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Expression of bcl-2 oncoprotein in benign and malignant spindle cell tumors of soft tissue, skin, serosal surfaces, and gastrointestinal tract.

An immunohistochemical study to determine the pattern of immunoreactivity for bcl-2 oncoprotein was performed in 380 spindle cell tumors of soft tissue, skin, serosal surfaces, and gastrointestinal tract. The cases studied included examples of benign, reactive spindle cell proliferations to benign and malignant spindle cell neoplasms, including nodular fasciitis (10), fibromatosis (5), dermatofibroma (10), dermatofibrosarcoma protuberans (18), Kaposi's sarcoma (15), spindle cell lipomatous tumors (24), benign and malignant smooth muscle tumors (35), neural/peripheral nerve sheath neoplasms (53), synovial sarcomas (70) solitary fibrous tumors of serosal surfaces and other sites (56), gastrointestinal stromal tumors (GIST) (47), and malignant undifferentiated fibroblastic spindle cell proliferations of soft tissue (37 cases). The results of bcl-2 staining was additionally correlated with CD34 immunoreactivity. Bcl-2 was uniformly negative in all cases of nodular fasciitis, fibromatosis, and dermatofibroma, as well as in benign and malignant smooth muscle proliferations. Strong positivity for bcl-2 was observed in all cases of spindle cell lipoma, dendritic fibromyxolipoma, Kaposi's sarcoma, solitary fibrous tumors, gastrointestinal stromal tumors, and in the spindle cell component of synovial sarcoma. With the exception of the last, there appeared to be a close correlation between the expression of bcl-2 and CD34 in these tumors. Strong bcl-2 positivity also was found, at least focally, in approximately one third of benign and malignant peripheral nerve sheath tumors, particularly in the better-differentiated (Antoni type A) areas. Sarcomas of fibroblastic type, including low-grade myxofibrosarcoma, malignant fibrous histiocytoma, and fibrosarcoma, showed variable expression of bcl-2 in the tumor cells. Our results appear to indicate that bcl-2 may have a wide distribution among benign and malignant spindle cell neoplasms. Strong expression of this marker in some of these conditions, particularly solitary fibrous tumor, gastrointestinal stromal tumors, and synovial sarcoma, may be of aid for differential diagnosis.

Antigens, CD34↗

Do postvaccinal sarcomas occur in Australian cats?

A soft tissue sarcoma occurred in the interscapular area of a cat, 1 to 7 months after vaccination at that site. The vaccine contained inactivated feline panleucopaenia virus combined with modified live feline herpesvirus and calicivirus. The tumour showed histological features of both fibrosarcoma and malignant fibrous histiocytoma. The tumour was observed to evolve from the site of a presumed postvaccinal granuloma. Local recurrence 6 weeks post excision necessitated more radical resection. Euthanasia was performed 2 years later when pleural effusion developed. The cause of effusion was not determined. There was no palpable evidence of local tumour regrowth at the time of euthanasia. A causal relationship between vaccination and sarcoma formation is considered based on the temporal association between the two events, the anatomical location of the tumour and histopathology consistent with postvaccinal sarcomas reported overseas. Six other vaccine site fibrosarcomas, potentially vaccine associated using the above criteria, are summarised.

Animals↗

Immunotherapy of a murine sarcoma using specific antitumor immune RNA.

The effect of IRNA therapy in a polyoma-induced fibrosarcoma of C3H mice has been studied. Although a protocol that transferred in vitro cytotoxicity was used, no reduction in incidence of tumors, tumor size, or survival was demonstrated. In one experiment, enhancement of tumor growth occurred. It is concluded that cytotoxicity does not reflect in vivo changes and that therapeutic trials of IRNA are premature.

Animals↗

Transplantable sarcomas induced by 3-methylcholanthrene in inbred guinea pigs of JY-1 and Hartley/F strains.

Inbred strains of guinea pigs, JY-1 and Hartley/F, established in this Institute, were injected subcutaneously with 3-methylcholanthrene. During 1972 to 1974, 15 solid tumors (7 fibrosarcomas, 6 liposarcomas, and 2 atheroma-like tumors) have been induced in 12 animals out of 30 employed. Among the 15 tumors, 1 fibrosarcoma induced in JY-1 and 2 liposarcomas and 1 fibrosarcoma induced in Hartley/F were transplantable and established as the syngeneic lines named J4, H10, H12, and H9A, respectively. In addition, a transplant of J4 into the Hartley/F strain animal was established as an allogeneic subline and named JH4. Pathological and biological characteristics of these tumors are described and differences between these tumors and line 10 hepatoma, established by Rapp et al. in strain-2 guinea pig, are discussed.

Animals↗

A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family.

A new acute transforming feline retrovirus, the Hardy-Zuckerman 4 feline sarcoma virus (HZ4-FeSV), has been isolated from a feline fibrosarcoma. The viral genome of HZ4-FeSV contains a new oncogene designated v-kit, has the structure 5' delta gag-kit-delta pol-delta env 3' and specifies a gag-kit polyprotein of relative molecular mass 80,000. The predicted kit amino-acid sequence displays partial homology with tyrosine-specific protein kinase oncogenes. HZ4-FeSV appears to have been generated by transduction of feline c-kit sequences with feline leukaemia virus.

