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PubMed1998

Diagnosis of pulmonary Kaposi's sarcoma by detection of human herpes virus 8 in bronchoalveolar lavage.

Human herpes virus 8 (HHV8) DNA has recently been detected in sarcoma tissue of patients with Kaposi's sarcoma. HHV8 DNA could also be found in bronchoalveolar lavage (BAL) fluid of patients with tracheobronchial Kaposi's sarcoma. To determine the specificity, sensitivity and predictive values of HHV8 DNA detection in the BAL for the diagnosis of pulmonary Kaposi's sarcoma, 100 consecutive BAL were prospectively analyzed for the presence of HHV8 DNA using a nested PCR assay. In addition, 19 BAL samples of 14 AIDS patients with cutaneous or visceral Kaposi's sarcoma were retrospectively investigated. The prospective group consisted of 79 BAL performed in immunocompromised and of 21 BAL in nonimmunocompromised patients. Four patients of the prospectively analyzed group undergoing six BAL showed tracheobronchial Kaposi's sarcoma at five bronchoscopies. All of the five BAL samples performed in these patients with endoscopically visible Kaposi's sarcoma were positive for HHV8 DNA. Following chemotherapy and antiretroviral treatment tracheobronchial Kaposi's sarcoma was no longer detectable at a subsequent bronchoscopy and HHV8 DNA in BAL became negative in one patient. One BAL sample of a HIV-positive patient with no evidence of Kaposi's sarcoma was HHV8 DNA-positive. The sensitivity, specificity, positive and negative predictive values of HHV8 detection for the diagnosis of tracheobronchial Kaposi's sarcoma were 100%, 98.9%, 83.3%, and 100%, respectively. Twelve of 19 BAL samples of the retrospective group were HHV8 DNA-positive. In this group, 10 patients undergoing a total of 14 BAL suffered from pulmonary Kaposi's sarcoma. HHV8 DNA was documented in 10 of these 14 BAL samples. In three BAL of this group HHV8 DNA was positive, but pulmonary Kaposi's sarcoma was diagnosed at a later stage. In conclusion, the detection of HHV8 DNA in BAL is restricted to patients with Kaposi's sarcoma and is highly sensitive and specific for pulmonary involvement of Kaposi's sarcoma.

Adult↗
PubMedDate not supplied

Sarcoma and thyroid disorders: a common etiology?

We have recently observed that many of our sarcoma patients presented also with thyroid disorders. Literature data are almost unavailable on this topic. The relationship between the sarcoma and thyroid disorders is examined. Retrospective analysis of files of patients with sarcoma and clinically overt thyroid disorders was carried out. Of the 375 patients with soft tissue sarcomas (STS) and 235 with bone sarcoma (BS) including small blue round cell tumors (SBRC), 28 patients (4.6%) had an associated significant thyroid disorder. The types of sarcoma were mainly liposarcoma followed by malignant fibrous histiocytoma, leiomyosarcoma and bone sarcoma. The primary sites were mainly limb and trunk. The interval between the diagnosis of the thyroid disorder and the sarcoma varied between -14 years (thyroid first) and +16.5 years (thyroid later) with a median of -0.2 years. Thyroid disorders included goiter, thyroiditis and carcinoma. There are both basic-science and clinical evidence to a possible common pathway that leads to the association between overt thyroid disorders and sarcomas of bone or soft tissues. Oncogene erbA activity is related to thyroid receptors to T3 and to development of sarcoma. Cross talk of the sarcoma oncogene and the erbA might contribute to the development of sarcoma. The thyroid hormone receptor and the highly related viral oncoprotein v-erbA are found exclusively in the nucleus as stable constituents of chromatin. It has been shown that v-erbA can block the spontaneous differentiation in erythroid cells transformed by various retroviral oncogenes. V-erbA can alter the spectrum of neoplasia induced by the v-src oncogene, which causes predominantly sarcomas and erythroblastosis in chicks. The erbA can cooperate with other oncogenes such as v-erbB or with v-fms, v-ras, and c-kit. Cooperation with v-myc may play a role in the development of rhabdomyosarcoma especially in thyroid hormone deficiency state. The possible clinical implications are the need to screen patients with sarcoma to thyroid disorders, and patients with thyroid disorders for malignant diseases.

Adult↗
PubMed1994

Post-treatment sarcoma in breast cancer patients.

