A case of circumscribed myosarcoma of the prostate.
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One of the two isoforms of the human insulin receptor (isoform A or IR-A) binds IGF-II with high affinity and is predominantly expressed in fetal tissues and malignant cells. We evaluated the biological relevance of IR-A in human myosarcoma cells. Six myosarcoma cell lines were studied. All produced high amounts of IGF-II and five of them predominantly expressed IR-A. SKUT-1 leiomyosarcoma cells, that do not express the IGF-IR, were identified as a suitable model to study the effects of IR-A in the absence of the interference of IGF-IR. In these cells, which express high levels of IR with an IR-A relative abundance of approximately 95%, IGF-II elicits biological effects exclusively via IR-A activation and IGF-I is almost ineffective. Blockade of autocrine IGF-II reduced unstimulated cell viability and migration. Although both insulin and IGF-II activate IR-A, these two ligands showed a different ability to activate different intracellular signaling pathways and to elicit different biological effects. Insulin was more potent than IGF-II in activating the PI3-K/Akt pathway and in protecting cells from apoptosis. In contrast, IGF-II was more potent than insulin in activating the Shc/ERK pathway and in stimulating cell migration. These data indicate that IGF-II sensitive IR-A is the predominant IR isoform in a variety of myosarcoma cells. In SKUT-1 leiomyoma cells this fetal IR isoform may vicariate the IGF-IR for cell response to both insulin and IGF-II. Acting on the same IR-A receptor IGF-II is more potent than insulin in stimulating cancer cell migration.
Twenty-one forequarter amputations were performed at our institute during a 15 year period for soft tissue sarcoma, osteosarcoma, recurrent malignant melanoma and epidermoid carcinoma. Two patients in this group who have had recurrent carcinoma of the breast with a painful, edematous and ulcerated upper extremity were palliated and had significant relief. The over-all five year survival rate following this procedure for curative intent was 25 per cent. There were no five year survivors of unclassified sarcoma, myosarcoma and recurrent malignant melanoma. Thus, we do not recommend this procedure for recurrent malignant melanoma, although it can be performed as a palliative measure. Since most of the patients with malignant bone tumors, unclassified sarcoma and myosarcoma have systemic metastasis develop within two to eight months after this procedure, new methods should be explored to detect early metastasis before undertaking this psychologically traumatic procedure. Adjuvant chemotherapy and other modalities of adjuvant therapies are recommended in this group with poor prognosis. A local recurrence after this amputation in patients with unclassified lesions and myosarcoma should be considered as an indication of systemic metastasis.
With the aim of identifying objective cytogenetic-morphologic correlations, we evaluated 46 pleomorphic soft tissue sarcomas (mainly diagnosed originally as malignant fibrous histiocytomas) with clonal chromosome aberrations both cytogenetically and morphologically as part of an international collaborative study. By detailed histopathologic examination, most cases could be categorized into specific tumor types. Eight sarcomas were diagnosed as lipogenic (4 pleomorphic, 1 combined pleomorphic and myxoid/round cell, and 3 dedifferentiated liposarcomas), 19 as myogenic [11 leiomyosarcomas, 1 rhabdomyosarcoma, 4 myosarcomas not otherwise specified (NOS), and 3 probable myosarcomas NOS], 8 as myxofibrosarcomas, 1 as a malignant peripheral nerve sheath tumor, 1 as malignant mesenchymoma, 1 as extraskeletal osteosarcoma, I as sarcoma resembling proliferative fasciitis, and 7 as pleomorphic sarcomas NOS. In a three-grade system, 10 tumors were grade 2 and 36 were grade 3. The majority had highly complex karyotypes. A total of 24 recurrent abnormalities (defined by their presence in at least five cases) were detected: ring chromosomes, homogeneously staining regions (hsr) and/or double minute chromosomes (dmin), and structural rearrangement of 22 different chromosome bands or regions. The frequency and distribution of the recurrent karyotypic features were uneven. Grade 3 tumors displayed, on average, more aberrations per case than did grade 2 tumors. Nine of the selected abnormalities, including hsr/dmin and rearrangements of 19p13 and 19q13, were found only among the high-grade tumors. When the tumors were subdivided according to lineage of differentiation, the highest frequency of aberrations was seen in pleomorphic sarcomas NOS, followed by myxofibrosarcomas, myogenic sarcomas, and lipogenic sarcomas. None of the selected rearrangements was, however, specific for any of these subgroups. The sole consistent cytogenetic-morphologic association was that all three dedifferentiated liposarcomas had multiple abnormal clones, at least one of which contained supernumerary ring chromosomes. Due mainly to karyotype complexity, it therefore seems unlikely that cytogenetic analysis can assist in the differential diagnostic subclassification of pleomorphic sarcomas, nor was there any clear-cut indication that the karyotypic picture could be used to predict clinical outcome. Although the mean number of recurrent chromosome aberrations was almost twice as high in sarcomas that gave rise to metastases as among those that did not, no particular aberration was restricted to either of the two subgroups.
