title: Orbital rhabdomyosarcoma: relationship between DNA ploidy, p53, bcl-2, MDR-1 and Ki67 (MIB1) expression and clinical behavior.
abstract: BACKGROUND
  As for rhabdomyosarcoma (RMS) of other anatomic regions, the evaluation of traditional clinicopathological parameters does not allow the unequivocal outcome prediction of the single cases of orbital RMS. We investigated the role of DNA ploidy and immunohistochemical expression of p53, bcl-2, MDR-1 and Ki67 (MIB1) in the prognostic evaluation of orbital rhabdomyosarcomas.
  
  
  METHODS
  The study population consisted of 11 selected cases. Serial sections of each tumor, stained with Feulgen's technique, were analyzed for the DNA content, using the QUANTIMET 500c Leica analyzer, QWINVO200A software. The results were compared with the immunohistochemical expression of p53 (wild plus mutated, W&M and mutated), bcl2, MDR-1 and Ki67 (MIB1), and with follow-up data.
  
  
  RESULTS
  The statistical analysis of results showed that the cases of tetraploid and/or multiploid RMS, overexpressing p53 (W&M and mutated) and MDR-1, were characterized by an overall worse prognosis. On the contrary, the tumors with a favourable clinical course showed hyperexpression of MIB1 and absence of mutated p53 expression. Significantly higher MIB1 expression was found in the relapse-free group of tumors, with respect to the RMS with relapse (both in primary tumors and relative relapses, p<0.05). This finding could justify the higher sensibility to pharmacological therapy of RMS of the first group. The group of RMS with a worse prognosis (primary tumors and relapses) showed instead p53 overexpression (W&M and mutated), MDR-1 expression and multiploidy, with high 5cEE values and tetraploid peaks. No significant difference was found concerning the expression of bcl-2 among the two groups of RMS (p>0.05).
  
  
  CONCLUSIONS
  The evaluation of DNA ploidy, p53, MIB1 and MDR-1 expression could be used for subtyping of orbital RMS into two prognostically different subcategories, respectively RMS responder to the therapy, with favourable clinical outcome, and RMS with a worse prognosis, requiring more aggressive therapeutic protocols.
authors.affiliation: Department of Biomorphological and Functional Sciences, Pathology Section, University of Naples Federico II, Italy. amando.tedeschi@virgilio.it
authors.forename: Stefania
authors.initials: S
authors.lastname: Staibano
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Fausto
authors.initials: F
authors.lastname: Tranfa
authors.forename: Ernesto
authors.initials: E
authors.lastname: Mezza
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Lo Muzio
authors.forename: Diego
authors.initials: D
authors.lastname: Strianese
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Errico
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Bufo
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ferrara
authors.forename: Pasquale
authors.initials: P
authors.lastname: Somma
authors.forename: Gelsomina
authors.initials: G
authors.lastname: Mansueto
authors.forename: Immacolata
authors.initials: I
authors.lastname: Greco
authors.forename: Amedeo
authors.initials: A
authors.lastname: Fiorillo
authors.forename: Giulio
authors.initials: G
authors.lastname: Bonavolontà
authors.forename: Gaetano
authors.initials: G
authors.lastname: De Rosa
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D009918:Orbital Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011003:Ploidies; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018233:Rhabdomyosarcoma, Embryonal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53