Category Of Sarcoma Research Articles

The Landscape of Alterations from 1407 Ultra-Rare Sarcomas from the AACR GENIE Database: Clinical Implications.

Ultra-rare sarcomas (URS) comprise a group of orphan diseases with an incidence of ≤1/1,000,000 people per year. We aimed to assess clinically actionable genomic alterations in URS. Data were extracted from the GENIE database using cBioPortal. OncoKB was used to assess for clinical actionability of mutations. Tumor mutational burden (TMB) was inferred from clinical sequencing data. Soft tissue (ST) URS made up 23.5% of ST sarcoma cases, and bone URS made up 16.5% of bone sarcoma cases. The most commonly mutated gene in all four groups was TP53. The most common fusions involved EWSR1. The most common copy-number variations included deletions of CDKN2A and CDKN2B and amplifications of MDM2 and CDK4. TMB was generally low across all four categories of sarcoma, though there was considerable heterogeneity, with 3.8% of ST URS and 0.55% of bone URS having high TMB. We find Level 1 alterations (FDA-recognized biomarker predictive of response to an FDA-approved drug) in 10.0% of ST URS compared with 7.1% of ST non-URS, 1.1% of bone URS, and 4.5% of bone non-URS. Level 1-3 alterations (also include alterations for which there are standard-of-care drugs or clinical evidence supporting a drug) were seen in 27.8% of ST URS, 25.2% of ST non-URS, 20.9% of bone URS, and 17.4% of bone non-URS. Clinically actionable genomic alterations are seen in a substantial fraction of URS. Clinical sequencing in advanced URS has the potential to guide the treatment of a significant portion of patients with URS.

Epidemiological Study of Hepatopancreatobiliary Sarcoma in Iran, 2010 - 2014

Background: Hepatopancreatobiliary (HPB) malignancies are a relatively rare but important type of cancer with usually poor prognosis. Prompt diagnosis and treatment are crucial to improving the patient’s outcome. For this issue, acknowledgment of epidemiological characteristics is helpful. Objectives: In this study, the epidemiological characteristics of cases with HPB sarcoma among Iranian patients were assessed. Methods: In this epidemiological study, 133 consecutive cases with HPB sarcoma in Iran from 2010 to 2014 were evaluated, including gallbladder, pancreas, hepatic, pancreatic body and head, and other biliary tumors. Results: Nine gallbladder sarcoma cases were reported between 2010 and 2014, accounting for 6.7% of all HPB sarcoma cases, and leiomyosarcoma was the most common. A total of 16 patients of pancreatic origin were reported during this period, with the highest rate of 6 cases in 2011; in this sarcoma category, malignant type spindle cell tumor was the most common type accounting for 12.5% of all cases. Ninety-five cases of liver sarcomas were reported generally. Non-specified and desmoplastic small round cell tumors were the most common types. Five cases of pancreatic head sarcomas were reported during 2010 - 2013. There was no predominant tumor type. Five cases of pancreatic head sarcoma were reported during 2010 - 2013. There was no dominant tumor type. About the other biliary tract sites, six patients were reported. Gastrointestinal stromal sarcoma was the most common type. Conclusions: Hepatopancreatobiliary sarcoma in the Iranian population generally has diverse types, and there are different patterns according to the age and sex distribution in patients according to the initial location of the tumor and also their pathological subtypes.

Recurrent EWSR1::COLCA2 Fusions Define a Novel Sarcoma With Spindle/Round Cell Morphology and Strong Predilection for the Sinonasal Tract.

