Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0035412 (rhabdomyosarcoma)
6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of a 13-year-old girl with soft tissue sarcoma of the hand, which showed muscle and neuroectodermal immunophenotypes. Molecular studies were performed on RNA collected from fine-needle aspiration (FNA) cytology and peripheral blood samples by nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. This biphenotypic tumor showed simultaneous expression of EWS-FLI1 and PAX3-FKHR transcripts, specific of Ewing family tumors and alveolar rhabdomyosarcoma, respectively. Although childhood sarcomas with simultaneous muscle and neural differentiation have been described to have EWS-FLI1 transcripts, there are no reports of tumors with both transcripts. Cytological specimens are a good source of RNA for molecular studies.
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PMID:Molecular features in a biphenotypic small cell sarcoma with neuroectodermal and muscle differentiation. 949 Feb 79

PAX3, a member of the PAX-gene family, encodes a nuclear transcription factor that is transiently expressed in the neural tube and in muscle progenitor cells and regulates embryonal development in the mouse. Together with the FKHR gene it is involved in the t(2;13)(q35;q14), a specific translocation associated with alveolar rhabdomyosarcoma (ARMS). As a consequence of the rearrangement two chimeric transcripts originate: FKHR-PAX3 and PAX3-FKHR. We studied the expression of wild type PAX3 and the chimeric transcripts originating from the t(2;13) in a series of 23 rhabdomyosarcomas (RMS) of childhood, by reverse transcriptase polymerase chain reaction (RT-PCR). Wild type PAX3 was detected in 48% of the RMS, whereas another 39% were positive only after nested PCR. Normal adult-skeletal muscle showed a very weak expression of PAX3, but fetal muscle did not express PAX3. PAX3-FKHR was found in 11 of 15 alveolar RMS, 7 of which were positive also for the reciprocal transcript, whereas no RMS expressed FKHR-PAX3 alone. These results confirm that the PAX3-FKHR transcript is specifically associated with the alveolar RMS and that it is a more sensitive marker of the t(2;13) than the reciprocal product FKHR-PAX3. Furthermore, the finding of PAX3 expression with or without PAX3-FKHR transcript in the great majority of the cases raises the question of whether PAX3 expression could play a role in the pathogenesis of RMS.
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PMID:Normal and rearranged PAX3 expression in human rhabdomyosarcoma. 954 61

We reviewed six cases of rhabdomyosarcoma as a rare second primary malignancy in children with bilateral retinoblastoma after irradiation treatment. The patients comprised four females and two males (age range 1 year 4 months-7 years 11 months). Second tumors arose in the temporal muscle inside or close to the previously irradiated fields. All the children were alive and well 24-72 months after diagnosis. Microscopic examination showed proliferation of closely packed, small round cells with scanty cytoplasm, coarse nuclear chromatin, and increased mitotic activity without a myxoid background nor obvious alveolar architecture. The most characteristic feature was the presence of rosette-like structures in four tumors. Immunoreactivity for many skeletal muscle markers was evident, including desmin (six of six), muscle-specific actin (HHF35) (six of six), sarcomeric actin (six of six), myogenin (six of six), vimentin (six of six), and myoglobin (three of six). On reverse transcriptase-polymerase chain reaction examination, three second tumors lacked specific chimeric transcripts for alveolar rhabdomyosarcoma and Ewing's sarcoma. Unexpectedly, variable reactivity for neurofilament (150 kd) was identified in six of six second tumors as well as 15 of 20 sporadic primary rhabdomyosarcomas (75%) examined as controls, the result being confirmed by Western blot analysis. In addition, staining for retinoblastoma-susceptibility gene protein was negative in all second tumors, in contrast to positivity in 14 of 17 sporadic primary tumors (82%). This finding suggests that retinoblastoma-susceptibility gene abnormalities could be associated with the development of second primary rhabdomyosarcoma. We consider that knowledge of the occurrence of rhabdomyosarcoma and appropriate immunohistochemical study are helpful for avoiding a misdiagnosis of recurrent retinoblastoma or Ewing's sarcoma when encountering patients with a history of bilateral retinoblastoma who developed second small round cell neoplasms.
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PMID:Second primary rhabdomyosarcomas in patients with bilateral retinoblastoma: a clinicopathologic and immunohistochemical study. 980 27

