Faculty Opinions recommendation of BCL-2/IgH polymerase chain reaction status at the end of induction treatment is not predictive for progression-free survival in relapsed/resistant follicular lymphoma: results of a prospective randomized EORTC 20981 phase III intergroup study.

Purpose The prognostic value of residual BCL2/immunoglobulin heavy chain (BCL2/IgH) –positive cells in peripheral blood (PB) or bone marrow (BM) after induction treatment in follicular lymphoma (FL) is still controversial. In a prospective randomized phase III intergroup trial of 465 patients with relapsed/resistant follicular lymphoma (FL), we showed that addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone induction results in increased overall and complete response rates, and that rituximab maintenance strongly improves median progression-free survival (PFS) as well as overall survival. Here, we studied whether BCL2/IgH major break point levels in PB/BM correlated with response rates/quality for the induction phase and PFS for the maintenance phase. Patients and Methods Samples were obtained before and after induction therapy and at the end of the 2 years maintenance/observation period. BCL2/IgH major break point–positive cells were quantified by genomic quantitative polymerase chain reaction in 792 samples from 238 patients. Results Pretreatment BCL2/IgH levels had no significant prognostic value for overall response or complete remission rates after induction treatment, but pretreatment positive BM results had an adverse prognostic value for PFS from first randomization (P = .023). Importantly, BCL2/IgH levels at the end of induction treatment had no prognostic value for PFS from second randomization. The highly significant improved PFS by rituximab maintenance was observed in both BCL2/IgH PB/BM–positive and –negative groups. Conclusion Postinduction BCL2/IgH major break point status in BM/PB is not useful for decisions on subsequent therapy for patients with relapsed/resistant FL.

Download Full-text

Quantitative PCR Analysis for Bcl-2/IgH in a Phase III Study of Yttrium-90 Ibritumomab Tiuxetan As Consolidation of First Remission in Patients With Follicular Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.22.6258 ◽

2009 ◽

Vol 27 (36) ◽

pp. 6094-6100 ◽

Cited By ~ 31

Author(s):

Lindsey Goff ◽

Karin Summers ◽

Sameena Iqbal ◽

Jens Kuhlmann ◽

Michael Kunz ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Follicular Lymphoma ◽

Quantitative Polymerase Chain Reaction ◽

Phase Iii ◽

Pcr Analysis ◽

Control Group ◽

Ibritumomab Tiuxetan ◽

Chain Reaction ◽

Polymerase Chain ◽

Yttrium 90

Purpose The randomized First-Line Indolent Trial (FIT) was conducted in patients with advanced follicular lymphoma (FL), to evaluate the safety and efficacy of yttrium-90 (90Y) ibritumomab tiuxetan given as consolidation of complete or partial remission. This study of minimal residual disease was undertaken in parallel, to determine the rate of conversion from bcl-2 polymerase chain reaction (PCR) –detectable to –undetectable status and the corresponding effect on progression-free survival (PFS). Patients and Methods Blood samples from 414 patients (90Y-ibritumomab, n = 208; control, n = 206) were evaluated using real-time quantitative polymerase chain reaction (RQ-PCR); 186 were found to have the bcl-2 rearrangement and were thus eligible for inclusion in the RQ-PCR analysis. Results Overall, 90% of treated patients converted from bcl-2 PCR–detectable to –undetectable disease status, compared with 36% in the control group. Treatment significantly prolonged median PFS in patients converting to bcl-2 PCR-undetectable status (40.8 v 24.0 months in the control group; P < .01, hazard ratio [HR], 0.399). In patients who had bcl-2 PCR-detectable disease at random assignment, treatment significantly prolonged median PFS (38.4 v 8.2 months in the control group; P < .01, HR, 0.293). Conclusion Eradication of PCR-detectable disease occurred more frequently after treatment with 90Y-ibritumomab tiuxetan and was associated with prolongation of PFS.

