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PubMed1993

Carcinosarcomas: current perspectives and an historical review of nosological concepts.

The origins of the concepts pertaining to the histogenesis of "carcinosarcomas" (CS) can be traced to theories that were advanced more than 100 years ago. Since that time, debate has continued over the clonality of these neoplasms and their corresponding lineages of differentiation. This article considers the historical aspects of CS and attempts to place these premises in a modern perspective. A review of current ultrastructural, cell-culture, and immunohistological data is used to support a monoclonal nature for carcinosarcoma, and to suggest that "sarcomatoid carcinoma" is a more apt designation for this tumor entity.

Adult↗

PubMed1993

Pulmonary carcinosarcoma: diagnostic approach by fine needle aspiration biopsy.

Carcinosarcoma of the lung is an exceedingly uncommon malignancy, possessing both malignant epithelial and mesenchymal elements. There are less than 100 cases reported in the English literature to date. Most of them were diagnosed by autopsy and surgery. Now we present a detailed report of a case with peripheral variant carcinosarcoma diagnosed by percutaneous needle biopsy under sonographic guidance. The clinical, pathologic and immunohistochemical hallmarks of this unique tumor are also reviewed.

Biopsy, Needle↗

PubMed1993

[Carcinosarcoma of the breast. Anatomic-clinical study of a case].

The authors report the case of a 66 year old woman, who underwent surgery for carcinosarcoma of the breast. This tumour consisted of an infiltrating ductal carcinoma intermingled with sarcomatous proliferation, resembling malignant fibrous histiocytoma, without evidence of any transition between the two. Carcinosarcomas of the breast are rare tumors. Their definition and their histogenesis are discussed in the literature. Their prognosis is worse than that of metaplastic carcinomas of the breast, particularly spindle cell carcinomas, justifying precise histological classification of these biphasic tumors.

Aged↗

PubMed1995

[True malignant mixed tumor of the parotid gland (carcinosarcoma)].

True malignant mixed tumor (carcinosarcoma) is a rare salivary gland tumor. In contrast to malignant mixed tumor, which means carcinoma ex pleomorphic adenoma in true malignant mixed tumor both carcinomatous and sarcomatous features are present in the same tumor. This report presents the case of a 43 year old man with a carcinosarcoma of the right parotid gland. Carcinomatous component was high grade ductal carcinoma. Mesenchymal component showed the features of giant cell type malignant fibrous histiocytoma. The diagnosis was supported by positive staining for cytokeratin in the carcinomatous part and positive vimentin, alpha-1-antitrypsin and CD 68 staining in the sarcomatous part of the tumor. Ultrastructural investigation confirmed the diagnosis. Multinucleated osteoclast type giant cells are probably of reactive origin.

Adult↗

PubMedDate not supplied

Carcinosarcoma of the liver with mesenchymal differentiation: a case report.

Carcinosarcoma of the liver with mesenchymal differentiation are very rare in adult patients. A case is reported with an exhaustive pathologic examination and review of the literature. A 61-year old man presented with general fatigue and dull abdominal pain. Two liver masses were diagnosed and resected by a right hepatectomy. Specimen pathology revealed that the tumor and lymph node consisted of two cancerous components. One carcinomatous component corresponding to a hepatocellular carcinoma and a sarcomatous component characterized by a diffuse proliferation of spindle shaped cells with chondrosarcomatous and osteosarcomatous changes. Patient died 9 months later of a diffusion of the tumor. For the first time, to our knowledge, a mesenchymal differentiation is demonstrated in liver carcinosarcoma.

Carcinoma, Hepatocellular↗

PubMed1995

Carcinosarcoma of the urinary bladder--case report and literature review.

We describe a patient who presented with gross haematuria and dysuria. Investigations confirmed a bladder tumour, for which transurethral resection was done. The histology showed a carcinosarcoma, which was muscle invasive but organ-confined. The patient refused radical surgery and underwent a course of radical radiotherapy. He died 14 months later. Carcinosarcoma of the urinary bladder is a rare, mixed malignant tumour, composed of mesenchymal and epithelial elements. It is commoner in elderly men. It is an aggressive tumour with a short clinical course, and must be distinguished from collision tumours and spindle cell tumours. Immunohistochemical stains are useful in its diagnosis. It is probably best managed by radical surgery with or without adjuvant therapy, but because of the small number of incidences reported, there is no universal agreement on its therapy.

