The Experts below are selected from a list of 9495 Experts worldwide ranked by ideXlab platform
Clara D Bloomfield - One of the best experts on this subject based on the ideXlab platform.
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quantification of cbfβ myh11 Fusion Transcript by real time rt pcr in patients with inv 16 acute myeloid leukemia
Leukemia, 2001Co-Authors: Guido Marcucci, Michael A Caligiuri, Hartmut Dohner, Kellie J Archer, Richard F Schlenk, Konstanze Dohner, E A Maghraby, Clara D BloomfieldAbstract:Quantification of CBFβ/MYH11 Fusion Transcript by Real Time RT-PCR in patients with INV(16) acute myeloid leukemia
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detection of minimal residual disease in patients with aml1 eto associated acute myeloid leukemia using a novel quantitative reverse Transcription polymerase chain reaction assay
Leukemia, 1998Co-Authors: G Marcucci, Clara D Bloomfield, Kenneth J Livak, Matthew P Strout, Michael A CaligiuriAbstract:The AML1/ETO Fusion Transcript can be detected by reverse Transcription polymerase chain reaction (RT-PCR) in patients with t(8;21)-associated acute myeloid leukemia (AML) in long-term complete remission (CR). Quantitation of the amount of the Fusion Transcript during CR may therefore be more predictive of cure or relapse than a simple qualitative assessment. Real Time PCR, a fluorometric-based technique, allows simple and rapid quantitation of a target sequence during the extension phase of PCR amplification, in contrast to end-point quantitative methods. Six patients with t(8;21)(q22;q22) AML, who achieved CR were studied by Real Time RT-PCR at different time intervals following diagnosis and high-dose cytarabine and anthracycline-based induction therapy. Five patients had a diagnostic bone marrow (BM) sample available for molecular analysis. Each patient showed ⩾103 copies of the AML1/ETO Fusion Transcript at diagnosis, and each showed a 2- to 4-log decrease in copy number following successful induction chemotherapy. This is comparable to the log-fold reduction in leukemic blasts that is thought to occur in patients successfully cytoreduced into CR by induction chemotherapy. The sixth patient showed a relatively high copy number immediately following successful remission induction chemotherapy, which continued to increase during early CR and was later followed by relapse. Real Time RT-PCR appears to offer advantages over previously used quantitative RT-PCR methods by providing absolute quantitation of the target sequence, expanding the dynamic range of quantitation to over six orders of magnitude, eliminating the post-PCR processing, and reducing labor and carryover contamination. These features make this an attractive method to prospectively evaluate the prognostic value of AML1/ETO Fusion Transcript quantitation in a larger patient population with t(8;21)(q22;q22) AML in CR.
Peter Hokland - One of the best experts on this subject based on the ideXlab platform.
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persistent altered Fusion Transcript splicing identifies runx1 runx1t1 aml patients likely to relapse
European Journal of Haematology, 2010Co-Authors: Hans Beier Ommen, Karin Braendstrup, Donger Zhang, M Ostergaard, Peter HoklandAbstract:Abstract In acute myeloid leukemia (AML) mouse models, the RUNX1-RUNX1T1 Fusion protein has failed to produce leukemia by itself, but alternative splicing of exon 9a of the RUNX1-RUNX1T1 Fusion Transcript (FT) has recently been shown to enhance the leukemogenic potential. We have analyzed 138 diagnosis and follow-up samples from 13 RUNX1-RUNX1T1+ patients as well as diagnosis samples from 13 RUNX1-RUNX1T1- AML patients and 26 healthy donors. Levels of native RUNX1T1 mRNA were low in both healthy and RUNX1-RUNX1T1-negative AML samples. Likewise, the ratio between RUNX1T1 mRNA harboring exon 9a and lacking exon 9a was low and tightly regulated (0.017-0.11). In contrast, 11/13 RUNX1-RUNX1T1-positive AML patients displayed high and variable ratios of FT ranging from 0.05 to 0.46 (P < 0.001, Wilcoxon rank-sum test), indicating altered exon 9a splicing in these patients. Importantly, patients who remained in continuous complete remission displayed a faster disappearance of the RUNX1-RUNX1T1 exon 9a splice variant compared to patients bound to relapse (P = 0.02). In conclusion, alternative splicing seems to be part of the leukemogenic process in the majority of RUNX1-RUNX1T1-positive AML patients, and splice variant kinetics under cytoreduction may be a predictor for patients prone to relapse.
