p16INK4A (CDKN2A) gene deletion is a frequent genetic event in synovial sarcomas

Department of Pathology, Medical School, University of Valencia, Spain.
American Journal of Clinical Pathology (Impact Factor: 2.51). 01/2007; 126(6):866-74. DOI: 10.1309/E2AAY2XXN431WL81
Source: PubMed


We assessed the frequency of genomic deletion of p16INK4A (CDKN2A) in synovial sarcomas (SSs) and its possible association with immunoexpression of p16 and cyclin D1 and the Ki-67 proliferation index using dual-color fluorescence in situ hybridization (FISH) on tissue microarray sections of 41 histologically and molecularly confirmed SSs. A heterozygous p16INK4A gene deletion was identified in 28 (74%) of 38 cases, with 25 (89%) of them showing abnormal p16 protein expression (20 negative and 5 heterogeneous). Of 25 cases, 19 (76%) exhibiting increased cyclin D1expression also demonstrated heterozygous p16INK4A deletion. No significant association was observed between p16INK4A deletion and Ki-67 proliferation index, tumor grade, or histologic subtype. Our results demonstrate that p16INK4A (CDKN2A) gene deletion is a frequent genetic event in SS.

Download full-text


Available from: José Antonio López-Guerrero,
43 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuroblastic tumors (NT) are pediatric neoplasms with a heterogeneous genetic profile. They present genotypic alterations of prognostic value, the study of which is mandatory in designing therapeutic management. Tissue microarrays (TMA) from paraffin material allow the analysis of a large number of cases with minimal costs. The main purpose of the present study is to analyze specific genetic markers of neuroblastic tumors included in TMAs and determine their prognostic value. We compare the results obtained by different molecular techniques at different substrates to evaluate the feasibility of these assays. One hundred thirty-nine samples were included in four different TMAs. We performed FISH assays to determine the status of MYCN gene, 1p36 region and 17q23 arm. The prognostic value of the genetic markers as well as the statistical correlation among clinical variables and outcome were analyzed by SPSS. MYCN amplification was detected in 35.3% of the cases, whereas 1p36 deletion and 17q23 gain was observed in 46.8% and 58.3% of the cases, respectively. An adverse prognosis was noted among these patients. Other adverse factors were age (>18 months) as well as high stage of disease (stage 4). Phenotypic signs of differentiation correlated with good outcome. Retrospective studies using paraffin-embedded tissues assembled in TMA are a useful tool for the analysis of prognostic factors in NT.
    Pediatric Blood & Cancer 02/2009; 52(2):209-14. DOI:10.1002/pbc.21833 · 2.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A total of 50 neuroblastomas were assessed for frequency of ALK gene copy number aberrations by interphase fluorescence in situ hybridization using a break-apart fluorescence in situ hybridization probe. The data were compared with status of MYCN, 11q, 17q, and 1p36. We observed ALK aberrations (amplification, 1 of 45; gain, 15 of 45 and loss/imbalance, 11 of 45) in a total of 27 (60%) of 45 neuroblastomas. Synchronic MYCN and ALK aberrations accounted for 23 of 45 (51%) tumors; however, MYCN alterations were also detected in 11 (60%) of 18 tumors without ALK aberrations. Our data suggest that copy number aberrations of the ALK gene is a frequent genetic event in the development of neuroblastomas. In addition, no correlation was observed between ALK aberrations and alterations of 11q, 17q, and 1p36.
    Human pathology 09/2009; 40(11):1638-42. DOI:10.1016/j.humpath.2009.05.002 · 2.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To compare the sensitivity and specificity of fluorescence in situ hybridization (FISH) with reverse transcription polymerase chain reaction (RT-PCR) in the diagnosis of Ewing sarcoma family of tumors (ESFTs) and other small round-cell tumors (SRCTs) in formalin-fixed paraffin-embedded tissue assembled in tissue microarrays (TMAs). The second objective is to confirm the value of molecular methods and immunohistochemical (IHC) assays, to perform a differential diagnosis between ESFTs and SRCTs with similar or overlapping morphology. A total of 560 cases were selected for the present study out the 806 cases collected from the PROgnosis and THerapeutic Targets in the Ewing's Family of TumorS project. Case selection bias included only the cases with enough material to enable the TMA construction, as FISH analysis and the majority of IHC studies were performed in TMAs. Histopathologic, IHC, and molecular assays were carried out. Of the 560 total cases, 411 (73.4%) were considered informative (with results by FISH and/or RT-PCR assays). From the informative cases, 382 (92.9%) were diagnosed as ESFT, 23 cases (5.6%) as non-ESFT but with specific diagnosis for another established entity, and 6 cases (1.5%) as small round cell tumors not otherwise specified. Sensitivity and specificity for the FISH assays was 96.3% and 95.2%, respectively, whereas RT-PCR presented a sensitivity of 97.5% and specificity of 92.9%. In concordant cases, both methods showed a sensitivity and specificity of 99.2% and 100%, respectively. Twenty-nine cases (7.1%) initially interpreted at morphologic level as atypical ESFTs were finally reclassified, with the support of molecular methods and IHC, as either non-ESFT with another specific histologic type or as small round cell tumors not otherwise specified. FISH and RT-PCR are ancillary techniques possessing high sensitivity in the diagnosis of ESFT; nevertheless, FISH is more specific than RT-PCR in the diagnosis of formalin-fixed paraffin-embedded tissue. Both methods in combination displayed the highest sensitivity and specificity. The combination of histopathologic, IHC, and molecular findings is the method of choice for the diagnosis of ESFT, as well as for the differential diagnosis with other SRCTs.
    Diagnostic molecular pathology: the American journal of surgical pathology, part B 10/2009; 18(4):189-99. DOI:10.1097/PDM.0b013e3181a06f66 · 2.28 Impact Factor
Show more