Aged↗

PubMed1997

[Carcinosarcoma of the submaxillary gland].

Salivary gland carcinosarcoma is a rare neoplasm, with a poor prognosis, that should not be confused with the more common carcinoma ex-pleomorphic adenoma, in which the epithelial component alone is malignant. The authors report one case of carcinosarcoma of the submandibular gland, with no previous history of pre-existent tumor. The tumor exhibited two intermingled and very atypical cellular components, one undifferentiated and the other with a chondroid pattern. Immunostaining with epithelial markers in the undifferentiated area allowed to distinguish this tumor from salivary gland sarcomas. In addition, the positivity for EMA, vimentin, and S100 protein in the two predominant components suggested a common origin for the different tumoral cell types, and led to discuss the nomenclature and the still unclarified cellular origin of these tumors.

Aged↗

PubMed1996

[Lung carcinosarcoma--a report of 15 cases].

Lung carcinosarcoma is a rare pulmonary mixed malignant tumor. From November 1979 to Sept. 1992, among 4251 cases of pulmonary malignant tumor operated in our department 15 were lung carcinosarcoma (0.35%). Pneumonectomy was done in 6 patients, lobectomy in 8, thoacotomy in 1. Pathologically, squamous carcinoma with fibrosarcoma was observed in 4, squamous carcinoma with chondrosarcoma in 1, squamous carcinoma with pleomorphic sarcoma in 1, adenocarcinomma with fibrosarcoma in 7, adenocarcinoma with chondrosarcoma in 1, and small-cell carcinoma with chondrosarcoma in 1. There was no operation death. Upon follow up, the 1-, 3-, 5-, and 7-year survival rates were 66.7%, 53.3%, 42.9% and 2/7, respectively. The longest survival was 97 months. The histologica origin, the relationship between pathological findings and clinical features and the diagnosis, treatment and prognosis are discussed.

Adult↗

PubMed1997

[A rare biphasic pulmonary tumor, carcinosarcoma. A separate entity or differentiation variant of spindle-cell carcinoma?].

We report a case of pulmonary carcinosarcoma. Surgery is required for this rare mixed type, biphasic tumor. It is generally considered to be a malignant formation issuing from a single cell line but with a two-way differentiation into epithelial and conjunctive components. There is a differentiation continuum between spindle-cell carcinomas (also called monophasic sarcomatoid carcinoma) and carcinosarcoma (or biphasic sarcomatoid carcinoma) leading to debate concerning the immunohistochemical and ultrastructural features.

Carcinosarcoma↗

PubMed1998

[Bladder carcinosarcoma: chondrosarcoma plus urothelial carcinoma].

OBJECTIVE: To report an additional case of bladder carcinosarcoma. METHODS: An 87-year-old patient was admitted with a one-year history of gross hematuria. Ultrasound evaluation showed a bladder tumor and at cystoscopy a 4 x 3 cm polypoid, broad-based mass was found on the posterior wall of the bladder, surrounded by a multifocal papillary tumor. RESULTS: The tumor was resected transurethrally. Histologically, the tumor was composed of chondrosarcoma and urothelial sarcoma. Immunohistochemically, the sarcomatous elements stained strongly with vimentin and the carcinomatous cells were strongly positive for keratin. CONCLUSIONS: The foregoing findings support the view that these neoplasms are true carcinosarcomas.

Aged↗

PubMedDate not supplied

Carcinosarcoma of the esophagus: three cases with immunohistological examination.

Carcinosarcoma of the esophagus is a rare malignant tumor with both carcinomatous and sarcomatous components. We present 3 cases of carcinosarcoma of the esophagus and discuss the histogenesis of the tumors. We performed immunohistochemical studies using various antibodies: anti-cytokeratin, anti-vimentin, anti-smooth muscle actin, anti-p53, and MIB 1 reacting with Ki-67 nuclear antigen.

Biomarkers, Tumor↗

PubMed2000

Redundancy of lamellipodia in locomoting Walker carcinosarcoma cells.