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wt1 gene expression an excellent tool for monitoring minimal residual disease in 70 of acute myeloid leukaemia patients results from a single centre study
British Journal of Haematology, 2004Co-Authors: M Ostergaard, Eigil Kjeldsen, Lene Hyldahl Olesen, Henrik Hasle, Peter HoklandAbstract:Summary Following induction chemotherapy for acute myeloid leukaemia (AML), sensitive determination of minimal residual disease (MRD) in patients achieving complete remission (CR) should enable the detection of early relapse and allow intervention at a more favourable stage than at overt relapse. We have determined the expression levels of the Wilms’ tumour gene (WT1) by real-time quantitative polymerase chain reaction (RQ-PCR) in peripheral blood and bone marrow in 133 newly diagnosed AML patients and compared them with those in healthy volunteers. At diagnosis, the WT1 level exceeded normal expression in 118 of 133 (89%) patients, and was high enough to allow for detection of a WT1 decrease of least 1000-fold in 98 of 133 (74%) patients following induction therapy. Concomitant monitoring of Fusion Transcripts (PML-RARα, AML1-ETO, MLL-MLL, CBFβ-MYH11, or DEK-CAN) in 38 patients identified different relationships between WT1 and Fusion Transcript levels, the AML1-ETO group showing remarkably low levels of WT1 compared with Fusion Transcript. In 32 patients analysed longitudinally there was close concordance between relapse and increased WT1 levels. Parallel longitudinal monitoring of WT1 and Fusion Transcript showed close correlation in 18 of 18 patients. We conclude that WT1 expression by RQ-PCR may be employed as a tool to detect MRD in the majority of Fusion Transcript-negative AML patients.
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kinetics of bcr abl Fusion Transcript levels in chronic myeloid leukemia patients treated with sti571 measured by quantitative real time polymerase chain reaction
European Journal of Haematology, 2001Co-Authors: Jesper Stentoft, Niels Pallisgaard, Eigil Kjeldsen, Mette Skov Holm, Johan Lanng Nielsen, Peter HoklandAbstract:Abstract: The activated tyrosine kinase, which arises as a result of the balanced t(9,22) translocation in chronic myeloid leukemia (CML), is thought to be essential for the development of the leukemic phenotype. Recently, designer drugs have been introduced which specifically inhibit such specific kinases. Among these, STI571 (GlivecTM) has entered clinical trials and shown promising activities in chronic phase (CP), accelerated phase (AP) and blast crisis (BC) as evidenced by significant hematological and cytogenetic responses in CML patients. To evaluate the effect of STI571 at the molecular level we have employed quantitative real-time PCR (RQ-PCR) to measure the amount of BCR-ABL Fusion Transcript in a series of 19 patients treated with STI571, either in CP(11) or in (AP)(8) of the disease for 3–9 months (median 6 months). Employing this method, which is able to detect at least one BCR-ABL+ cell in 500 000, in serial blood and bone marrow specimens we found decreases in Transcript levels in 10/11 CP patients, but only in 1/8 of the AP patients. When present such decreases were gradual and became evident only after 3 months of STI571 treatment, and their kinetics in blood closely mirrored those seen in parallel marrow samples. Moreover, decreases were between 10- and 100-fold in 11/13 patients, with only two patients reaching residual disease levels below 10−2 (a 900-fold decrease). Thus, no patient reached PCR negativity. We conclude that the RQ-PCR method is a highly suitable tool for following the effect of STI571 in CML and that further validation of the method, performed in a prospective manner, will contribute significantly to the elucidation of the proper role of STI571 in CML.
Michael A Caligiuri - One of the best experts on this subject based on the ideXlab platform.