BACKGROUND: Many patients treated for breast cancer with radiotherapy will survive their disease and be at risk for treatment-related sarcoma for many years. METHODS: In order to identify patients with post-treatment sarcoma and define this disease, we examined the records of 99 patients treated for sarcoma with a history of antecedent breast carcinoma. Of these patients, 51 were felt to have a sarcoma unrelated to breast cancer treatment and 48 were felt to have a treatment-related sarcoma (secondary to lymphedema and/or radiation). RESULTS: Lymphangiosarcoma of the extremity was the most common histologic subtype of post-treatment sarcoma, accounting for 22 of 48 cases (46%). Twenty-six patients (54%) developed nonlymphangiosarcoma post-treatment sarcoma; all of these were radiation-associated sarcomas. The median latency interval between the diagnosis of breast cancer and the development of sarcoma was 11 years (range 4-44) and was not different between the two groups. However, patients with nonlymphangiosarcoma were significantly younger when diagnosed with breast cancer than were those with lymphangiosarcoma of the extremity (median 43 vs. 51 years, p < 0.001). The survival of all 48 patients was poor: 5-year survival was 29%. Five-year survival of patients with other types of post-treatment sarcoma was just as poor as those with lymphangiosarcoma of the extremity (30% vs. 28%, p = 0.98). CONCLUSIONS: Patients who develop sarcoma after treatment for breast cancer have a poor prognosis whether it occurs as Stewart-Treves syndrome or other types of post-treatment sarcoma. Younger patients may be at higher risk than are older patients for the development of nonlymphangiosarcoma post-treatment sarcoma.

Adult↗
PubMed2004

SYT-SSX fusion genes in synovial sarcoma of the thorax.

Synovial sarcoma (SS) is characterized by a chromosomal translocation resulting in the expression of an SYT-SSX chimeric transcript, usually SYT-SSX1 or SYT-SSX2. Synovial sarcoma typically originates in the limbs, and its location in the thorax is rare. Synovial sarcomas are usually classified into three histologic subtypes: biphasic, monophasic and poorly differentiated tumors. The detection of the characteristic chimeric transcript often contributes to a histopathological diagnosis, especially when the tumor arises in an unusual location. Previous studies have shown that SYT-SSX1 is the most common SYT-SSX fusion transcript in biphasic synovial sarcomas of the limbs. Here, we report two cases of synovial sarcoma originating in the thorax. The presence of SYT-SSX2 chimeric transcripts was confirmed by reverse transcript polymerase chain reaction (RT-PCR) and a direct sequencing analysis in both cases. The tumor in case 1 originated from the pericardium, which is an exceedingly rare site for primary synovial sarcoma; only three other cases of synovial sarcoma originating in the pericardium have been previously reported. Case 2 exhibited a biphasic synovial sarcoma of the mediastinum containing an SYT-SSX2 fusion transcript, which is a rare fusion type in biphasic synovial sarcomas of the limbs. We reviewed previous reports of thoracic synovial sarcomas containing an analysis of the SYT-SSX fusion transcript and found that case 2 in the present study was the first description of a biphasic synovial sarcoma of the thorax with an SYT-SSX2 fusion transcript. However, the number of reported cases was not sufficient to conclude that SYT-SSX2 fusion in biphasic synovial sarcoma of the thorax is, indeed, rare. Further genetic analysis is needed to fully understand the biological and clinical features of synovial sarcoma originating in the thorax.

Adolescent↗
PubMed2002

Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation.

Synovial sarcoma is an aggressive spindle cell sarcoma with two major histological subtypes, biphasic and monophasic, defined respectively by the presence or absence of areas of glandular epithelial differentiation. It is characterized by a specific chromosomal translocation, t(X;18)(p11.2;q11.2), which juxtaposes the SYT gene on chromosome 18 to either the SSX1 or the SSX2 gene on chromosome X. The chimeric SYT-SSX products are thought to function as transcriptional proteins that deregulate gene expression, thereby providing a putative oncogenic stimulus. We investigated the pattern of gene expression in synovial sarcoma using cDNA microarrays containing 6548 sequence-verified human cDNAs. A tissue microarray containing 37 synovial sarcoma samples verified to bear the SYT-SSX fusion was constructed for complementary analyses. Gene expression analyses were performed on individual tumor samples; 14 synovial sarcomas, 4 malignant fibrous histiocytomas, and 1 fibrosarcoma. Statistical analysis showed a distinct expression profile for the group of synovial sarcomas as compared to the other soft tissue sarcomas, which included variably high expression of ERBB2, IGFBP2, and IGF2 in the synovial sarcomas. Immunohistochemical analysis of protein expression in tissue microarrays of 37 synovial sarcomas demonstrated strong expression of ERBB2 and IGFBP2 in the glandular epithelial component of biphasic tumors and in solid epithelioid areas of some monophasic tumors. Fluorescence in situ hybridization analysis indicated that the ERBB2 overexpression was not because of gene amplification. Differentially expressed genes were also found in a comparison of the expression profiles of the biphasic and monophasic histological subgroups of synovial sarcoma, notably several keratin genes, and ELF3, an epithelial-specific transcription factor gene. Finally, we also noted differential overexpression of several neural- or neuroectodermal-associated genes in synovial sarcomas relative to the comparison sarcoma group, including OLFM1, TLE2, CNTNAP1, and DRPLA. Our high-throughput studies of gene expression patterns, complemented by tissue microarray studies, confirm the distinctive expression profile of synovial sarcoma, provide leads for the study of glandular morphogenesis in this tumor, and identify a new potential therapeutic target, ERBB2, in a subset of cases.

