Orbital rhabdomyosarcoma: relationship between DNA ploidy, p53, bcl-2, MDR-1 and Ki67 (MIB1) expression and clinical behavior.
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.
Staibano
Stefania
S
Department of Biomorphological and Functional Sciences, Pathology Section, University of Naples Federico II, Italy. amando.tedeschi@virgilio.it
Franco
Renato
R
Tranfa
Fausto
F
Mezza
Ernesto
E
Lo Muzio
Lorenzo
L
Strianese
Diego
D
Errico
Maria Elena
ME
Bufo
Pantaleo
P
Ferrara
Gerardo
G
Somma
Pasquale
P
Mansueto
Gelsomina
G
Greco
Immacolata
I
Fiorillo
Amedeo
A
Bonavolontà
Giulio
G
De Rosa
Gaetano
G
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
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