Download Full-text

Long non-coding RNA TIRY promotes tumor metastasis by enhancing epithelial-to-mesenchymal transition in oral cancer

Experimental Biology and Medicine ◽

10.1177/1535370220903673 ◽

2020 ◽

Vol 245 (7) ◽

pp. 585-596 ◽

Cited By ~ 4

Author(s):

Nuo Jin ◽

Nianqiang Jin ◽

Wenhuan Bu ◽

Xing Li ◽

Lili Liu ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Epithelial To Mesenchymal Transition ◽

Tumor Biology ◽

Progression Free Survival ◽

Cancer Associated Fibroblasts ◽

Chain Reaction ◽

Free Survival ◽

Mesenchymal Transition ◽

Polymerase Chain

Long non-coding RNAs (lncRNAs) modulate a variety of cancerous biological processes, including the promotion of tumorigenicity in tumor parenchymal cells. However, there is a lack of studies assessing the regulation of lncRNAs in cancer-associated fibroblasts. In the present study, a novel lncRNA, TIRY, was found to act as a miRNA sponge and to downregulate miR-14 expression in oral squamous cell carcinoma (OSCC). Fluorescence in situ hybridization assay was used to evaluate TIRY expression in OSCC tissues. Survival analysis in a prospective cohort revealed a correlation between high TIRY expression and short progression-free survival. Subsequently, TIRY expression in cancer-associated fibroblasts and primary fibroblasts from adjacent normal (para-carcinoma) tissues was assessed using quantitative reverse transcription polymerase chain reaction. TIRY overexpression in cancer-associated fibroblasts isolated from OSCC tissues was induced by overexpressing the TIRY plasmid, and candidate microRNA expressions were assessed using quantitative real-time polymerase chain reaction. Moreover, the expression of proteins related to epithelial-to-mesenchymal transition (EMT) was determined; the proliferation, metastasis, and invasion of cancer cells co-cultured with TIRY-overexpressing cancer-associated fibroblasts were determined. We found significantly decreased miR-14 expression in cancer-associated fibroblast-derived exosomes and increased expression of EMT markers including transcription factors (Snail and FOXC2) and cellular scaffolding proteins (α-SMA, β-catenin, and FSP1). TIRY overexpression in cancer-associated fibroblasts activated the Wnt/β-catenin signaling pathway and promoted the invasion and metastasis of OSCC cells through miR-14 sponging based on cancer-associated exosome secretion. Our findings provide a novel molecular mechanism underlying the role of TIRY in cancer-associated fibroblasts in tumor biology; moreover, TIRY is a potential therapeutic target in OSCC. Impact statement This study demonstrated the novel lncRNA, TIRY, enhances epithelial-to-mesenchymal transition in cancer-associated fibroblasts and promotes the metastasis of tumor via miR-14 sponging in oral squamous cell carcinoma, and thus provide a novel molecular mechanism underlying the role of TIRY in CAFs in tumor biology and a potential target in OSCC. Further, the data showed that TIRY expression was negatively correlated with miR-14 transcription levels and was associated with poor prognosis in OSCC specimens. Therefore, TIRY may be a potential prognostic biomarker of overall survival and progression-free survival in OSCC. Moreover, TIRY adds to the understanding of regulatory mechanisms involved in CAFs and epithelial cancer cells in OSCC and may provide novel insights for further understanding tumor biology.

Download Full-text

BCL-2/IgH PCR Values at the End of Induction Treatment Are Not Predictive for Progression Free Survival in Relapsed/Resistant Follicular Lymphoma: Results of a Prospective Randomized Phase III Intergroup Trial.

Blood ◽

10.1182/blood.v110.11.791.791 ◽

2007 ◽

Vol 110 (11) ◽

pp. 791-791

Author(s):

Bert A. van der Reijden ◽

Marinus H.J Van Oers ◽

Evelyn Tonissen ◽

Martine Van Glabbeke ◽

Livia Giurgia ◽

...