Cell Differentiation↗
PubMed2004

Aberrant expression of tight junction-related proteins ZO-1, claudin-1 and occludin in synovial sarcoma: an immunohistochemical study with ultrastructural correlation.

Synovial sarcoma demonstrates epithelial differentiation, either by light microscopy (biphasic synovial sarcoma) or by immunohistochemical/ultrastructural methods only (monophasic) and poorly differentiated synovial sarcoma. Although the glands of synovial sarcoma are known to have tight junction-like structures, far less is known about junction formation in the spindled component of synovial sarcomas. Additionally, it is unknown whether the tight junctions of synovial sarcoma are normally constituted. The tight junction is a multiprotein complex consisting of numerous proteins that include ZO-1, claudin-1 and occludin. A total of 35 cases of synovial sarcoma (13 biphasic, 14 monophasic and eight poorly differentiated) were immunostained for ZO-1, claudin-1 and occludin using commercially available antibodies, heat-induced epitope retrieval and standard avidin-biotin technique. When available, corresponding electron micrographs were reviewed. For five cases, the presence of either an SYT-SSX1 (three cases) or SYT-SSX2 (two cases) gene fusion was known. Positive cases showed particulate membrane staining. The glands of biphasic synovial sarcomas expressed ZO-1 (13/13), claudin-1 (12/13) and occludin (11/13) in a manner identical to normal glandular epithelia, at the apical portion of the lateral membrane. The spindle cells of biphasic synovial sarcomas showed abnormal circumferential membranous expression of ZO-1 (12/13), claudin-1 (6/13) and occludin (3/13). Monophasic synovial sarcomas expressed ZO-1 in a circumferential pattern (13/14) but less often claudin-1 (4/14) or occludin (3/14). Poorly differentiated synovial sarcomas expressed ZO-1 (8/8) and claudin-1 (6/8) but only rarely occludin (2/8). By electron microscopy, recognizable tight junctions were seen only in glands. No correlation was seen between histologic subtype or fusion type and expression of tight junction proteins. We conclude that the glands of biphasic synovial sarcomas show well-organized, true epithelial tight junctions. In contrast, the spindled cells of all synovial sarcomas show significant abnormalities in the expression and localization of tight junction proteins, suggesting partial and/or aberrant epithelial differentiation.

Claudin-1↗
PubMed2005

Latency-associated nuclear antigen expression and human herpesvirus-8 polymerase chain reaction in the evaluation of Kaposi sarcoma and other vascular tumors in HIV-positive patients.

Human herpesvirus-8 (HHV-8) latency-associated nuclear antigen (LANA) is expressed in endothelial and spindle cells of nearly all Kaposi sarcomas, and the presence of this antigen in serum is strongly correlated with the risk of developing Kaposi sarcoma in immunocompromised individuals. Studies of vascular tumors occurring in the general population show LANA expression to be specific for Kaposi sarcoma. No study to date, however, has examined whether non-Kaposi sarcoma vascular tumors arising in immunocompromised patients may express LANA, possibly reflecting origin from an HHV-8-infected endothelial progenitor cell. The objective of this study was to evaluate the specificity of LANA expression for Kaposi sarcoma in immunocompromised patients by LANA immunohistochemistry and real-time polymerase chain reaction (PCR) for HHV-8. A total of 13 cases of non-Kaposi sarcoma vascular tumors (12 hemangiomas and one epithelioid hemangioendothelioma) and 24 cases of Kaposi sarcoma, all from known HIV-positive patients, were immunostained for LANA and evaluated for the presence of HHV-8 DNA by real-time PCR. LANA expression was seen in 22 of 24 (92%) of Kaposi sarcoma cases and in 0 of 13 non-Kaposi sarcoma cases. Real-time PCR detected HHV-8 in all of the Kaposi sarcoma cases and in four of the non-Kaposi sarcoma cases (all hemangiomas). LANA expression appears to be a highly sensitive and specific marker of Kaposi sarcoma in both the general population and in HIV-positive patients. This is in contrast to HHV-8 PCR, which is positive in a small subset of non-Kaposi sarcoma vascular tumors, most likely due to detection of HHV-8 within intratumoral blood mononuclear cells by the highly sensitive real-time PCR technique. For this reason, LANA immunohistochemistry is preferable to HHV-8 PCR for the evaluation of problematic vascular proliferations in HIV-positive individuals.

