CINSARC signature as a prognostic marker for clinical outcome in sarcomas and beyond

Background: The identification of highly reliable outcome predictors in severe sepsis is important to define disease severity, predict bedside prognosis and monitor response to treatment. Cell-free plasma DNA (cfDNA) has been recently proposed as a possible prognostic marker of clinical outcome in septic patients. In this study, we investigated the prognostic value of cfDNA in patients with sepsis and its possible correlation with caspase-3, IL-6 and IL-18 levels. Methods: We enrolled 34 patients admitted to the intensive care unit (ICU). Out of these 34, 27 patients were septic and 7 were non-septic. cfDNA was extracted from plasma and quantified by real time PCR. Plasma levels of caspase-3, IL-6 and IL-18 were measured by ELISA. Results: We observed significantly higher levels of cfDNA in septic patients. No significant differences were found between cfDNA levels in patients with Gram+, Gram- and fungal infections. Out of the 27 septic patients, 12 developed acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), and cfDNA levels resulted to be higher in this group. Out of the 27 septic patients, 11 had a negative outcome during the ICU stay. The cfDNA concentrations at admission were higher in non-survivors than in survivors. Caspase-3, IL-6 and IL-18 levels were significantly higher in septic patients when compared to these levels in non-septic patients and correlated with cfDNA levels. Conclusion: cfDNA can be considered a good prognostic marker of clinical outcome in septic patients. Its levels increase in case of AKI complicating sepsis, in particular if CRRT is needed, and are associated with poor outcome. Caspase-3, IL-6 and IL-18 levels are higher in septic patients and correlate to cfDNA concentrations.

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PROGNOSTIC SIGNIFICANCE OF MDM2 GENE EXPRESSION IN CHILDHOOD NEUROBLASTOMA

Experimental Oncology ◽

10.31768/2312-8852.2015.37(2):111-115 ◽

2015 ◽

Vol 37 (2) ◽

pp. 111-115 ◽

Cited By ~ 8

Author(s):

M V Inomistova ◽

N M Svergun ◽

N M Khranovska ◽

O V Skachkova ◽

O I Gorbach ◽

...

Keyword(s):

Clinical Outcome ◽

Prognostic Marker ◽

Gene Deletion ◽

Tp53 Gene ◽

Mycn Amplification ◽

Mrna Levels ◽

Event Free Survival ◽

Free Survival ◽

Mdm2 Expression ◽

Mdm2 Mrna

Aim: To investigate the association of MDM2 expression at the mRNA levels in neuroblastoma with clinical features and unfavorable disease factors to determine the possibility of it usage as a prognostic marker of neuroblastoma. Materials and Methods: Total RNA and DNA were extracted from tumor tissue samples of total 91 neuroblastoma patients (mean age: 39.45 ± 4.81 months). MDM2 mRNA levels were detected with Q-PCR. TP53 gene deletion was detected with FISH method. MYCN amplification was detected with Q -PCR analysis in fresh tumor samples and FISH in FFPE samples. Results: We investigated the association of MDM2 mRNA expression with clinical outcome in neuroblastoma patients (n = 91). Kaplan — Meier curves showed a significant association of high MDM2 expression with poor event-free survival (p < 0.001). Clinical outcome of patients without MYCN amplification with low MDM2 expression was associated with better event-free survival than with high MDM2 expression (p < 0.001). Overexpression of MDM2 can be used as significant prognostic marker for patient stratification on risk groups and treatment optimization. Conclusion: Our results showed that the high expression of MDM2 at mRNA levels is an important factor of neuroblastoma prognosis. It may be a valuable additional molecular marker in guiding specific therapy in MYCN non-amplified NB patients without TP53 gene deletion.

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Minichromosome maintenance protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients

Acta Endocrinologica ◽

10.1530/eje-15-0586 ◽

2016 ◽

Vol 174 (3) ◽

pp. 307-314 ◽

Cited By ~ 7

Author(s):

Antonella Coli ◽

Sylvia L Asa ◽

Guido Fadda ◽

Domenico Scannone ◽

Sabrina Chiloiro ◽

...

Keyword(s):

Pituitary Adenoma ◽

Clinical Outcome ◽

Prognostic Marker ◽

Progression Free Survival ◽

Tumor Aggressiveness ◽

Minichromosome Maintenance ◽

Ki 67 ◽

Free Survival ◽

Risk Of Recurrence ◽

Nuclear Expression

BackgroundKi-67 labeling index (LI) is currently regarded as a useful prognostic marker of pituitary adenoma (PA) clinical behavior, although its relevance as a reliable clinical indicator is far from being universally accepted, since both validations and criticisms are found in the literature. Minichromosome maintenance 7 (MCM7), a cell-cycle regulator protein, has been recently proposed as a marker of tumor aggressiveness in tumors from many sites, including the CNS. Therefore, we evaluated MCM7, in comparison to Ki-67, as a potential marker of clinical outcome in PA.Design and methodsIn this single-institution retrospective study, 97 patients with PA (23 ACTH, 12 GH, 29 PRL, 10 FSH/LH, and 23 non-secreting adenomas) were recruited and the prognostic value of both MCM7 and Ki-67 was evaluated by immunohistochemical techniques. In addition, p53 nuclear expression and mitotic index were also evaluated.ResultsTwenty-six of the 97 PA patients recurred during the follow-up period. Cox's regression analysis showed that high nuclear expression of MCM7 LI, unlike Ki-67 LI, was directly associated with a higher (7.7-fold) risk of recurrence/progression. Kaplan–Meier analysis of recurrence/progression-free survival curves revealed that patients with high MCM7 LI (≥15%) had a shorter recurrence/progression-free survival than those with low MCM7 LI (<15%). Moreover, among patients with invasive tumors, high MCM7 LI identified those with the highest risk of recurrence/progression.ConclusionsData from this study suggest that MCM7 is a prognostic marker of clinical outcome in PA patients, more reliable and informative than Ki-67.