Locomoting metazoan cells usually form lamellipodia at the leading front and it is widely accepted that lamellipodia are required for locomotion. In this case, suppression of lamellipodia must stop locomotion. However, the experiments show that lamellipodia are redundant for locomotion of Walker carcinosarcoma cells. Low latrunculin A concentrations (10(-7) M) transform polarised locomoting cells with lamellipodia into cells without morphologically recognisable protrusions showing an increased speed of locomotion and a reduced amount of cellular F-actin. Whereas untreated cells show a fairly linear distribution of F-actin along the plasma membrane, cells lacking morphologically recognizable protrusions at the front show modifications at the front consisting in an irregular distribution of F-actin with formation of small or large patches of F-actin alternating with small or large gaps in the F-actin layer. This is associated with a reduced resistance to deformation pressure at the front of the cell. High concentrations of latrunculin A (>10(-7) M) compromising contraction at the rear stop locomotion, suggesting that cortical contraction is important for locomotion to occur in these cells. The results are consistent with the view that actin polymerization is important for formation of lamellipodia but they are not compatible with the view that lamellipodia are essential for locomotion of Walker carcinosarcoma cells. A unifying hypothesis for the formation of different types of protrusions is proposed.

Actins↗

PubMed2001

The Rho/Rho-kinase and the phosphatidylinositol 3-kinase pathways are essential for spontaneous locomotion of Walker 256 carcinosarcoma cells.

Signal transduction pathways controlling spontaneous locomotion of Walker carcinosarcoma cells are not well understood. We have therefore investigated the role of signalling proteins in development of polarity and locomotion of these cells. Treatment of the cells with 100 ng/ml pertussis toxin had no significant effect on the percentage of polarized cells. In contrast, 2 different phosphatidylinositol 3-kinase inhibitors (wortmannin and LY-294002) markedly reduced the proportion of polarized cells. Spontaneous locomotion of the cells was also significantly inhibited by these two inhibitors. In agreement with these data, we observed localization of the p85alpha subunit of phosphatidylinositol 3-kinase predominantly in the membrane fraction of Walker carcinosarcoma cells, indicating constitutive activation of this enzyme. We also investigated a role of Rho family proteins. Spontaneous development of polarity was almost completely suppressed by electroporation of the cells in the presence of 4 microg/ml C(3) exoenzyme, which specifically ADP-ribosylates and inactivates Rho. Two downstream targets of Rho, the Rho-activated kinases I and II, were also detected predominantly in the particulate membrane fraction, suggesting constitutive activation. A specific Rho-kinase inhibitor (Y-27632) blocked spontaneous polarization and migration in a concentration-dependent manner. Our results indicate that constitutive activation of the Rho/Rho-kinase pathway and of phosphatidylinositol 3-kinase plays an essential part in spontaneous development of polarity and cell locomotion of these cells.

Androstadienes↗

PubMed1985

Phorbol myristate acetate (PMA) suppresses polarization and locomotion and alters F-actin content of Walker carcinosarcoma cells.

This study demonstrates a novel feature of PMA, its ability to suppress chemokinetic polarization and locomotion of tumor cells. Walker carcinosarcoma cells exhibit two distinct types of polarization and locomotion, i.e. spontaneous polarization characterized by ruffles at the front and stimulated polarization and locomotion in response to the microtubule-disassembling agents colchicine, vinblastine and nocodazole, which are characterized by blebbing at the front. The tumor promotor phorbol myristate acetate (PMA), but not phorbol, was found to suppress both types of polarization and random locomotion at concentrations between 10(-8) and 10(-6)M. The effect of 10(-6)M PMA was virtually complete within 5 min. Inhibition of locomotion was due to both a reduction in the speed of migrating cells and the proportion of migrating cells. Changes in shape and chemokinesis of Walker carcinosarcoma cells were associated with alterations in the relative amount and the topographical distribution of F-actin as determined by NBD-phallacidin binding. Suppression by PMA was associated with loss of the polar topographical distribution of F-actin visualized by NBD-phallacidin binding. In the presence of PMA, the relative amount of F-actin was higher than in unstimulated controls and lower in cells exposed to microtubule-disassembling agents.

Actin Cytoskeleton↗

PubMed1980

Therapy of solid Walker carcinosarcoma 256 with bleomycin after synchronization with hydroxyurea.

Rats with the solid Walker carcinosarcoma 256 were synchronized with hydroxyurea (6 x 50 mg/kg or 1 x 300 mg/kg body weight) and treated with bleomycin (32 mg/kg body weight) at different time points thereafter. Bleomycin clearly affects Walker carcinosarcoma cells at the G1/S boundary or in S-phase. The improvement in the results of bleomycin therapy after pretreatment with hydroxyurea can mainly be accounted for by the synchronization of the tumour cells.

Animals↗

PubMed2006

Effect of immunisation with cancer procoagulant on the growth of Walker 256 carcinosarcoma cells in rats.