Adult↗
PubMed2002

Validity and reproducibility of histologic diagnosis and grading for adult soft-tissue sarcomas.

Soft-tissue sarcomas in adults show great variations in histologic type and grade. A valid and reproducible prognostication system is needed to select patients with soft-tissue sarcomas who could benefit from adjuvant chemotherapy. This study was conducted to assess the validity and reproducibility of diagnosis of the histologic type, MIB-1 grade, and mitosis grade, as well as of the 3 components of these grading systems. MIB-1 grade is a recently proposed grading system for predicting the prognosis of patients with adult soft-tissue sarcomas on the basis of 3 criteria (tumor differentiation, necrosis, and MIB-1 score) and replaces the mitotic count in the French system with MIB-1 immunohistochemical staining. Four surgical pathologists from 4 institutions who had experience in diagnostic soft-tissue tumor pathology reviewed 130 cases of soft-tissue sarcoma and independently determined histologic type and grade. The validity of histologic diagnosis was measured by sensitivity and specificity, and that of grading was measured by kappa statistics and percentage agreement with the diagnosis of the expert panel at the National Cancer Center, which was defined as a gold standard. Interobserver reproducibility was measured by kappa and by percentage agreement between the diagnoses of the 4 pathologists. The validity of the diagnosis of histologic type was high for synovial sarcoma, small round-cell sarcoma, and liposarcoma (sensitivity 89% to 100%; specificity, 98% to 100%) but low for malignant fibrous histiocytoma (MFH) and spindle-cell sarcoma (73% to 75%; 93% to 95%). For the grading, the validity of the MIB-1 grade was substantial (kappa = 0.68; agreement, 79%) and higher than that of the mitosis grade (0.54; 69%). The most valid component was tumor differentiation (kappa = 0.79), followed by tumor necrosis (0.66), MIB-1 score (0.59), and mitotic score (0.37). Interobserver reproducibility of histologic diagnosis was high for small round-cell sarcoma, synovial sarcoma, and liposarcoma (kappa = 0.92, 0.90, 0.87; percentage agreement = 99%, 97%, 96%, respectively); for grading, reproducibility was highest for tumor differentiation (0.78; 87%) and second highest for MIB-1 grade (0.68; 79%). We conclude that diagnosis of the type of soft-tissue sarcoma for synovial sarcoma, small round-cell sarcoma, and liposarcoma and the MIB-1 grading system based on tumor differentiation are highly valid and reproducible among Japanese pathologists who are familiar with the grading system, whereas re-evaluation of histologic criteria is essential for other histologic types such as MFH and spindle-cell sarcoma.

Antigens, Nuclear↗
PubMed2006

Sarcomas often express constitutive nitric oxide synthases (NOS) but infrequently inducible NOS.

Nitric oxide (NO) has a dual action in tumors, with both pro-tumor and anti-tumor activities. NO is produced by nitric oxide synthases (NOS). There are three enzyme isoforms: two of them are constitutively produced (neuronal or brain NOS and endothelial NOS), and one is an inducible form (iNOS). NOS expression has been shown in several epithelial tumors, but there is no report addressing NOS expression in sarcomas. The authors evaluated the expression of NOS in 97 cases of various sarcomas spotted in duplicate in a tissue array paraffin block. Eighty-four of the 97 tumor specimens (86.6%) expressed nNOS, and most of them showed a strong expression of the isoenzyme. Only chondrosarcomas and liposarcomas had significant numbers of negative cases, and all pleomorphic sarcomas, alveolar soft part sarcomas, angiosarcomas, gastrointestinal stromal tumors, and synovial sarcomas showed some degree of positivity. Forty-three cases (44.4%) showed eNOS immunostaining, but only 15.5% showed a strong signal, with emphasis on angiosarcomas, chondrosarcomas, alveolar soft part sarcomas, and synovial sarcoma. Strong expression of iNOS was observed in only 9 cases (9.3%), with weak expression in another 26 cases (26.8%). Strong expression of iNOS was found in malignant peripheral nerve sheet tumors, liposarcomas, pleomorphic sarcomas, fibrosarcomas, chondrosarcomas, and synovial sarcomas. Apparently alveolar soft part sarcomas are unusual in their capacity of expression of NOS isoforms, and in a very peculiar pattern. In conclusion, sarcomas in general commonly express constitutive NOS, and only a few types of sarcomas can express iNOS, the isoenzymes capable of releasing large amounts of NO. More comprehensive studies should be performed to better understand the clinical importance of NOS expression and NO production in sarcomas.