Keyword(s):

Follicular Lymphoma ◽

Induction Therapy ◽

Progression Free Survival ◽

Phase Iii ◽

Remission Induction ◽

Induction Treatment ◽

Induction Phase ◽

Main Question ◽

Free Survival ◽

Intergroup Trial

Abstract Background. The predictive value of assessment of minimal residual disease after induction treatment in follicular lymphoma (FL) is still controversial. Last year we published the results of a prospective randomized phase III intergroup trial evaluating the role of rituximab (R) both in remission induction and maintenance treatment of 465 relapsed /resistant FL patients. Major conclusions were that addition of R to CHOP induction yielded an increased ORR and CR rate, and that R maintenance strongly improved median progression free survival (PFS; both after induction with CHOP and R-CHOP) and overall survival when compared to observation (van Oers et al Blood2006;108:3295). We now report on the Bcl-2/IgH PCR analysis in this study. Study design. Peripheral blood (PB) and bone marrow (BM) samples where obtained before the start of the induction therapy, at the end of the induction therapy and at the end of the 2 years maintenance/ observation period. The percentage of Bcl-2/IgH MBR+ cells was quantified by genomic qPCR with a sensitivity of at least one Bcl-2/IgH MBR+ cell among 10,000 normal cells (primer and probe sequences are available on request. The main question of our analysis was whether the primary endpoints of the study (response rate /quality for the induction phase and PFS for the maintenance phase) were correlated with results of the Bcl-2/IgH PCR in PB or BM. Results. Molecular biology data were available from 250 patients, evenly distributed amongst the therapeutic arms, both for induction and maintenance. Before treatment 48.5% and 42.0% of assessable patients had a positive Bcl-2/IgH PCR in BM and PB respectively. At the end of induction this had decreased to 28.6% and 17.3% respectively, and at the end of maintenance/observation to 10.5% and 10.6%. Conversion of positive to negative values were more frequent with R-CHOP induction (BM: P=0.026 and PB: P=0.003), and with R maintenance (BM: P=0.005). Percentages and levels of Bcl-2/IgH positivity in PB and BM correlated well at the three sampling time points. Bcl-2/IgH PCR results at diagnosis did not predict for overall response or complete remission rates after induction treatment, but BM results predicted PFS (P=0.04). Rather surprisingly, Bcl-2/IgH PCR results of BM and PB at the end of induction treatment were not predictive for PFS: 3 years PFS was 46% and 38% in the BM− and BM+ group respectively (p=0.4), and 51% and 42% in the PB-and PB+ group respectively (p=0.4).The highly significant improvement of PFS by R maintenance versus observation was observed in both Bcl-2/IgH PCR PB/BM positive and negative groups. Finally, patients who still had a positive Bcl-2/IgH PCR in PB or BM at the end of the 2 years of R maintenance/observation had a significantly shorter PFS (from end of maintenance/observation) than those who were Bcl-2/IgH PCR negative. Conclusion: Bcl-2/IgH PCR results in BM or PB at the end of CHOP or R-CHOP induction treatment are not useful for decisions on subsequent therapy in patients with relapsed/resistant follicular lymphoma.

Download Full-text

Detection of BCL-2 Gene Rearrangement in Follicular Lymphoma by Polymerase Chain Reaction and Chemiluminescence Technique

Annals of Saudi Medicine ◽

10.5144/0256-4947.1997.423 ◽

1997 ◽

Vol 17 (4) ◽

pp. 423-426

Author(s):

Salem H. Khalil ◽

Karen Siegrist ◽

M. Ashraf Ali

Keyword(s):

Polymerase Chain Reaction ◽

Follicular Lymphoma ◽

Gene Rearrangement ◽

Chain Reaction ◽

Polymerase Chain

Download Full-text

Maintenance Rituximab After Cyclophosphamide, Vincristine, and Prednisone Prolongs Progression-Free Survival in Advanced Indolent Lymphoma: Results of the Randomized Phase III ECOG1496 Study

Journal of Clinical Oncology ◽

10.1200/jco.2008.17.1561 ◽

2009 ◽

Vol 27 (10) ◽

pp. 1607-1614 ◽

Cited By ~ 202

Author(s):

Howard Hochster ◽

Edie Weller ◽

Randy D. Gascoyne ◽

Thomas M. Habermann ◽

Leo I. Gordon ◽

...

