Immunohistochemical and molecular study of radiation-induced multiple meningiomas with pleural and pulmonary metastasis.
In the present study, the telomerase activity and the putative alterations of genes involved in cell-cycle control (p53, Fas and pRb) were investigated in a radiation-induced meningioma with multiple recurrences and pleural-pulmonary metastases (the patient, a 34-year-old male, had a history of carcinoma of the tongue of testicular lymphocytic lymphoma). Expression of VEGF and vasculature pattern were also studied. Expression of VEGF, pRb and p53 were evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded samples of the tumor. VEGFmRNA was determined by competitive PCR. Fas, FasL and hTERT were evaluated by RT-PCR. Telomerase activity was examined by the TRAP assay. An intense vascularization was observed, supported by high expression of VEGFmRNA (isoforms 121 and 165). pRb and p53 were overexpressed. Fas was undetectable with PCR, whereas FasL was positive. Furthermore, the lesion showed an elevated telomerase activity (TPG, 22), according to the high expression of hTERT. These findings emphasized that even among generally benign neoplasms, such as meningiomas, some highly malignant tumors may develop, as in our case, in which several mechanisms were activated in the cancer progression to guarantee the immortalization of cellular clones (angiogenic phenomenon, activation of telomerase and of anti-apoptotic mechanisms) and the blood spread. Thus, the data illustrate the importance of searching for genetic aberrations (which are a hallmark of malignancy) in meningiomas, as predictive and reliable factors of the possibility to recur and to metastasize.
Department of Surgery, University of Pisa, Italy.
Sabina
S
Pistolesi
Laura
L
Boldrini
Silvia
S
Gisfredi
Katia
K
De Ieso
Tiziano
T
Camacci
Michele
M
Caniglia
Giancarlo
G
Lupi
Raffaele
R
Pingitore
Fulvio
F
Basolo
Pietro
P
Leocata
Giuliano
G
Parenti
Gabriella
G
Fontanini
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D004268:DNA-Binding Proteins; D053222:Fas Ligand Protein; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000556:secondary*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008577:Meningeal Neoplasms / Q000737:chemistry* / Q000209:etiology / Q000473:pathology*; D008579:Meningioma / Q000737:chemistry* / Q000209:etiology / Q000556:secondary*; D010997:Pleural Neoplasms / Q000556:secondary*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000032:analysis; D011878:Radiotherapy / Q000009:adverse effects; D016160:Retinoblastoma Protein / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000032:analysis; D014062:Tongue Neoplasms / Q000532:radiotherapy; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D019014:fas Receptor; D019098:Telomerase