Humans↗
PubMed2005

Disruption of fibroblast growth factor signal pathway inhibits the growth of synovial sarcomas: potential application of signal inhibitors to molecular target therapy.

PURPOSE: Synovial sarcoma is a soft tissue sarcoma, the growth regulatory mechanisms of which are unknown. We investigated the involvement of fibroblast growth factor (FGF) signals in synovial sarcoma and evaluated the therapeutic effect of inhibiting the FGF signal. EXPERIMENTAL DESIGN: The expression of 22 FGF and 4 FGF receptor (FGFR) genes in 18 primary tumors and five cell lines of synovial sarcoma were analyzed by reverse transcription-PCR. Effects of recombinant FGF2, FGF8, and FGF18 for the activation of mitogen-activated protein kinase (MAPK) and the growth of synovial sarcoma cell lines were analyzed. Growth inhibitory effects of FGFR inhibitors on synovial sarcoma cell lines were investigated in vitro and in vivo. RESULTS: Synovial sarcoma cell lines expressed multiple FGF genes especially those expressed in neural tissues, among which FGF8 showed growth stimulatory effects in all synovial sarcoma cell lines. FGF signals in synovial sarcoma induced the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and p38MAPK but not c-Jun NH2-terminal kinase. Disruption of the FGF signaling pathway in synovial sarcoma by specific inhibitors of FGFR caused cell cycle arrest leading to significant growth inhibition both in vitro and in vivo. Growth inhibition by the FGFR inhibitor was associated with a down-regulation of phosphorylated ERK1/2 but not p38MAPK, and an ERK kinase inhibitor also showed growth inhibitory effects for synovial sarcoma, indicating that the growth stimulatory effect of FGF was transmitted through the ERK1/2. CONCLUSIONS: FGF signals have an important role in the growth of synovial sarcoma, and inhibitory molecules will be of potential use for molecular target therapy in synovial sarcoma.

Animals↗
PubMed1998

Second malignancies after treatment for Ewing's sarcoma: a report of the CESS-studies.

PURPOSE: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing's Sarcoma Studies CESS 81 and CESS 86. MATERIALS AND METHODS: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing's sarcoma trials CESS 81 (recruitment period 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete surgery (n = 162), surgery plus postoperative radiotherapy with 36-46Gy (n = 274), or definitive radiotherapy with 46-60Gy (n = 212). The median follow-up at the time of this analysis was 5.1 years, the maximum follow-up 16.5 years. RESULTS: The overall survival of all patients including metastatic patients was 55% after 5 years, 48% after 10 years, and 37% after 15 years. Eight out of 674 patients (1.2%) developed a SM. Five of these were acute myelogenic leukemias (n = 4) or MDS (n = 1), and three were sarcomas. The interval between diagnosis of Ewing's sarcoma and the diagnosis of the SM was 17-78 months for the four AMLs, 96 months for the MDS and 82-136 months for the three sarcomas. The cumulative risk of an SM was 0.7% after 5 years, 2.9% after 10 years, and 4.7% after 15 years. Out of five patients with AML/MDS, three died of rapid AML-progression, and two are living with disease. Local therapy (surgery vs. surgery plus postoperative irradiation vs. definitive radiotherapy) had no impact on the frequency of AML/MDS, but local therapy did influence the risk of secondary sarcomas. All three patients with secondary sarcomas had received radiotherapy; however, all three sarcomas were salvaged by subsequent treatment and are in clinical remission with a follow-up of 1 month, 4.3 years, and 7.5 years after the diagnosis of the secondary sarcoma. Thus far, SM contributed to less than 1 % (3/328) of all deaths in the CESS-studies. CONCLUSIONS: The risk of leukemia after treatment for Ewing's sarcoma is probably in the range of 2%. The risk of solid tumors also seems to be low within the first 10 years after treatment and remains in the range of 5 % after 15 years. In the CESS-studies, less than 1% of all deaths within the first 10 years after diagnosis were caused by SM. Effective salvage therapy for secondary sarcomas is feasible.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Patterns of spread of recurrent intraabdominal sarcoma.

