems currently in use.

Copy Number Gain of 1q25 Predicts Poor Progression-Free Survival for Pediatric Intracranial Ependymomas and Enables Patient Risk Stratification: A Prospective European Clinical Trial Cohort Analysis on Behalf of the Children's Cancer Leukaemia Group (CCLG), Société Française d'Oncologie Pédiatrique (SFOP), and International Society for Pediatric Oncology (SIOP)

The high incidence of recurrence and unpredictable clinical outcome for pediatric ependymoma reflect the imprecision of current therapeutic staging and need for novel risk stratification markers. We therefore evaluated 1q25 gain across three age- and treatment-defined European clinical trial cohorts of pediatric intracranial ependymoma. Frequency of 1q gain was assessed across 48 ependymomas (42 primary, 6 recurrent) using Affymetrix 500K single-nucleotide polymorphism arrays. Gain of 1q25 was then evaluated by interphase FISH across 189 tumors treated on the Children's Cancer Leukaemia Group/International Society for Pediatric Oncology (SIOP) CNS9204 (n = 60) and BBSFOP (n = 65) adjuvant chemotherapy trials, or with primary postoperative radiotherapy (SIOP CNS9904/RT, n = 64). Results were correlated with clinical, histologic, and survival data. Gain of 1q was the most frequent imbalance in primary (7/42, 17%) and recurrent ependymomas (2/6, 33%). Gain of 1q25 was an independent predictor of tumor progression across the pooled trial cohort [HR = 2.55; 95% confidence interval (CI): 1.56-4.16; P = 0.0002] and both CNS9204 (HR = 4.03; 95% CI: 1.88-8.63) and BBSFOP (HR = 3.10; 95% CI: 1.22-7.86) groups. The only clinical variable associated with adverse outcome was incomplete tumor resection. Integrating tumor resectability with 1q25 status enabled stratification of cases into disease progression risk groups for all three trial cohorts. This is the first study to validate a prognostic genomic marker for childhood ependymoma across independent trial groups. 1q25 gain predicts disease progression and can contribute to patient risk stratification. We advocate the prospective evaluation of 1q25 gain as an adverse marker in future international clinical trials.

Snail expression is an independent predictor of tumor recurrence in superficial bladder cancers

Background Epithelial-mesenchymal transition (EMT) is known to play an important role in the development of tumor invasion and progression in tumors of epithelial origin. Objectives Our aim was to investigate the role of Snail transcription repressor family members in human bladder pathogenesis. Material and methods We evaluated levels of Snail and Slug in 87 patients who received transurethral resection of a transitional cell carcinoma at our institution during the period from June 1999 until November 2003. Immunohistochemistry was performed on tissue microarrays, and expression correlated with pathological variables and clinical outcomes. Degree and intensity of Snail and Slug staining was quantified by immunohistochemistry. Results There was no apparent enrichment in strong vs. weak staining for either Snail (43.7% vs. 56.3%) or Slug (46% vs. 54%) in the superficial bladder tumors. Univariate analysis determined that tumor focality and Snail expression were significantly associated with tumor recurrence ( P < 0.05). Only for tumor focality did such a relationship exist when assessing tumor progression. Multivariate analysis using the Cox's proportional hazards model revealed similar results to that of the univariate analysis. Snail expression ( P = 0.038) and tumor focality ( P = 0.011) were independent and significant prognostic factors for tumor recurrence in all patients. However, only tumor focality was an independent predictor of tumor progression ( P = 0.034). Conclusions High expression of Snail in superficial bladder tumors is a strong predictor of tumor recurrence enhancing risk stratification and prognostication.

Evaluation of neuroendocrine staining and androgen receptor expression in incidental prostatic adenocarcinoma: Prognostic implications

Objectives To identify neuroendocrine cells and androgen receptors (ARs), possible predictors of cancer progression, in a series of untreated patients with incidental Stage T1a prostate cancer (PCa). Neuroendocrine cells may exert a dynamic role in the microenvironment of PCa. The AR is thought to have a central role in the propagation of prostate carcinogenesis. Methods Prostatectomy specimens from 81 patients with Stage T1a PCa were available for analysis. Neuroendocrine cells were detected by immunohistochemistry using antibodies to chromogranin A (CgA) and neuron-specific enolase, and the antibody against AR enabled the evaluation of the nuclear AR status. Tumor cell proliferation was assessed with the Ki-67 labeling index using MIB-1 antibody. The patients were followed up for a mean of 63.9 months, and a subsequent rise in prostate-specific antigen or positive digital rectal examination findings confirmed by biopsy was considered disease progression. Results Of the 81 specimens, 62 (76.54%) were positive for CgA and/or neuron-specific enolase and 19 (23.46%) were negative. A statistically significant correlation was found between CgA positivity and tumor dedifferentiation ( P = 0.002). Well-differentiated tumors revealed an overexpression of ARs ( P <0.005). On multivariate analysis, worsening tumor differentiation emerged as the only independent predictor of progression-free survival ( P = 0.041); however, only CgA positivity was an independent predictor of tumor progression in well and moderately differentiated tumors ( P = 0.038). Conclusions The results of this study suggest that CgA may represent a useful marker for subsequent aggressive behavior and progression in incidental well and moderately differentiated Stage T1a PCa.