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Immunohistochemical Prognostic Marker for Diffuse Large B Cell Lymphoma in Patients Treated with CHOP Like Chemotherapy: Validation of the Algorithm by Hans Et Al. and Analysis of Individual Markers

Blood ◽

10.1182/blood.v112.11.5274.5274 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5274-5274

Author(s):

Cheolwon Suh ◽

Jooryung Huh ◽

Sukjoong Oh ◽

Jeong-Hyeon Jo ◽

Shin Kim ◽

...

Keyword(s):

Clinical Outcome ◽

B Cell ◽

Clinical Significance ◽

Prognostic Marker ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cut Point ◽

Independent Prognostic Marker ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background) Recently, many predictive models of the clinical outcome of diffuse large B cell lymphoma (DLBCL) have been proposed for better stratification of subgroups. However, studies of the protein expression have reported conflicting results, predominantly due to the lack of universally accepted cut-off value for positivity. Here we retrospectively analyzed the expression of CD10, BCL6, MUM1, BCL2, and CD5 in Korean DLBCL patients treated with CHOP like regimen using the widely used algorithm by Hans et al. (Blood 2004) and compared the results with different cut-off values. We also investigated the clinical significance of individual biomarkers. Methods) Of the DLBCL cases retrieved from the file of Pathology, Asan medical center (1999–2004). Ninety four (94) cases with adequate tissue were included. Clinical characteristics, treatment and outcome of these patients were collected from the AMC data base. Immunohistochemical stains were performed on tissue microarray (TMA) sections of the archival material. According to Hans’ algorithm, cases were divided into germinal center B-cell like (GCB) (either CD10+ or BCL6+MUM1−)(19.1%) and activated B cell-like (ABC) (CD10−BCL6− or BCL6+MUM1+), with a universal cut-off value of 30% or more of the positively-stained tumor cells. The percentage of the positivity was also recorded in each case. The four cutpoints (0%, 1–30%, 31–50%, 51–75%, and 76–100%) were investigated for each marker for best correlation with the clinical outcome. Results) During the 5-year median follow up, median overall survival was not reached. Hans’ algorithm divided the cases into 18 GCB (19.1%) and 76 ABC tumors (80.9%), with no clinical significance (3-year PFS: GCB group 63%, ABC group 62%). Among individual biomarkers, CD5− group (cut point: any positivity), bcl-6+ group (cut point: any positivity) and CD10+ group (cut point: 30%) had longer PFS, and bcl-6+ group (cut point: any positivity) had longer OS in univariate analysis. Multivariate Cox regression analysis showed CD10 (p=0.003) as independent prognostic marker in PFS; and bcl-6 (p=0.03) as independent prognostic marker in OS. Conclusion) The present study shows the lack of predictability of Hans’ algorithm in DLBCL patients treated with CHOP like regimen among Koreans, while CD10, Bcl-6, and CD5 had the prognostic significance using different cut-off values. The result suggests that the proposed cut-off value may not be applied universally for best correlation, and that the optimal cut-off value may need to be optimized for individual laboratory.

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Engraftment of resected pancreatic adenocarcinoma in SCID mice and patient survival following surgical resection: Roswell Park's experience.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.185 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 185-185

Author(s):

Jose Luis Aranez ◽

Potjana Jitawatanarat ◽

Bonnie Hylander ◽

Rose Pitoniak ◽

Charles Levea ◽

...

Keyword(s):

Pancreatic Cancer ◽

Clinical Outcome ◽

Pancreatic Adenocarcinoma ◽

Prognostic Marker ◽

Statistical Significance ◽

Scid Mice ◽

Resectable Pancreatic Cancer ◽

Baseline Information ◽

Potential Link ◽

Index Value

185 Background: Preclinical models developed by implanting resected pancreatic cancer from human donors into immunocompromised (SCID) mice have been valuable in understanding the disease’s biology and developing therapies. The ability of resected tumors to engraft successfully has previously been reported to be a poor prognostic marker. This study was conducted to investigate the relationship between successful engraftment and clinical outcome by analyzing such a model developed at Roswell Park over the last decade. Methods: A retrospective review of 48 donor patients (27 males and 21 females) whose resected pancreatic adenocarcinoma was xenografted in SCID mice between 1999-2009 was conducted. The clinical outcome and baseline information were correlated with engraftment outcome. The expression of potential biomarkers correlating with engraftment was evaluated by performing immunohistochemistry on the initial donor surgical specimens. The expression was scored, assigned an average index value and categorized into groups (High vs Low expression) based on a median cutoff of values. Results: Resected tumors from 21 of the 48 donors successfully engrafted when implanted subcutaneously in SCID mice (44%). The baseline demographics and disease characteristics were balanced between engrafters versus non-engrafters. All of the engrafters and 26 (of 27) of non-engrafters received adjuvant treatment. The 2-year overall survival (OS) of patients whose tumors successfully engrafted was 17% compared to 39% in those whose tumors failed to engraft (P=0.09; hazard ratio 1.305 [95% CI 0.717-2.375]). Analysis to identify potential biological markers associated with engraftment success is underway. Conclusions: A review of the clinical outcome of patients whose tumors were procured and used for the patient-derived primary pancreatic cancer xenograft program at Roswell Park showed that successful engraftment in SCID mice is potentially a poor prognostic marker in patients with resectable pancreatic cancer. Our analysis did not reach statistical significance which is likely due to a smaller sample size but the potential link is consistent with that reported by others.

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