Numerous reports document the existence of autoantibodies to MUC1 in the circulation of individuals with breast and other solid malignancies, with the majority of researchers utilizing MUC1 peptides in their detection. This report documents the purification, using peptide and whole molecule, and characterization of such autoantibodies from an individual with an unusual, highly MUC1-positive, myosarcoma. Purification of autoantibodies from serum was performed using affinity chromatography against either MUC1 peptide or whole molecule MUC1 [derived both from the patient (Pt-MUC1) and from a pool of sera from patients with advanced breast cancer (ABC-MUC1)]. Enzyme-linked immunosorbent assays (ELISAs) were used to compare specificity of purified autoantibodies. Peptide epitopes were determined by Ptifcan system against 7-mer peptides covering the 20 amino acid repeat of the MUC1 extracellular domain. Substantially higher amounts of autoantibodies were isolated when purifying against Pt-MUC1 rather than either ABC-MUC1 or peptide. Whole molecule purified autoantibodies demonstrated an increased specificity for tumour-derived MUC1. Pt-MUC1 autoantibodies were of both the immunoglobulin (Ig)G and IgM class, whilst autoantibodies purified against ABC-MUC1 and MUC1 peptide were IgG only. A greater range of peptide epitopes was defined by those autoantibodies purified against whole molecule. This report presents data indicating the presence of autoantibodies to MUC1 in an individual diagnosed with a MUC1 over-expressing myosarcoma. Confirmation of these autoantibodies as being specific for tumour-associated MUC1 is given. Further, it suggests that, although autoantibodies are present that recognize core protein determinants, the initial, and dominant, immunizing epitope is not purely pretentious in nature.
Human myosarcomas, liposarcomas, meningosarcomas, glioblastomas and malignant schwannomas, their benign counterparts and normal cells from which these tumours derive, were examined for the expression of beta 2-microglobulin (beta 2m). Formalin fixed specimens from these tumours were studied by light microscopy employing the immunoperoxidase method with the use of antibodies directed towards beta 2m. The malignant tumours showed a broad spectrum from unstained to strongly stained tumours, most pronounced among myosarcomas. In addition, most stained tumours displayed a mosaic staining pattern in that unstained areas alternated with stained. There was a tendency towards increased staining for beta 2m in malignant compared to normal cells; this was also observed in the benign tumours although to a lesser degree. The results differ from most earlier studies, mainly of carcinomas which have shown a tendency towards down-regulation of MHC I molecules on the tumour cells. The results are discussed in relation to concepts of immune surveillance of tumours.
Various types of human gynecological cultured tumor cells were tested for the sensitivity to Peplomycin (PEP), an effective antitumor antibiotic for squamous cell carcinomas, by the regrowth assay method together with morphological observation. Bleomycin-hydrolase activity of these cell lines was also compared in cell-free extracts by assaying the conversion of Bleomycin into its deamidated from (HPLC method). SKG-I, SKG-II, SKG-IIIb cells derived from squamous cell carcinoma of the cervix and RKN cells derived from myosarcoma of the ovary were much more sensitive to PEP than other cell lines. PEP was found to be mainly a time-dependent drug, but also concentration dependent. The effect of PEP on cell morphology was characterized by the appearance of enlarged cells and swelling nuclei. The specific activities of Bleomycin-hydrolase in SKG-I, SKG-II, SKG-IIIb cells were shown to be relatively lower than that in other cell lines. These results suggested that cervical squamous carcinoma cells and ovarian myosarcoma cells were sensitive to PEP and Bleomycin-hydrolase activity was one of factors which decided the PEP sensitivity of human cultured tumor cells.
A modification of the Hedley-method for flow cytometric DNA analysis of paraffin-embedded tissues is presented. Dewaxed and dehydrated tissue from paraffin blocks was incubated with subtilisin Carlsberg (pronase, Sigma protease XXIV) and then stained directly without washing and centrifugation. The loss of material was minimized, which was advantageous, for example, for the analysis of core-biopsies, and all measured samples showed extremely low frequencies of clumped cell nuclei. This made is easier to detect polyploid nuclei and even rare nuclei of high ploidy could be identified. S-phase analyses were more precise, since the background originating from clumped debris particles was very low. The improved method was applied to the estimation of frequencies of high-polyploid nuclei found in various diploid, tetraploid, and aneuploid human myosarcomas of the uterus.
