Abnormalities of the p53 gene were found in several classes of soft tissue sarcoma, including leiomyosarcomas, rhabdomyosarcomas and malignant fibrous histiocytomas.
Restriction fragment length polymorphisms (RFLPs) of 2 oncogenes, c-Ha-ras and L-myc, have been analyzed in 101 patients with bone and soft-tissue sarcoma and in 98 normal individuals.
In a preliminary study, we observed that TP53 mutations and nuclear overexpression of p53 protein were frequent events in soft-tissue sarcoma, and we noticed an association between p53-positive phenotype and poor clinical outcome.
The most common cancers occurring in the 41 families with germline p53 mutations, in common with classic LFS, were bone and soft tissue sarcoma, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma, although less than one-half of the probands with germline p53 mutations came from classic LFS families.
The most common soft tissue sarcoma, malignant fibrous histiocytoma (MFH) histopathologically may contain liposarcoma like areas and is often characterized by complex chromosome anomalies, which may include 12q13-15 aberrations, but never as t(12;16).
The intrinsic MDR1 expression in soft tissue sarcoma seemed to depend on certain tumor types, such as liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and fibrosarcoma.
Southern blotting detected complete deletion of p15INK4B and p16INK4 genes in osteosarcomas from 2 patients and a soft tissue sarcoma from another individual.
The intrinsic MDR1 expression in soft tissue sarcoma seemed to depend on certain tumor types, such as liposarcoma, malignant fibrous histiocytoma, leiomyosarcoma, and fibrosarcoma.
Mutation of the p53 tumor suppressor gene, with resultant overexpression of p53 protein, frequently occurs in human soft tissue sarcomas, supporting the role of p53 mutations in the pathogenesis of soft tissue sarcoma and the possible usefulness of p53 immunolocalization as a screening method for p53 mutations.
A tumorigenic connection between the oncogene product Mdm2 and tumor suppressor p53 is generally accepted, but their possible clinical relevance has not yet been investigated sufficiently in soft tissue sarcoma.
The ability to restore wt p53 growth-regulatory functions in soft-tissue sarcoma may ultimately be useful as a future therapy in patients with soft-tissue sarcomas.
Molecular assessment of clonality leads to the identification of a new germ line TP53 mutation associated with malignant cystosarcoma phyllodes and soft tissue sarcoma.
Our results suggest that: (a) alteration of the p16 gene is infrequent in primary soft-tissue sarcoma; (b) Cdk4 may act as an oncogene in soft-tissue sarcoma; and (c) elevated p16 and RB levels might be the result of compensatory up-regulation of these proteins to counteract CDK4 overexpression in these tumors.
Our results suggest that: (a) alteration of the p16 gene is infrequent in primary soft-tissue sarcoma; (b) Cdk4 may act as an oncogene in soft-tissue sarcoma; and (c) elevated p16 and RB levels might be the result of compensatory up-regulation of these proteins to counteract CDK4 overexpression in these tumors.
These data support the involvement of EGF-R and IGF-I-R in the growth and metastasis of human soft tissue sarcoma and may offer new targets for therapeutic intervention in the management of this disease.
Soft tissue sarcoma (STS) also develops, though less frequently, in burn scars. p53 gene mutations were analyzed in paraffin-embedded specimens from 5 patients with STS (4 males and 1 female) that had arisen in a burn scar, by means of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by direct sequencing.
Tumor specimens prior to and following neoadjuvant chemotherapy from 29 cases of high grade soft tissue sarcoma were analyzed with 2 monoclonal antibodies (C494 and JSB-1) that recognize different epitopes of P-glycoprotein.