Rhabdomyosarcomas are a heterogeneous group of tumors with respect to their molecular basis, degree of differentiation, histology, and clinical behavior. Because of the wide variation of tumor morphology, it is often difficult to distinguish between the distinct subtypes of rhabdomyosarcomas. By using cryosections of tumor specimens and immunohistochemistry, in the present study we show that strong expression of myogenin in rhabdomyosarcoma is associated with alveolar histology (P = <0.0001, Fisher's exact test). Although staining for myogenin was observed in 22 of 26 rhabdomyosarcomas, all alveolar rhabdomyosarcomas (nine of nine) showed high levels of staining for myogenin, as defined by the frequency and intensity of staining of the tumor cells. The staining pattern suggests that the tumor cells are clonally derived from myogenin-positive progenitor cells. In contrast, most embryonal rhabdomyosarcomas (13 of 15) were either negative or showed a low level of staining for myogenin. In these tumors a larger proportion of tumor cells were distinctly negative for myogenin. Six of seven alveolar rhabdomyosarcomas that strongly stained for myogenin were also positive for Pax3-7/Forkhead (FKHR) by polymerase chain reaction/reverse transcriptase-polymerase chain reaction. One of two embryonal rhabdomyosarcomas that strongly stained for myogenin was retrospectively found to be positive for Pax3/FKHR transcripts. Quantitative analysis for myogenin by Western blotting using a smaller subset of rhabdomyosarcomas revealed that in general there was a good correlation between immunohistochemical staining and Western blotting (P = 0.01, Pearson Correlation), although the former technique was more sensitive for detecting tumors with low levels of the protein. On average, alveolar rhabdomyosarcomas expressed at least threefold more myogenin than embryonal rhabdomyosarcomas. Our data show that staining for myogenin will be a simple, rapid, and accurate adjunct for distinguishing between alveolar and embryonal rhabdomyosarcomas. We propose that embryonal rhabdomyosarcomas result from an early block in myogenesis, before the expression of myogenin. In contrast, we propose that alveolar rhabdomyosarcomas either originate from a late block in myogenesis (after expression of myogenin) or that the pathological mechanisms involved in these neoplasms also induce strong expression of this protein.
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PMID:Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass. 1066 68

Rhabdomyosarcoma may be divided into three subtypes--embryonal, alveolar, and undifferentiated sarcoma--which can be distinguished by molecular analysis. The authors applied reverse transcriptase-polymerase chain reaction analysis (RT-PCR) to analyze tumor samples from 14 children with rhabdomyosarcoma for the presence of the chimeric PAX3-FKHR transcript resulting from the translocation t(2;13)(q35,q14). Both fresh and paraffin-embedded tissues were used. In only nine specimens was the RNA intact for the analysis. The chimeric transcript was identified in seven samples: four alveolar type, one embryonal type, and two undifferentiated sarcoma. Histologic review was performed in the three samples with discordance between the molecular and histologic findings. A sample from a patient with a diagnosis of embryonal rhabdomyosarcoma on presentation and expression of PAX3-FKHR fusion transcript yielded a small focus of alveolar rhabdomyosarcoma and was reclassified as alveolar rhabdomyosarcoma. One of the samples from a patient with undifferentiated sarcoma was redefined as alveolar subtype; the diagnosis of the second undifferentiated sarcoma remained unchanged, in accordance with the histologic diagnosis. These findings further support the recommendation that molecular analysis be included in the diagnostic workup of childhood small round cell tumors to reach a more accurate diagnosis for tailoring of specific treatment.
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PMID:Clinical relevance of molecular diagnosis in childhood rhabdomyosarcoma. 1071 7

Alveolar rhabdomyosarcoma (ARMS) is associated with the specific chromosomal translocation (2;13)(q35;q14) or its rarer variant t(1;13)(p36;q14), which produces the fusion gene PAX7-FKHR. Here we describe the human cell line RC2, derived from an ARMS, which harbors a cryptic t(1;13)(p36;q14) and concomitantly shows amplification of the PAX7-FKHR fusion gene and of the MYCN oncogene. The t(1;13) and MYCN oncogene were studied by standard cytogenetic analysis and molecular techniques. The reverse transcriptase polymerase chain reaction demonstrated the expression of PAX7-FKHR mRNA in RC2 cells, although karyotype analysis failed to demonstrate a t(1;13)(p36;q14) chromosomal translocation or a derivative 13 chromosome. Double minute chromosomes were detected in all the metaphases studied. Fluorescence in situ hybridization analysis revealed multiple copies of the PAX7-FKHR fusion gene localized exclusively on a subset of double minutes, whereas multiple copies of MYCN were identified on other double minute chromosomes. Southern-blot analysis demonstrated that RC2 cells contain approximately 20 copies of the MYCN oncogene. So far no continuous RMS cell line carrying the t(1;13)(p36;q14) has been described, and PAX7-FKHR and MYCN amplifications have always been reported to occur separately in rhabdomyosarcoma (RMS). The availability of an ARMS cell line that harbors the t(1;13)(p36;q14) constitutes a useful tool for further understanding the role of the PAX7-FKHR fusion gene in RMS oncogenesis and may improve knowledge of the possible relation between PAX7-FKHR and MYCN amplification.
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PMID:Concomitant amplification and expression of PAX7-FKHR and MYCN in a human rhabdomyosarcoma cell line carrying a cryptic t(1;13)(p36;q14). 1106 97