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quantification of cbfβ myh11 Fusion Transcript by real time rt pcr in patients with inv 16 acute myeloid leukemia
Leukemia, 2001Co-Authors: Guido Marcucci, Michael A Caligiuri, Hartmut Dohner, Kellie J Archer, Richard F Schlenk, Konstanze Dohner, E A Maghraby, Clara D BloomfieldAbstract:Quantification of CBFβ/MYH11 Fusion Transcript by Real Time RT-PCR in patients with INV(16) acute myeloid leukemia
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detection of minimal residual disease in patients with aml1 eto associated acute myeloid leukemia using a novel quantitative reverse Transcription polymerase chain reaction assay
Leukemia, 1998Co-Authors: G Marcucci, Clara D Bloomfield, Kenneth J Livak, Matthew P Strout, Michael A CaligiuriAbstract:The AML1/ETO Fusion Transcript can be detected by reverse Transcription polymerase chain reaction (RT-PCR) in patients with t(8;21)-associated acute myeloid leukemia (AML) in long-term complete remission (CR). Quantitation of the amount of the Fusion Transcript during CR may therefore be more predictive of cure or relapse than a simple qualitative assessment. Real Time PCR, a fluorometric-based technique, allows simple and rapid quantitation of a target sequence during the extension phase of PCR amplification, in contrast to end-point quantitative methods. Six patients with t(8;21)(q22;q22) AML, who achieved CR were studied by Real Time RT-PCR at different time intervals following diagnosis and high-dose cytarabine and anthracycline-based induction therapy. Five patients had a diagnostic bone marrow (BM) sample available for molecular analysis. Each patient showed ⩾103 copies of the AML1/ETO Fusion Transcript at diagnosis, and each showed a 2- to 4-log decrease in copy number following successful induction chemotherapy. This is comparable to the log-fold reduction in leukemic blasts that is thought to occur in patients successfully cytoreduced into CR by induction chemotherapy. The sixth patient showed a relatively high copy number immediately following successful remission induction chemotherapy, which continued to increase during early CR and was later followed by relapse. Real Time RT-PCR appears to offer advantages over previously used quantitative RT-PCR methods by providing absolute quantitation of the target sequence, expanding the dynamic range of quantitation to over six orders of magnitude, eliminating the post-PCR processing, and reducing labor and carryover contamination. These features make this an attractive method to prospectively evaluate the prognostic value of AML1/ETO Fusion Transcript quantitation in a larger patient population with t(8;21)(q22;q22) AML in CR.
Kazuo Shimozato - One of the best experts on this subject based on the ideXlab platform.
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mammary analogue secretory carcinoma of salivary glands a clinicopathologic and molecular study including 2 cases harboring etv6 x Fusion
The American Journal of Surgical Pathology, 2015Co-Authors: Yohei Ito, Satoru Miyabe, Kenichiro Ishibashi, Ayako Masaki, Kana Fujii, Yukio Fujiyoshi, Hideo Hattori, Daisuke Kawakita, Manabu Matsumoto, Kazuo ShimozatoAbstract:Mammary analogue secretory carcinoma (MASC) is a recently described low-grade carcinoma with morphologic and genetic similarity, including ETV6-NTRK3 Fusion, to secretory carcinoma of the breast. ETV6 is frequently involved in other epithelial and nonepithelial tumors, and many Fusion partners of ETV6 have been reported. In the present study, 14 Japanese MASC cases were clinicopathologically and molecularly analyzed. The median age of the patients was 39 years, and the male:female ratio was 6:8. All cases showed histopathologic findings compatible with those previously described for MASC and harbored an ETV6 split as visualized by fluorescence in situ hybridization. Two cases showed thick fibrous septa and invasive features including vascular or perineural tumor involvement, findings that are rare in MASC. In addition, in these 2 cases, non-NTRK3 genes appeared to fuse with ETV6 (ETV6-X Fusion). NTRK1 and NTRK2, both members of the NTRK family, were not involved. Of the 14 MASC cases, the ETV6-NTRK3 Fusion Transcript was positive in 6 cases, and the relative expression level of the ETV6-NTRK3 Fusion Transcript was variable, ranging from 1 to 5.8. Results of the present study of MASC suggest that (1) ETV6 occasionally fuses with unknown non-NTRK3 genes, (2) ETV6-X cases might have an invasive histology, (3) for molecular diagnosis of MASC, fluorescence in situ hybridization to detect ETV6 splits is the method of choice, and (4) the expression level of the ETV6-NTRK3 Fusion Transcript is considerably variable. These findings provide a novel insight into the oncogenesis, histopathology, diagnosis, treatment, and prognosis of this newly recognized carcinoma.