Keyword(s):

Follicular Lymphoma ◽

Residual Disease ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

Tumor Burden ◽

Phase Iii ◽

Indolent Lymphoma ◽

Free Survival ◽

Rank One

Purpose To determine if maintenance rituximab (MR) after standard chemotherapy improves progression-free survival (PFS) in advanced-stage indolent lymphoma. Patients and Methods Patients with stage III-IV indolent lymphoma with responding or stable disease after cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy were stratified by initial tumor burden, residual disease after CVP (minimal or gross), and histology, and randomly assigned to observation (OBS) or MR 375 mg/m2 once per week for 4 weeks every 6 months for 2 years. PFS was the primary end point. Results Three hundred eleven (282 with follicular lymphoma) evaluable patients who received CVP were randomly assigned to OBS (n = 158) or MR (n = 153). Best response improved in 22% MR versus 7% OBS patients (P = .00006). Toxicity was minimal in both study arms. Three-year PFS after random assignment was 68% MR versus 33% OBS (hazard ratio [HR] = 0.4; P = 4.4 × 10−10 [all patients]) and 64% MR v 33% OBS (HR = 0.4; P = 9.2 × 10−8 [patients with follicular lymphoma]). There was an advantage for MR regardless of Follicular Lymphoma International Prognostic Index score, tumor burden, residual disease, or histology. In multivariate analysis of MR patients, minimal disease after CVP was a favorable prognostic factor. OS at 3 years was 92% MR versus 86% OBS (HR = 0.6; log-rank one-sided P = .05) and, among patients with follicular lymphoma, OS was 91% MR versus 86% (HR = 0.6; log-rank one-sided P = .08). A trend favoring MR was observed among patients with high tumor burden (log-rank one-sided P = .03). Conclusion The E1496 study provides the first phase III data in untreated indolent lymphoma that MR after chemotherapy significantly prolongs PFS.

Download Full-text

Prognostic role of EZH2 in gliomas: a meta-analysis

The International Journal of Biological Markers ◽

10.5301/ijbm.5000293 ◽

2017 ◽

Vol 33 (1) ◽

pp. 62-67 ◽

Cited By ~ 6

Author(s):

Jung-Soo Pyo ◽

Dong-Wook Kang

Keyword(s):

Polymerase Chain Reaction ◽

Meta Analysis ◽

Progression Free Survival ◽

Tumor Grade ◽

Detection Methods ◽

Prognostic Role ◽

Chain Reaction ◽

Ezh2 Expression ◽

Positive Rate ◽

Polymerase Chain

Background: The aim of this study was to elucidate the clinicopathological significance of enhancer of zeste homolog 2 (EZH2) expression in gliomas, including its incidence and prognostic role. In addition, we investigated the concordance between immunohistochemistry and polymerase chain reaction for determining the presence or absence of EZH2 in these tumors. Methods: The current meta-analysis included 1,049 gliomas with various WHO tumor grades from 12 eligible studies, which were analyzed for positivity of EZH2 and correlation between EZH2 expression and prognosis. Subgroup analyses were performed based on detection methods and WHO tumor grades. Results: We found the estimated positive rate of EZH2 in gliomas to be 0.663 (95% confidence interval [95% CI], 0.549-0.761). There was no difference between immunohistochemistry and polymerase chain reaction in determination of EZH2 positivity (0.706, 95% CI, 0.539-0.831 vs. 0.673, 95% CI, 0.472-0.825). The positive rate of EZH2 increased by increasing WHO tumor grade. EZH2 expression was significantly correlated with worse overall and progression-free survival (hazard ratio [HR] = 2.436, 95% CI, 1.350-4.393, and HR = 4.071, 95% CI, 1.325-12.508, respectively). The overall concordance rate between immunohistochemistry and polymerase chain reaction was 0.885 (95% CI, 0.300-0.993). Conclusions: EZH2 positivity was significantly correlated with WHO tumor grade and worse prognosis in gliomas.

Download Full-text