The reverse transcriptase polymerase chain reaction (RT-PCR) provides a technique to diagnose a group of sarcomas and small round cell tumors that contain specific chromosomal translocations and chimeric gene fusion products. We adapted real-time qualitative RT-PCR to utilize dual-labeled, fluorogenic, TaqMan probes, which hybridize to targets that overlap the junction of the chimeric gene fusions in alveolar rhabdomyosarcoma (ARMS), synovial sarcoma (SS), and desmoplastic small round cell tumor (DSRCT). Assays were confirmed on cell lines and tissue samples; appropriate negative amplification assays were obtained when each tumor-specific probe and primer set was used on different neoplasms and cell lines that were not expected to harbor the specific translocations and chimeric gene fusions. Although our cases are few, we speculate that as more molecular variants of ARMS, SS, and DSRCT are discovered, clinical correlations based on precise molecular features will be required and fusion site specificity will be assured by the use of junction-based TaqMan probes.
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PMID:TaqMan junction probes and the reverse transcriptase polymerase chain reaction: detection of alveolar rhabdomyosarcoma, synovial sarcoma, and desmoplastic small round cell tumor. 1217 83

Transforming growth factor-beta (TGF-beta) belongs to a superfamily of structurally related polypeptides involved in various biological processes, including cell growth, proliferation and differentiation, angiogenesis, apoptosis, and extracellular matrix remodeling. We tried to define the different expression patterns of the TGF-beta receptors by investigating the female reproductive organs during the menstrual cycle and endometrial tumorigenesis, because their role in these processes is still unclear. In this study, we examined the expression of the TGF-beta type I and type II receptors in normal (n=13) and carcinomatous (n=42) endometrial tissue specimens using reverse transcriptase polymerase chain reaction and immunological (Western blot and enzyme linked immunosorbent assay) methods. Two uncommon female genital tract tumors, rhabdomyosarcoma of the uterine cervix and uterine carcinosarcoma, were also included. There were no significant differences between normal and cancerous endometrial tissues regarding the TGF-beta receptors mRNA levels. However, we observed a markedly low TGF-beta type I receptor protein level (P<0.028; Mann-Whitney-U test), while the malignant endometrium showed a significantly higher TGF-beta type II receptor protein level (P<0.007; Mann-Whitney-U test) than the normal endometrium. Moreover, significantly elevated TGF-beta receptor type II protein level was noted when depth of myometrial invasion of endometrial carcinomas was considered (P<0.05; Mann-Whitney-U test). In contrast to uterine carcinosarcoma, in which no detectable mRNA for TGF-beta type II receptor was found, we noted expression of both TGF-beta receptors in rhabdomyosarcoma of the uterine cervix. However, neither rhabdomyosarcoma of the uterine cervix nor uterine carcinosarcoma displayed TGFbetaRI and TGFbetaRII protein expression. This observation corroborates the complexity of the deregulation of TGF-beta receptor expression in human endometrial cancer.
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PMID:Expression of TGF-beta type I and II receptors in normal and cancerous human endometrium. 1221 93