A prominent site for recurrence of retroperitoneal and visceral sarcoma is the abdominal cavity. In an attempt to understand the causation of local and regional recurrence, 21 sarcoma patients who had previously undergone "complete" surgical removal of the primary tumor were prospectively studied. Data were obtained retrospectively from the first operation and prospectively from the reoperative procedure at the Washington Cancer Institute. At the primary and reoperative surgeries, 9 abdominopelvic regions and 21 sites were scored and then cataloged in a standardized fashion. Tumor locations and surgical resections were statistically analyzed in an attempt to establish patterns of recurrence within the abdomen and pelvis. There was a significant difference in sites of recurrence when sarcomas that involved the parietal structures were compared with those that involved small bowel. Peritoneal implants (nodular recurrences) were uniformly present in both groups. In contrast, resection site recurrences were very common with primary sarcomas invested by parietal peritoneum, while they were absent in those covered by visceral peritoneum. When primary surgeries were compared with reoperations, there was an increasing intraabdominal dissemination; the mean number of regions increased from 1.81 to 5.13. The change in distribution of sarcoma deposits at reoperation was greatest in right upper (because of liver surface) central and pelvic abdominopelvic regions and lowest in the left upper and epigastrium. The four anatomic sites that revealed a significant increase in involvement at the time of recurrence were the greater omentum, liver surface, large bowel, and the cul-de-sac of Douglas (all p < 0.002). Regions with tumor involvement or regions subjected to surgical trauma at the time of primary sarcoma resection were significantly more likely to show sarcoma deposits than to be sarcoma free at reoperation. These data taken together may suggest that sarcoma tumor emboli are frequently present in the abdomen at the time of resection of the primary cancer and that these tumor emboli are entrapped in fibrinous material at or immediately adjacent to sites of surgical trauma and along narrow margins of resection. Tumor cell entrapment of sarcoma emboli released into the peritoneal cavity prior to or at the time of sarcoma resection may help explain the distribution of nodular and fusiform recurrence of abdominopelvic sarcoma.

Abdominal Neoplasms↗
PubMed2004

Characterization of sarcomas by means of gene expression.

Sarcomas represent a heterogeneous group of diseases of a variety of recognized histologic types. Among these subtypes is malignant fibrous histiocytoma (MFH), a diagnosis no longer recognized as a specific diagnosis at some institutions. In this study, gene expression in 38 histologically well-defined sarcoma samples, 17 MFH samples, 12 samples of sarcomas classified simply as high-grade sarcoma (NOS, standing for "not otherwise specified"), and 26 other mesenchymal tumors was determined at Gene Logic Inc (Gaithersburg, MD), with the use of Affymetrix GeneChip U_133 arrays containing approximately 40,000 known genes and expressed sequence tags (ESTs). Gene-expression analysis was performed with the use of the Gene Logic Gene Express(R) Software System. Differences in gene expression were quantified as the fold change in gene expression between the various sets of well-defined sarcomas. A set of genes was then identified that could be used to distinguish the well-defined sets of 11 liposarcomas, 9 leiomyosarcomas, 4 synovial sarcomas, 8 schwannomas, and 12 cases of aggressive fibromatosis through the use of Eisen clustering. Eisen clustering was then repeated with the same set of gene fragments with the sample set of 38 histologically well-defined sarcomas, the 17 sarcomas classified as MFH, 12 sarcomas classified as high-grade sarcoma (NOS), and 26 other mesenchymal tumors. Under these conditions, each of the samples of well-defined sarcoma formed distinct clusters that contained some of the MFH and NOS samples. In addition, distinct clusters were observed that contained only MFH and NOS samples. We conclude that gene-expression patterns may be useful in helping further classify subtypes of sarcomas.

Adult↗
PubMed2001

Virologic and immunologic parameters that predict clinical response of AIDS-associated Kaposi's sarcoma to highly active antiretroviral therapy.