The effect of preimmunisation with cancer procoagulant (CP) on the growth of Walker 256 carcinosarcoma cells in Wistar Lew/Han/IMP rats in vivo has been analysed. One group of rats was immunised with CP purified from human amnion-chorion membranes. The rest of the animals (control groups) were injected with 0.9% NaCl in Freund's adjuvant or were not immunised at all. When the presence of polyclonal anti-CP antibody was detected in CP-immunised rats' serum, all (CP-immunised and control) animals were injected i.p. with 4.8 x 10(5) Walker 256 cells per rat. After 5 days ascitic fluid was collected and viable cells were counted. The complete lack of viable Walker 256 carcinosarcoma cells in 24% of the CP-immunised rats was observed. However, the viable neoplastic cells were present in all control (NaCl-injected and nonimmunised) animals. It seems possible that CP plays an important role in tumour progression, so immunisation with CP can reduce the risk of development of malignant disease.

Animals↗

PubMed1980

Structural comparison of human, bovine, rat, and Walker 256 carcinosarcoma asparaginyl-tRNA.

The complete nucleotide sequences of human placenta, human liver, and bovine liver tRNAAsn have been determined. A comparison of these tRNA structures with the previously reported nucleotide sequences of rat liver and Walker 256 carcinosarcoma tRNAAns reveals that the primary nucleotide sequences of the major species of mammalian cytoplasmic tRNAasn are conserved in higher eucaryotes. The complete nucleotide sequence of these tRNAs is: pG-U-C-U-C-U-G-U-m1G-m2G-C-G-C-A-A-D-C-G-G-D-X-A-G-C-G-C-m2(2)G-psi-psi-C-G-G-C-U-Q(G)-U-U-t6A-A-C-C-G-A-A-A-G-m7G-D-U-G-G-U-G-G-Z-psi-C-G-m1A-G-C-C-C-A-C-C-C-A-G-G-G-A-C-G-C-C-AOH where X is 3-(3-amino-3-carboxyl-n-propyl)uridine, Q is 7-(4,5-cis-dihydroxyl-1-cyclopenten-3-yl-aminomethyl)-7-deazaguanosine, Z is an unknown modified nucleotide, and Q(G) represents the replacement of Q nucleoside by G nucleoside in Walker 256 carcinosarcoma tRNAAsn. These primary structures were determined by combined use of the 3H- and 32P-post-labeling techniques. Sequences were compared by tritium nucleoside trialcohol analysis, completed RNAase T1 digestion followed by 3H-labeled fingerprinting on polyethylenimine-impregnated cellulose by two-dimensional thin-layer chromatography (TLC), and polyacrylamide gel electrophoresis of either 5'-32P- and/or 3'-[32P]pCp-labeled tRNA after partial ribonuclease digestions.

Animals↗

PubMed2005

Role of Rho, Rac, and Rho-kinase in phosphorylation of myosin light chain, development of polarity, and spontaneous migration of Walker 256 carcinosarcoma cells.

As previously shown, constitutive activation of the small GTPase Rho and its downstream target Rho-kinase is crucial for spontaneous migration of Walker carcinosarcoma cells. We now show that after treatment of cells with either the Rho inhibitor C3 exoenzyme or the Rho-kinase inhibitor Y-27632, constitutive myosin light chain (MLC) phosphorylation is significantly decreased, correlating with inhibition of cell polarization and migration. Transfection with a dominant-negative Rho-kinase mutant similarly inhibits cell polarization and MLC phosphorylation. Transfection with a dominant-active Rho-kinase mutant leads to significantly increased MLC phosphorylation, membrane blebbing, and inhibition of cell polarization. This Rho-kinase-induced membrane blebbing can be inhibited by Y-27632, ML-7, and blebbistatin. Unexpectedly, overactivation of RhoA has similar effects as its inhibition. Introduction of a bacterially expressed constitutively activated mutant protein (but not of wild-type RhoA) into the cells or transfection of cells with a constitutively active RhoA mutant both inhibit polarization and decrease MLC phosphorylation. Transfection of cells with constitutively active or dominant-negative Rac both abrogate polarity, and the latter inhibits MLC phosphorylation. Our findings suggest an important role of Rac, Rho/Rho-kinase, and MLCK in controlling myosin activity in Walker carcinosarcoma cells and show that an appropriate level of RhoA, Rac, and Rho-kinase activity is required to regulate cell polarity and migration.

Animals↗