Rhabdomyosarcomas (RMSs) are classified into embryonal (ERMS), alveolar (ARMS), and pleomorphic (PRMS) subtypes. ERMS, including botryoid variants, typically occurs in young children, ARMS typically occurs in older children and young adults, and PRMS occurs in older adults. Although ARMSs show thin fibrous bands separating nests of cells, abundant extracellular matrix production is rare in RMS. In the course of reviewing hyalinizing sarcomas we discovered a distinctive RMS in adults that closely mimicked osteosarcoma or chondrosarcoma because of the extensive matrix production. Four RMSs with hyalinized matrix were retrieved from our files. These cases were evaluated with respect to patient age and sex, tumor site and size, growth pattern, nuclear grade, cellularity, mitotic figures/20 high power fields, vascular invasion, necrosis, the presence of rhabdomyoblasts, multinucleated cells, and alveolar growth pattern. Immunohistochemistry for desmin, myogenin, MyoD1, actin, cytokeratin, S-100 protein, collagen II, and CD99 was performed. Reverse transcriptase polymerase chain reaction for the ARMS-associated PAX3/FKHR and PAX7/PKHF was also performed on three cases. The cases involved the forearm, hand, orbit, and nasopharynx of a 40-year-old woman, a 50-year-old man, an 18-year-old man, and a 21-year-old man, respectively. The tumors ranged from 3.7 to 8 cm and consisted of lobules and infiltrating cords of small round malignant cells embedded in a densely hyalinized matrix having both a chondroid and osteoid-like appearance. No definite lacunae or matrix calcification was present. An alveolar pattern was only present focally, and tumor giant cells were not present. One case had a single focus of rhabdomyoblastic differentiation with strap cells. Mitotic activity was >20 mitotic figures/20 high power fields in three of four cases. Immunohistochemically, one case strongly expressed desmin, whereas three cases expressed it focally, with a dot-like pattern. Myogenin was only focally positive, but MyoD1 was present in nearly every cell of each case. Two cases expressed actin and one expressed CD99. No case expressed cytokeratin, S-100 protein, or collagen II. Only one case contained adequate RNA for reverse transcriptase polymerase chain reaction, and this case was negative for the ARMS-associated gene fusions. Follow-up showed one patient to be dead of metastatic disease at 60 months despite intensive therapy, another patient to be disease free at 26 months, and the third patient to be disease free at 5 months. The fourth case is recent. These cases are a distinctive-appearing rhabdomyosarcoma easily mistaken for variants of chondrosarcoma, osteosarcoma, or even sclerosing epithelioid fibrosarcoma because of their hyalinizing appearance compounded by their typically focal and dot-like desmin expression. These four cases are essentially identical to the three unusual RMSs recently reported by Mentzel and Katenkamp as "sclerosing, pseudovascular rhabdomyosarcoma in adults." Although the focal alveolar architecture and the primitive cytologic appearance of these hyalinizing RMS suggest a relationship with ARMS, the presence of abundant strap cells in one case, the predominant expression of MyoD1 rather than myogenin, and the absence of ARMS-associated fusions genes point more strongly toward a variant of ERMS. However, the late adult age in two cases is unusual for both EMRS and ARMS, suggesting that sclerosing RMS may prove to be a distinct subtype of RMS. Study of additional cases will be necessary to more fully elucidate its place among RMS and its prognostic significance.
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PMID:Sclerosing rhabdomyosarcoma in adults: report of four cases of a hyalinizing, matrix-rich variant of rhabdomyosarcoma that may be confused with osteosarcoma, chondrosarcoma, or angiosarcoma. 1221 74

Pediatric small round cell tumors still pose tremendous diagnostic problems. In difficult cases, the ability to detect tumor-specific gene fusion transcripts for several of these neoplasms, including Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/PNET), synovial sarcoma (SS), alveolar rhabdomyosarcoma (ARMS), and desmoplastic small round cell tumor (DSRCT) using reverse transcriptase-polymerase chain reaction (RT-PCR), can be extremely helpful. Few studies to date, however, have systematically examined several different tumor types for the presence of multiple different fusion transcripts in order to determine the specificity and sensitivity of the RT-PCR method, and no study has addressed this issue for formalin-fixed material. The objectives of this study were to address the specificity, sensitivity, and practicality of such an assay applied strictly to formalin-fixed tissue blocks. Our results demonstrate that, for these tumors, the overall sensitivity for detecting each fusion transcript is similar to that reported in the literature for RT-PCR on fresh or formalin-fixed tissues. The specificity of the assay is very high, being essentially 100% for each primer pair when interpreting the results from visual inspection of agarose gels. However, when these same agarose gels were examined using Southern blotting, a small number of tumors also yielded reproducibly detectable weak signals for unexpected fusion products, in addition to a strong signal for the expected fusion product. Fluorescence in situ hybridization (FISH) studies in one such case indicated that a rearrangement that would account for the unexpected fusion was not present, while another case was equivocal. The overall specificity for each primer pair used in this assay ranged from 94 to 100%. Therefore, RT-PCR using formalin-fixed paraffin-embedded tissue sections can be used to detect chimeric transcripts as a reliable, highly sensitive, and highly specific diagnostic assay. However, we strongly suggest that the final interpretation of the results from this assay be viewed in light of the other features of the case, including clinical history, histology, and immunohistochemistry, by the diagnostic pathologist. Additional studies such as FISH may be useful in clarifying the nature of equivocal or unexpected results.
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PMID:Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissue. 1237 29


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