Amino Acid Sequence↗

The induction of intractranial neoplasms by the inoculation of avian sarcoma virus in perinatal and adult rats.

The induction of intracranial neoplasms following the intracerebral inoculation of avian sarcoma virus (ASV) in neonatal mammals is well established. The present study demonstrates the susceptibility of adult rats and compares the incidence and morphology of tumors induced by a uniform inoculum of the Bratislava-77 strain of ASV in adult, neonatal, and fetal Fischer 344 rats. Post-inoculation mortality varied significantly between groups inoculated at 1, 10 and 100 days and was most precipitous in perinatally inoculated rats. Percentage of tumor induction declined from 100% among rats inoculated at 1 day of age to 50% among rats inoculated at 100 days of age. The mean number of tumors/animal was inversely proportional to the logarithm of the age at inoculation. A large majority of tumors in each group were glial; the remainder were mesenchymal and mixed glial and mesenchymal. Neuroglial tumors included: mixed gliomas with oligodendroglial and astrocytic elements; and gemistocytic, pilocytic, fibrillary, anaplastic and protoplasmic astrocytomas. Tumors induced in perinates were more heterogeneous in histological pattern while tumors induced in perinates were more heterogeneous in histological pattern while tumors induced in older animals tended to be purely astrocytic and of uniform cell type. Mesenchymal tumors occurred primarily in the meninges and were common among animals inoculated perinatally but were rare among animals inoculated as adults. No neuronal tumors were encountered even among rats inoculated as early as 16 days of gestation.

Age Factors↗

[Pleural metastases of sclerosing epithelioid fibrosarcoma].

Sclerosing epithelioid fibrosarcoma is a rare tumor recently described. The histological presentation can be confused with certain soft tissue benign tumors and certain sarcomas. Metastatic spread is usually late in the natural course of the disease. We report a case of recurrent sclerosing epithelioid fibrosarcoma with pleural metastases which developed ten years after surgical resection of the primary tumor. The tumor was formed by small uniform round epithelioid cells with a clear cytoplasm. The tumor cells were strongly positive for vimentin. This clinical case is discussed in light of other cases reported in the literature.

Aged↗

Postvaccinal sarcomas in the cat: epidemiology and electron probe microanalytical identification of aluminum.

An increase in fibrosarcomas in a biopsy population of cats in the Pennsylvania area appears to be related to the increased vaccination of cats following enactment of a mandatory rabies vaccination law. The majority of fibrosarcomas arose in sites routinely used by veterinarians for vaccination, and 42 of 198 tumors were surrounded by lymphocytes and macrophages containing foreign material identical to that previously described in postvaccinal inflammatory injection site reactions. Some of the vaccines used have aluminum-based adjuvants, and macrophages surrounding three tumors contained aluminum oxide identified by electron probe microanalysis and imaged by energy-filtered electron microscopy. Persistence of inflammatory and immunological reactions associated with aluminum may predispose the cat to a derangement of its fibrous connective tissue repair response, leading to neoplasia.

Aluminum↗

Association in the expression of Kirsten-ras oncogene and the major histocompatibility complex class I antigens in fibrosarcoma tumor cell variants exhibiting different metastatic capabilities.

The metastatic properties of the methylcholanthrene-induced T-10 sarcoma tumor variants which originated in C3H x C57Bl/6 F1 mice are correlated with the relative expression of class I major histocompatibility complex antigens. Both the nonmetastatic and the highly metastatic clones were found to lack the H-2K region-controlled H-2Kb and H-2Kk antigens. However, the nonmetastatic clones express only the H-2Db molecule whereas the metastatic clones express both the H-2Db and the H-2Dk molecules. Transfection of the highly metastatic lines with cloned H-2K genes (Kb, Kk) reduced their tumorigenicity and abolished the formation of metastasis in syngeneic mice, while the transfection of the nonmetastatic lines with cloned H-2Dk genes resulted in shifting the cells to the metastatic phenotype. The present study is aimed to investigate the expression of protooncogenes in the T-10 fibrosarcoma lines that exhibit distinct metastatic properties in correlation with the expressed H-2 antigens. The major oncogene which showed differential expression in the T-10 clones is Ki-ras. The amounts of specific Ki-ras messenger RNA and the Ki-ras Mr 21,000 protein are expressed in elevated levels in the H-2Dk-negative nonmetastatic clones in comparison with a low level of expression in the H-2Dk-positive highly metastatic clones. Expression of H-2K antigens following transfection with cloned H-2K genes had no effect on the expressed Ki-ras oncogene in the T-10 clones. However, transfection of the nonmetastatic cells with the cloned H-2Dk gene resulted in shifting of the cells to a highly metastatic phenotype and in reduction of the expressed c-Ki-ras oncogene.

Animals↗