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clinicopathological significance of the crtc3 maml2 Fusion Transcript in mucoepidermoid carcinoma
Modern Pathology, 2009Co-Authors: Takahisa Nakayama, Satoru Miyabe, Mitsukuni Okabe, Kei Ijichi, Hitoshi Nagatsuka, Yasuhisa Hasegawa, Hidenori Sakuma, Kazuo ShimozatoAbstract:Mucoepidermoid carcinoma is the most common primary malignancy of the salivary gland. We and others showed that CRTC1-MAML2 gene Fusion was associated with favorable clinicopathological tumor features. Recently, a novel gene Fusion, CRTC3-MAML2, was reported as a rare gene alteration in a case of mucoepidermoid carcinoma. However, its frequency and clinicopathological significance remains unclear. In all, 101 cases of mucoepidermoid carcinoma and 89 cases of non-mucoepidermoid carcinoma of the salivary gland were analyzed, and RNA was extracted from formalin-fixed, paraffin-embedded specimens. In the CRTC family, there have been three genes, CRTC1, CRTC2, and CRTC3. We developed reverse Transcription-polymerase chain reaction (RT-PCR) assays for CRTC1-MAML2, CRTC2-MAML2, and CRTC3-MAML2 Fusions. Clinicopathological data of the patients were obtained from their clinical records. Of 101 cases of mucoepidermoid carcinoma, 34 (34%) and 6 (6%) were positive for CRTC1-MAML2 and CRTC3-MAML2 Fusion Transcripts. However, in the 89 cases of non-mucoepidermoid carcinoma, neither Transcript was noted. In the former cases, CRTC1-MAML2 and CRTC3-MAML2 Fusions were mutually exclusive. The other Fusion, CRTC2-MAML2, was not detected. We confirmed that the clinicopathological features of CRTC1-MAML2-positive mucoepidermoid carcinomas indicated an indolent course. CRTC3-MAML2-positive mucoepidermoid carcinomas also had clinicopathologically favorable features; all cases showed a less advanced clinical stage, negative nodal metastasis, no high-grade tumor histology, and no recurrence or tumor-related death after surgical resection of the tumor. It is interesting to note that patients with CRTC3-MAML2-positive tumors (mean 36 years of age) were significantly younger that those with the CRTC1-MAML2 Fusion (55 years) and those with Fusion-negative tumors (58 years). In conclusion, CRTC3-MAML2 Fusion, which is mutually exclusive with CRTC1-MAML2 Fusion and specific to mucoepidermoid carcinoma, may be detected more frequently than previously expected. Mucoepidermoid carcinomas possessing CRTC3-MAML2 Fusion may be associated with favorable clinicopathological features and patients may be younger than those with CRTC1-MAML2 Fusion or those with no detectable gene Fusion.
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prognostic significance of p27kip1 ki 67 and crtc1 maml2 Fusion Transcript in mucoepidermoid carcinoma a molecular and clinicopathologic study of 101 cases
Journal of Oral and Maxillofacial Surgery, 2009Co-Authors: Satoru Miyabe, Mitsukuni Okabe, Motoo Yokoi, Kei Ijichi, Akira Inagaki, Noriyuki Nagai, Hitoshi Nagatsuka, Tadaaki Eimoto, Yasuhisa Hasegawa, Kazuo ShimozatoAbstract:Purpose Mucoepidermoid carcinoma (MEC) is the most frequently detected primary malignancy of the salivary gland and is characterized by a marked variation in prognosis. In the present study, we investigated the prognostic significance of p27 Kip1 , Ki-67, and CRTC1 (also called MECT1 , TORC1 , and WAMTP1 )- MAML2 Fusion in MEC. Materials and Methods MEC cases (n = 101) were examined for p27 Kip1 and Ki-67 expression using immunohistochemistry and for CRTC1 - MAML2 Fusion Transcript using reverse Transcriptase-polymerase chain reaction. Results p27 Kip1 , Ki-67, and the CRTC1 - MAML2 Fusion Transcript were expressed in 71, 31, and 34 of the 101 cases, respectively. p27 Kip1 and CRTC1 - MAML2 Fusion were associated with favorable clinicopathologic tumor features and Ki-67 with aggressive clinicopathologic features. Multivariate survival analyses were performed that included the following 10 clinicopathologic factors: age, gender, tumor site, tumor size, nodal metastasis, clinical stage, histologic grade, p27 expression, Ki-67 expression, and CRTC1 - MAML2 Fusion. For disease-free survival, only p27 Kip1 expression was significant as an independent prognostic factor. For overall survival, p27 Kip1 expression, CRTC1 - MAML2 Fusion, and tumor size were significant. In each analysis, p27 Kip1 and CRTC1 - MAML2 Fusion were independent of the clinical stage. Ki-67 expression was not selected in either multivariate analysis. Conclusions p27 Kip1 and CRTC1 - MAML2 Fusion were associated with favorable clinicopathologic tumor features, and both were useful in predicting the overall survival of patients with MEC. For disease-free survival, p27 Kip1 might be the most useful prognostic factor. In contrast, Ki-67 might not be a very powerful prognostic indicator for either survival point.