The purpose of the work was to assess the predictive value of biologic factors on the efficacy of highly active antiretroviral therapy alone or combined with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS-Kaposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe initial clinical status. Median follow-up was 652 d. The main outcome measures were as follows: best Kaposi's sarcoma clinical response; Kaposi's-sarcoma-associated herpesviral load in peripheral blood mononuclear cells using real-time quantitative polymerase chain reaction (non-detectable if less than 100 copies per microg); human immunodeficiency viral charge in plasma (non-detectable if less than 200 copies per ml); and CD4 lymphocyte count. Time to undetectable Kaposi's-sarcoma-associated herpesviral load, time to undetectable human immunodeficiency viral charge, and time to CD4 >or= 150 per microl were also recorded over time, from 2 mo measurements. Patients were staged according to the AIDS Clinical Trials Group-based tumor, immune, systemic staging system criteria. At baseline, Kaposi's sarcoma was progressive for 25 (96%) of the 26 enrolled patients. Complete or partial response to highly active antiretroviral therapy alone or combined with chemotherapy was achieved in 22 patients (85%). Median time to clinical response was estimated at 251 d. Clinical response was faster in patients without chemotherapy at baseline (p = 0.003) as well as in patients not previously treated with reverse transcriptase inhibitors (p = 0.0012). Using univariable analyses, predictive factors of clinical response were undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.013), undetectable human immunodeficiency viremia (p = 0.03), and relative variation of CD4 lymphocytes (p = 0.004). Using multivariable analysis, undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.009) and relative variation of CD4 (p = 0.005) were independently selected as having a predictive value for clinical response. Occurrence of nondetection of either Kaposi's-sarcoma-associated herpesvirus or human immunodeficiency virus was not associated with baseline CD4 value. Kaposi's-sarcoma-associated herpesvirus quantitative viral charge is an independent predictive factor of the efficacy of highly active antiretroviral therapy on AIDS-Kaposi's sarcoma. Our results support immune reconstitution as a mechanism of response of Kaposi's sarcoma to highly active antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Absence of SYT-SSX fusion products in soft tissue tumors other than synovial sarcoma.

The chromosomal translocation t(X;18), which generates SYT-SSX1 and SYT-SSX2 fusion products, is a sensitive marker for synovial sarcoma; most synovial sarcomas test positive for this marker. However, few studies have addressed the presence of t(X;18) or its fusion products in spindle cell sarcomas in the differential diagnosis of synovial sarcoma. We studied the presence of the SYT-SSX fusion products with reverse transcriptase polymerase chain reaction on frozen tissue samples of 24 synovial sarcomas and 24 other spindle cell sarcomas, including 12 malignant peripheral nerve sheath tumors. In cases histopathologically diagnosed as synovial sarcoma, SYT-SSX fusion products were detected in 21 of 24 (87%) lesions. No evidence of these fusions was found in 12 malignant peripheral nerve sheath tumors, 2 hemangiopericytomas, 3 leiomyosarcomas, 2 fibrosarcomas, 1 poorly differentiated sarcoma (malignant fibrous histiocytoma), 1 sarcoma with rhabdoid features, and 2 sarcomas not otherwise specified. One lesion with histologic, immunohistologic, and ultrastructural features indeterminate for a diagnosis of synovial sarcoma or malignant peripheral nerve sheath tumor was studied and was positive for SYT-SSX1. The SYT-SSX fusion products appear specific for synovial sarcoma and are not seen in other spindle cell lesions in its differential diagnosis.

Adult↗
PubMed1999

Poorly differentiated synovial sarcoma: an analysis of clinical, pathologic, and molecular genetic features.

Poorly differentiated synovial sarcoma is a variant of synovial sarcoma in which the tumor cells lack the bland spindle cell appearance of the usual type monophasic synovial sarcoma. Although poorly differentiated synovial sarcoma has been recognized as an entity for many years, no series addressing the clinicopathologic features of this variant have appeared. We describe the histologic, immunohistologic, and molecular findings of a series of 20 poorly differentiated synovial sarcomas. Three types of poorly differentiated synovial sarcoma can be recognized: a large cell epithelioid variant, a small cell variant, and a high-grade spindle cell variant. Epithelial membrane antigen reactivity was seen in 95% of cases, and reactivity for cytokeratin was seen in 42%. The S100 antigen was expressed in 63% of cases. Electron microscopic findings in poorly differentiated synovial sarcoma parallel those found in usual type synovial sarcoma. In 10 cases, material was available for molecular studies; 9 of 10 cases showed the presence of t(X;18) or the associated fusion gene product. These data indicate that poorly differentiated synovial sarcoma is a lesion that shares immunologic, ultrastructural, and molecular characteristics with the usual synovial sarcoma. Follow-up data were available in 16 patients with a mean follow-up of 39 months. Eight patients died with a mean survival time of 33 months. Poorly differentiated synovial sarcoma is a variant of synovial sarcoma that may be associated with a poor prognosis.

Adolescent↗
PubMed1995

Prognostic factors predictive of survival for truncal and retroperitoneal soft-tissue sarcoma.