P16 Immunoreactivity Is an Independent Predictor of Tumor Progression in Minimally Invasive Urothelial Bladder Carcinoma

Objective: To evaluate the prognostic impact of p16 immunoreactivity in minimally invasive transitional cell bladder carcinomas (stage T1). Methods: Multitissue-arrays containing 73 samples of T1 bladder carcinomas were stained immunohistochemically for p16. Additionally, p53 and Ki-67 antigen expression were examined. A multivariate analysis including other prognostically relevant factors like tumor grade and substage was performed. Results: Loss of p16 expression occurred in 54% of cases and was significantly associated with reduced progression-free ( p = 0.018 by univariate analysis), but not with recurrence-free survival ( p = 0.341). Median Ki-67 antigen and p53 index were 51% (range, 1–93%) and 10% (range, 0–100%), respectively. Both indices correlated significantly ( p = 0.041 and p = 0.024, respectively) with recurrence-free, but not with progression-free survival. Also tumor grade was significantly associated with tumor recurrence ( p = 0.006). By multivariate analysis, tumor grade ( p = 0.008) was identified as an independent predictor of tumor recurrence, whereas p16 expression ( p = 0.009) was identified as an independent predictor of tumor progression. Conclusion: According to our data, there is a significant correlation between loss of p16 expression and tumor progression in patients with minimally-invasive bladder cancer. Immunohistochemical p16 staining may therefore represent a useful tool of providing additional information on the clinical outcome of these patients.

Expression of Platelet-Derived Growth Factor-AA is Associated with Tumor Progression in Osteosarcoma

Platelet-derived growth factors are secreted by mesenchymal cells. The homodimer platelet-derived growth factor-AA especially stimulates bone cells through interaction with the platelet-derived growth factor-α receptor homodimer. In this study we wanted to determine the expression of the receptor and its ligand in human osteosarcomas and to correlate the expression of platelet-derived growth factor-AA and -α receptor with clinicopathological parameters. Fifty-seven osteosarcomas were immunohistochemically analyzed for expression of platelet-derived growth factor-AA and platelet-derived growth factor-α receptor. Spearman's correlation coefficient revealed a strong correlation between the expression of platelet-derived growth factor-AA and platelet-derived growth factor-α receptor (r = 0.867). No differences were observed relative to gender, age, tumor stage, tumor location, and response to neoadjuvant chemotherapy between high or low platelet-derived growth factor-AA and platelet-derived growth factor-α receptor expression. High platelet-derived growth factor-AA expression correlated with tumor progression in univariate analysis (P = .0415; log-rank test), whereas platelet-derived growth factor-α receptor expression showed a trend toward a shorter disease-free survival, which failed to reach significance (P = .0627, log-rank test). In multivariate analysis, platelet-derived growth factor-AA expression remained a significant independent predictor of tumor progression (P = .021, Cox regression). Immunohistochemical analysis of platelet-derived growth factor-AA expression in osteosarcoma may be a useful marker of prognosis and may be considered as a possible target for novel therapeutic strategies.

Predictive value of molecular alterations for the prognosis of urothelial carcinoma.

Accumulation of p53 and C-Myc overexpression are frequently found in advanced urothelial carcinomas. The prevalence and predictive value of both molecular alterations was investigated in 61 patients with superficial urothelial tumors. Distinct patterns of p53 accumulation and C-Myc overexpression were observed in superficial urothelial carcinoma of different stages. For instance, 67% of carcinomata in situ displayed accumulation of p53, but only 44% showed C-Myc overexpression, whereas in pT1 tumors the corresponding percentages were 25 and 75%. Similarly, while p53 accumulation was significantly (p = 0.02) associated with tumor grade, C-Myc overexpression did not correlate with grade. In multivariate analysis, p53 accumulation was found to be an independent predictor of tumor progression (p = 0.0096), whereas C-Myc overexpression did not correlate with the course of disease. Alterations in both markers together predicted neither tumor recurrence nor tumor progression better than p53 accumulation on its own. Sufficient expression of C-Myc may be a general requirement for proliferative competence in urothelial tumors, barring its use as a predictive marker. The predictive value of p53 accumulation for tumor progression was further underlined by the finding that in a distinct group of 52 patients with progressive urothelial carcinoma 73% of the recurrent tumors displayed p53 accumulation.