Julia A Bridge - One of the best experts on this subject based on the ideXlab platform.
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inconspicuous insertion 22 12 in myxoid round cell liposarcoma accompanied by the secondary structural abnormality der 16 t 1 16
The Journal of Molecular Diagnostics, 2003Co-Authors: Nathan C Birch, James R Neff, Marilu Nelson, Cristina R Antonescu, Lisa Sarran, Thomas A Seemayer, Julia A BridgeAbstract:In myxoid/round cell liposarcoma, the t(12;16)(q13;p11) and its associated Fusion Transcript, FUS-CHOP, characterize greater than 95% of cases. The variant translocation t(12;22)(q13;q12) and associated EWS-CHOP Fusion Transcript are rare. A second non-random aberration observed in roughly 20% of Ewing's sarcomas, and to a lesser extent other select sarcomas, is the unbalanced 1;16 translocation. Recognition of this secondary aberration in the absence of an obvious primary karyotypic abnormality strongly suggests that the use of other genetic approaches will be informative in uncovering a clinically suspected primary anomaly. The following case illustrates the utility of molecular cytogenetic and reverse Transcriptase-polymerase chain reaction techniques in diagnosing an ins(22;12)(q12;q13q14) and associated EWS-CHOP Fusion Transcript in a myxoid/round cell liposarcoma exhibiting a der(16)t(1;16)(q11;q11).
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genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma whereas amplification predominates in embryonal with anaplasia and alveolar subtypes
Genes Chromosomes and Cancer, 2002Co-Authors: Julia A Bridge, Poul H Sorensen, Stephen J Qualman, Ron Suijkerbuijk, Gail D Wenger, Ji Zhang, Scott K Baker, Frederic G BarrAbstract:In this investigation, we selected PAX3/FKHR and PAX7/FKHR Fusion Transcript–positive and –negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS Fusion Transcript subtypes, providing evidence for a genetic kinship despite the absence of a Fusion Transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGF1R possibly plays a role in the development or progression of a subset of rhabdomyosarcomas. © 2002 Wiley-Liss, Inc.
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genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma whereas amplification predominates in embryonal with anaplasia and alveolar subtypes
Genes Chromosomes and Cancer, 2002Co-Authors: Julia A Bridge, Poul H Sorensen, Stephen J Qualman, Ron Suijkerbuijk, Gail D Wenger, Ji Zhang, Scott K Baker, Frederic G BarrAbstract:In this investigation, we selected PAX3/FKHR and PAX7/FKHR Fusion Transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS Fusion Transcript subtypes, providing evidence for a genetic kinship despite the absence of a Fusion Transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGF1R possibly plays a role in the development or progression of a subset of rhabdomyosarcomas.