OBJECTIVE: The authors identified prognostic factors relevant to clinical outcomes (especially survival) in truncal and retroperitoneal soft-tissue sarcoma. SUMMARY BACKGROUND DATA: These results can be used to optimize surgical management and select patients most likely to benefit from novel therapeutic strategies in future trials. METHODS: A retrospective analysis was performed of a prospectively compiled database of 183 consecutive patients with truncal and retroperitoneal sarcomas seen at the Brigham and Women's Hospital and the Dana Farber Cancer Institute between 1970 to 1994. RESULTS: For truncal sarcoma, multivariate analysis showed that high-grade histology was associated with an eightfold increased risk of death compared with low-grade histology (p = 0.001). In addition to grade, gross positive margin of resection (p = 0.001), microscopic positive margin (p = 0.023), and tumors greater than 5 cm in size (p = 0.018) were important independent prognostic factors for survival. In this series, postoperative radiation therapy for truncal sarcoma was associated with a 2.4-fold decreased risk of death compared with truncal sarcoma patients receiving no adjuvant radiation therapy, having adjusted for the other prognostic factors (p = 0.030). In contrast, for retroperitoneal sarcoma, multivariate analysis showed that high-grade and intermediate-grade histology were associated with a five- to sixfold increased risk of death compared with low-grade histology (p = 0.009). In addition to grade, gross positive margin of resection (p = 0.001) and microscopic positive margin (p = 0.004) were important independent prognostic factors for survival in retroperitoneal sarcoma. Patients who received either preoperative or postoperative chemotherapy for retroperitoneal sarcoma had a 4.6-fold (p = 0.002) and 3-fold (p = 0.010) increased risk of death, respectively, compared with patients receiving no adjuvant chemotherapy, having adjusted for the other prognostic factors. CONCLUSIONS: The histologic grade and the margin of resection are prognostic for survival in both truncal and retroperitoneal soft-tissue sarcoma. Tumor size was an independent prognostic factor for truncal sarcoma, but not for retroperitoneal sarcoma. Postoperative adjuvant radiation was beneficial to overall survival for truncal sarcoma. In this series of patients receiving a heterogeneous mixture of chemotherapeutic regimens-either as preoperative "neoadjuvant" therapy or as postoperative "adjuvant" therapy, there were no beneficial effects on survival compared with nonrandomized patients not receiving chemotherapy.

Adult↗
PubMed1992

Bronchopulmonary Kaposi's sarcoma in patients with AIDS.

BACKGROUND: Kaposi's sarcoma is the most common secondary neoplasm to complicate HIV infection and may cause pulmonary disease. METHODS: A prospective study was carried out in 140 consecutive patients who were HIV seropositive and required bronchoscopy for new respiratory symptoms of at least two weeks' duration, with either a chest radiographic abnormality or abnormality of pulmonary function. The patients were classified into those with single local endobronchial lesions of Kaposi's sarcoma or generalised widespread lesions. Before bronchoscopy all patients had routine simple pulmonary function tests and chest radiography. RESULTS: Thirty nine (21%) patients had evidence of cutaneous Kaposi's sarcoma. Nineteen of the 39 were found to have endobronchial Kaposi's sarcoma lesions at bronchoscopy, but none of those who did not have cutaneous Kaposi's sarcoma. Respiratory symptoms of cough and breathlessness and radiographic abnormalities were attributed to Kaposi's sarcoma in this group, except in four patients who had concomitant pneumocystis pneumonia. Eight patients had local endobronchial Kaposi's sarcoma lesions and 11 had extensive lesions. Patients with extensive lesions had more widespread radiographic abnormalities; four of the patients with local endobronchial lesions had normal chest radiographs. All patients had reduced transfer factor for carbon monoxide and transfer coefficient, whereas patients with extensive endobronchial lesions also had reductions in forced expiratory volume in one second and forced vital capacity. Median survival (with palliative chemotherapy with vincristine and bleomycin) was only seven months. In three patients who needed further diagnostic bronchoscopy endobronchial lesions had regressed while they were having chemotherapy. CONCLUSIONS: This study suggests that endobronchial Kaposi's sarcoma is a relatively common finding in patients with AIDS and is particularly common in patients with cutaneous Kaposi's sarcoma who present with respiratory illness. Endobronchial Kaposi's sarcoma causes respiratory disease and abnormalities of pulmonary function. Pulmonary Kaposi's sarcoma should be considered as a possible cause for respiratory illness in any patient with cutaneous Kaposi's sarcoma.

Acquired Immunodeficiency Syndrome↗