The cytotoxic effect of bleomycin and peplomycin was compared using a methylcellulose monolayer assay for the cultivation of human tumor cells. In 3 out of 4 samples from human malignant melanomas peplomycin proved to be more cytotoxic than bleomycin. Peplomycin was more cytotoxic than bleomycin in 1 of 5 myosarcoma samples, whereas 2 samples from squamous cell carcinomas of the lung showed identical dose response curves. In 1 carcinoma of the gall bladder peplomycin was more toxic than bleomycin.
PURPOSE: Retrorectal tumors are rare entities often found in females during reproductive age. Reports of retrorectal tumors complicating pregnancy are scant. This study presents two cases of retrorectal tumors complicating pregnancy and a literature review. METHODS: Two patients bearing retrorectal tumors diagnosed during pregnancy were referred to our care at the postpartum period. Both then underwent exploratory laparotomy. RESULTS: One patient had premature delivery by cesarean section because of hemorrhage from abruptio placentae followed by fetal mortality. Attempts to resect the tumor immediately after delivery had been unfruitful. The tumor was also unresectable on exploratory laparotomy. Biopsy studies of the tumor were consistent with low-grade myosarcoma. Another patient had a benign cystic mass that had been conservatively monitored throughout pregnancy. A healthy baby was delivered at term by cesarean section. The cyst was later resected via Kraske's incision and was diagnosed as cystic teratoma. CONCLUSIONS: Retrorectal tumors may cause significant local effects such as complicated pregnancy. Early detection in the population at risk is needed, as correct diagnosis and treatment may be done only on surgical exploration. During pregnancy, careful monitoring of advanced tumors is mandatory and may be sufficient to prevent maternal and fetal complications.
On the basis of 41 personally observed cases from 1957 to 1974 and 435 case reports in the literature from 1957 to 1972, a scale of malignancy of the histological forms of primary pulmonary sarcomas is presented. A fairly continuous rise in the rate of malignancy according to the differentiation of the tissues can be convincingly recognized. The more mature a pulmonary sarcoma is, the better is the postoperative prognosis. The rate of malignancy increases from the relatively differentiated and tissue matured fibrosarcomas over the spindle cell sarcomas and round cell sarcomas, to the completely non-differentiated polymorph cell sarcomas. Primary myosarcomas, neurosarcomas and reticulum sarcomas of the lungs take an isolated position within this scale of malignancy. Primary lymphosarcomas are the most common and have clearly the best postoperative prognosis. The greatest malignancy is found with the carcinosarcomas. The characteristics of each of the histomorphological forms of primary sarcoma of the lungs are discussed. At the same time it is shown that the postoperative prognosis of endothoracal sarcomas is determined not only by their histological structure, but also by their localization in the lungs, mediastinum, or chest wall. Forty-one primary pulmonary sarcomas were compared with 22 sarcomas of the mediastinum and 17 sarcomas of the chest wall. Due to their long period of development, with rare symptoms and late diagnosis, sarcomas of the lungs and the mediastinum have a similar postoperative prognosis, in contrast to the endothoracal sarcomas of the chest wall which have a clearly more favourable prognosis.
The existence of a tumor necrosis factor (TNF) receptor on KYM human myosarcoma cells was elucidated by Scatchard plot and cross-linking analysis. The average number of specific binding sites per cell was 15,300 and the apparent dissociation constant Kd was 4.0 X 10(-10) M. The estimated relative molecular mass of a TNF receptor on KYM cell was approximately 95,000.
Results from radiotherapeutic treatment of 200 patients with malignant tumors of the esophagus are reported. The principal part is represented by squamous cell carcinomas with 88%, followed by adenocarcinomas with 4.5%, by more or less differentiated solid carcinomas with 4%, and small cell carcinomas with 1.5%. Sarcoma was found in three cases, one of them a myosarcoma, another a reticulosarcoma. An ectopic carcinoma of the gastric glands was present in one case. The staging was performed according to the TNM system. A focal dose of 6000 to 6500 rd within 6 or 8 weeks was tried for, using 60Co-gamma-rays. The one-year and five-year survival rates in stage T2N0M0 amounted to 80% and to 17%; no survival was obtained in stage T3N0M0. Out of the total of stage T2-3N0M0 cases 24% obtained one-year survival, and 2% five-year survival. In stages T3N2-3M0 and T3Nx-3M1 after one year 9% and 7% of the patients were alive. The mean survival time of stage T2N0M0 cases was 30.5 months; of T3N0M0, 7.3 months; of T3N1-3M0, 5.2 months; of T3Nx-3M1, 3.8 months. The one-year and five-year survival rates, being related to the irradiation dose administered, amounted to 28% and to 2% after a minimum dose of 5000 rd to the focus. With less than 5000 rd, none of the patients survived two years. The bad results of treatment demand new therapeutic pathways. Short-term pre-irradiation followed by surgical treatment is discussed as well as a combined radiation therapy with cobalt-60 and neutrons or a combined radio-chemotherapy using cytostatics.