Aberrant expression of tumor suppressor proteins in the Ewing family of tumors.

  title={Aberrant expression of tumor suppressor proteins in the Ewing family of tumors.},
  author={A Maitra and Helen Roberts and Arthur G. Weinberg and Joseph Geradts},
  journal={Archives of pathology \& laboratory medicine},
  volume={125 9},
BACKGROUND Deregulation of tumor suppressor gene function and abrogation of cell cycle control are common features of malignant neoplasms, but corresponding data on Ewing sarcomas and primitive neuroectodermal tumors are relatively scarce. We studied the expression of 4 tumor suppressor proteins in the Ewing family of tumors (EFTs). DESIGN We examined a series of 20 pediatric EFTs for abnormal expression of p16(INK4a), p14(ARF), p21(WAF1), and pRB by immunohistochemical analysis of… 

Clinicopathological significance of cell cycle regulation markers in a large series of genetically confirmed Ewing's Sarcoma Family of Tumors

It is demonstrated that Ki67 expression constitutes a valuable indicator of poor prognosis in localized ESFT, being especially relevant in the group of patients which incorporated radiotherapy in their regimen schedules.

Role of p16/INK4a in gastrointestinal stromal tumor progression.

Because the p16 locus is involved consistently in chromosomal losses found in malignant gastrointestinal stromal tumors (GISTs), we studied p16 in a series of 21 GISTs with complete follow-up using

Expression of C-kit in Ewing Family of Tumors: A Comparison of Different Immunohistochemical Protocols

  • Atif A AhmedE. Gilbert-BarnessA. Lacson
  • Biology, Medicine
    Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
  • 2004
It is concluded that c-kit is variably expressed in Ewing sarcoma, using either monoclonal or polyclonal antibodies.

Regulation of apoptosis and proliferation in Ewing's sarcoma—opportunities for targeted therapy

This review will focus on the regulation of major pathways of proliferation and apoptosis in tumors of the Ewing's sarcoma family and point out how modulation of these pathways might be of potential use for future therapy.

Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse.

Alterations in p53 or p16/p14ARF are found in a fourth of ES cases and define a subset with highly aggressive behavior and poor chemoresponse, which is the first combined prognostic analysis of these three molecular parameters in ES.

Molecular genetics of Ewing sarcoma, model systems and finding novel (immuno-) therapeutic targets

The current available knowledge on the genetics underpinning EWS is summarized, the current knowledge of its epigenetic profile is explored, in vitro and in vivo model systems are discussed, and the unravelling knowledge of potential targets for treatment is explored including recent insights into potential immunotherapy.

BMI-1 promotes ewing sarcoma tumorigenicity independent of CDKN2A repression.

The data show that BMI-1 is highly expressed by ESFT cells and that, although it does not significantly affect proliferation or survival, BMI- 1 actively promotes anchorage-independent growth in vitro and tumorigenicity in vivo, suggesting that its oncogenic function in these tumors is in part mediated through modulation of adhesion pathways.

Chromosome 9p21 gene copy number and prognostic significance of p16 in ESFT

It is demonstrated that loss (homozygous deletion or single copy) of CDKN2A was not prognostically significant in primary ESFT, and high levels of p16/p14ARF mRNA expression were predictive of a poor event-free survival and should be investigated further.

Molecular abnormalities in Ewing’s sarcoma

  • S. Burchill
  • Medicine, Biology
    Expert review of anticancer therapy
  • 2008
Increased understanding of the molecular events that arise in ESFT and their role in the development and maintenance of the malignant phenotype will inform the improved stratification of patients for therapy and identify targets and pathways for the design of more effective cancer therapeutics.

Comparative characteristics of small cell lung cancer and Ewing’s sarcoma: a narrative review

  • G. Hamilton
  • Medicine, Biology
    Translational lung cancer research
  • 2022
The global chemoresistance of SCLC and ES may be explained by physiological resistance at the tumor level and formation of larger spheroids that contain quiescent and hypoxic tumor cells in regions that occlude therapeutics.



The Ewing family of tumors--a subgroup of small-round-cell tumors defined by specific chimeric transcripts.

A subgroup of small-round-cell tumors identified as belonging to the Ewing family of tumors can be defined according to a specific molecular genetic lesion that is detectable by a rapid, reliable, and efficient method.

Rb and p16INK4a expression in resected non-small cell lung tumors.

The prognostic significance of the absence of p16INK4, in resected NSCLC is established and the critical importance of disrupting the pathway of cyclin-dependent kinase-mediated phosphorylation of pRB in the molecular oncogenesis and progression of NSCLCs is confirmed.

Loss of p16INK4a expression correlates with decreased survival in pediatric osteosarcomas

Immunohistochemical analysis of p16INK4a expression in pediatric osteosarcomas may be a useful adjunctive marker of prognosis and significantly correlated with decreased survival in univariate analysis, while loss of pRB expression did not affect survival.

Effect of p21WAF1/CIP1 expression on tumor progression in bladder cancer.

Maintenance of p21 expression appears to abrogate the deleterious effects of p53 alterations on bladder cancer progression, and p21expression was an independent predictor of tumor recurrence and survival when assessed with tumor grade, tumor stage, lymph node status, and tumor p53 status.

Ewing's sarcoma and peripheral primitive neuroectodermal tumors after their genetic union.

  • H. Kovar
  • Medicine
    Current opinion in oncology
  • 1998
Increasing experimental data suggest that EWS-ets fusions act as transforming transcription factors, and the presence of metastases at diagnosis as the major predictor of outcome has been assessed on a submicroscopic level by reverse transcriptase-polymerase chain reaction.

Mutational alteration of the p16CDKN2a tumor suppressor gene is infrequent in Ewing's sarcoma.

The results strongly suggest that the mutational inactivation of the p16CDKN2a gene might be a rare event, and thus not play a critical role in the pathogenesis of Ewing's sarcoma.

Among genes involved in the RB dependent cell cycle regulatory cascade, the p16 tumor suppressor gene is frequently lost in the Ewing family of tumors

The data indicate that, despite the absence of cytogenetically detectable 9p21 chromosomal aberrations, p16 deletions constitute the most frequent secondary molecular aberration in Ewing tumors so far.

Immunohistochemical p16INK4a analysis of archival tumors with deletion, hypermethylation, or mutation of the CDKN2/MTS1 gene. A comparison of four commercial antibodies.

For tumor types in which p16 mutations are uncommon, the PharMingen polyclonal antibody may be a suitable alternative, and monoclonals DCS-50 and ZJ11 the least specific for wild-type p16.