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prognostic impact of p53 status tls chop Fusion Transcript structure and histological grade in myxoid liposarcoma a molecular and clinicopathologic study of 82 cases
Clinical Cancer Research, 2001Co-Authors: Cristina R Antonescu, Julia A Bridge, James R Neff, Sylvia J Tschernyavsky, Ramona Decuseara, Denis H Y Leung, James M Woodruff, Murray F Brennan, John R Goldblum, Marc LadanyiAbstract:Purpose: A specific TLS-CHOP Fusion gene resulting from the t(12;16) is present in at least 95% of myxoid liposarcomas (MLS). Three common forms of the TLS-CHOP Fusion have been described, differing by the presence or absence of TLS exons 6–8 in the Fusion product. Type 5-2 (also known as type II) consists of TLS exons 1–5 fused to CHOP exon 2; type 7-2 (also known as type I) also includes TLS exons 6 and 7 in the Fusion, whereas type 8-2 (also known as type III) fuses TLS exons 1–8 to CHOP exon 2. We sought to determine the impact of TLS-CHOP Fusion Transcript structure on clinical outcome in a group of well-characterized MLS cases. We also analyzed P53 status, because this parameter has been found to have a significant prognostic impact in other sarcomas with chromosomal translocations. Methods: We analyzed TLS-CHOP Fusion Transcripts by reverse-Transcription PCR using RNA extracted from frozen tissue in 82 MLS confirmed previously to harbor a CHOP rearrangement either by Southern blotting or by cytogenetic detection of the t(12;16). Parameters analyzed included age, location, size, percentage of round cell (RC) component, areas of increased cellularity, necrosis, and surgical margins. In 71 (87%) cases, adequate tumor tissue was available for immunohistochemical analysis of P53 status, using DO7 antibody. The Kaplan-Meier method, log-rank, and Cox regression tests were used for survival analyses. Results: Most MLS were >10 cm (73%), arising in the thigh (70%), and localized at presentation (89%). RC component was TLS-CHOP Fusion Transcript was type 5-2 in 55 (67%), type 7-2 in 16 cases (20%), and type 8-2 in 8 (10%). One tumor had a unique variant Fusion, between exon 6 TLS and exon 2 CHOP . Two other cases (2%) showed an EWS-CHOP Fusion Transcript. Overexpression of P53 (defined as ≥10% nuclear staining) was detected in 12 (17%) cases. High histological grade (defined as ≥5% RC; P P P P P = 0.02) were found to be significant in predicting local recurrence in the entire group as well as localized cases by univariate and multivariate analysis. Although there was no significant correlation between TLS-CHOP Transcript type and histological grade or disease-specific survival, an association was found between the P53 status and type 5-2 Fusion ( P Conclusion: In contrast to some other translocation-associated sarcomas, the molecular variability of TLS-CHOP Fusion Transcript structure does not appear to have a significant impact on clinical outcome in MLS. Instead, high histological grade (≥5% RC), presence of necrosis, and P53 overexpression are predictors of unfavorable outcome in localized MLS.
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primary monophasic synovial sarcoma of the pleura five cases confirmed by the presence of syt ssx Fusion Transcript
The American Journal of Surgical Pathology, 2001Co-Authors: Marie Christine Aubry, Julia A Bridge, Robert Wickert, Henry D TazelaarAbstract:This study reports five cases of primary pleural monophasic synovial sarcomas and assesses the role of the SYT-SSX Fusion Transcript in the differential diagnosis. Patients had a mean age of 47 years with no gender predilection. Chest pain and pleural-based masses with efFusions characterized the clinical presentations. Each patient underwent a complete surgical resection of the mass. The mean follow-up was 9 months, available in four patients. They were all alive, with no evidence of disease. Histologically, neoplasms were composed of densely packed fusiform cells focally alternating with less cellular areas. No epithelial differentiation was identified at the hematoxylin and eosin level. Keratin and epithelial membrane antigen reactivity was focal and present in four and two tumors, respectively. There was no immunoreactivity for CD34. RT-PCR studies for the presence of a SYT-SSX1 or SYT-SSX2 Fusion Transcript were positive in every tumor. In comparison, 10 localized fibrous tumors were immunohistochemically negative for keratin and epithelial membrane antigen and positive for CD34. A SYT-SSX Fusion Transcript was not identified in any of five localized fibrous tumors tested. Identification of the synovial sarcoma-specific chimeric Transcript (SYT-SSX1 or SYT-SSX2), in conjunction with immunoperoxidase studies, can be extremely helpful in identifying cases of pleural monophasic synovial sarcoma.