The last 2 decades have attended a dynamic evolution in the nosology of poorly differentiated sinonasal tract malignancies, with several new molecularly defined entities having been described in addition to delineation of the genetic driver/s of some established older entities. These discoveries, however, mostly concerned epithelial-derived neoplasms (carcinomas). Adamantinoma-like Ewing sarcoma and biphenotypic sinonasal sarcoma are the major representatives of the newly defined mesenchymal categories. The colorectal cancer associated 2 (COLCA2) has been discovered recently as a colorectal cancer risk gene locus, but fusions involving this gene have not been well characterized. We, herein, describe clinicopathologic and molecular features of a novel sinonasal sarcoma characterized by undifferentiated spindle/round cell morphology and defined by recurrent EWSR1::COLCA2 fusions. All patients (n=5) were adults (3 female and 2 male) with a median age of 46 years (range, 23 to 60y). The tumors originated in different subsites of the sinonasal tract with frequent multisite involvement. Original diagnoses were undifferentiated or unclassified round cell/spindle cell neoplasm/sarcoma (n=4) and neuroendocrine carcinoma (n=1). Surgery with or without adjuvant chemoradiation was the treatment in all cases. At the last follow-up, 1 patient developed multiple local recurrences over 21 years and another developed local recurrence and distant metastasis to bone 27 months after diagnosis. A third patient developed local recurrence 11 months later. Two patients were disease-free at 23, and 24 months. Histology showed nondescript highly cellular neoplasms with an admixture of spindled and round cells disposed into solid sheets and fascicles with brisk mitotic activity. Immunohistochemistry was negative for all lineage-specific markers with only limited focal membranous CD99 (4 of 5 cases) and weak pankeratin (1 of 5 cases) expression. Targeted RNA sequencing revealed an EWSR1::COLCA2 fusion, verified by EWSR1 fluorescence in situ hybridization, in all cases. This series identifies a novel member in the undifferentiated spindle/round cell sarcoma category with strong predilection for the sinonasal tract. None of >10,000 epithelial and mesenchymal neoplasms tested at the authors' centers during the same period showed this fusion, highlighting rarity of tumors carrying this gene fusion. Accordingly, molecular testing of unclassified sinonasal malignancies/sarcomas showing round and spindle cell morphology is recommended to enhance the identification and further characterization of this entity.

Linking Immunity with Genomics in Sarcomas: Is Genomic Complexity an Immunogenic Trigger?

Sarcomas comprise a collection of highly heterogeneous malignancies that can be grossly grouped in the categories of sarcomas with simple or complex genomes. Since the outcome for most sarcoma patients has barely improved in the last decades, there is an urgent need for improved therapies. Immunotherapy, and especially T cell checkpoint blockade, has recently been a game-changer in cancer therapy as it produced significant and durable treatment responses in several cancer types. Currently, only a small fraction of sarcoma patients benefit from immunotherapy, supposedly due to a general lack of somatically mutated antigens (neoantigens) and spontaneous T cell immunity in most cancers. However, genomic events resulting from chromosomal instability are frequent in sarcomas with complex genomes and could drive immunity in those tumors. Improving our understanding of the mechanisms that shape the immune landscape of sarcomas will be crucial to overcoming the current challenges of sarcoma immunotherapy. This review focuses on what is currently known about the tumor microenvironment in sarcomas and how this relates to their genomic features. Moreover, we discuss novel therapeutic strategies that leverage the tumor microenvironment to increase the clinical efficacy of immunotherapy, and which could provide new avenues for the treatment of sarcomas.

Towards applying NMR relaxometry as a diagnostic tool for bone and soft tissue sarcomas: a pilot study

This work explores what Fast Field-Cycling Nuclear Magnetic Resonance (FFC-NMR) relaxometry brings for the study of sarcoma to guide future in vivo analyses of patients. We present the results of an ex vivo pilot study involving 10 cases of biopsy-proven sarcoma and we propose a quantitative method to analyse 1H NMR relaxation dispersion profiles based on a model-free approach describing the main dynamical processes in the tissues and assessing the amplitude of the Quadrupole Relaxation Enhancement effects due to 14N. This approach showed five distinct groups of dispersion profiles indicating five discrete categories of sarcoma, with differences attributable to microstructure and rigidity. Data from tissues surrounding sarcomas indicated very significant variations with the proximity to tumour, which may be attributed to varying water content but also to tissue remodelling processes due to the sarcoma. This pilot study illustrates the potential of FFC relaxometry for the detection and characterisation of sarcoma.

Abstract IA19: Emerging genetic mechanisms in undifferentiated round cell sarcomas

Abstract Undifferentiated round cell sarcomas (URCS) occurring in pediatric and young adults are defined by a primitive morphology reminiscent of Ewing sarcoma, but lack the canonical EWSR1-ETS gene fusion. More than >90% of EWSR1-negative URCS are instead characterized by either a CIC-DUX4 fusion or a genetic abnormality involving BCOR. The latter group includes intra-chromosomal paracentric inversions (BCOR-CCNB3), inter-chromosomal fusions (BCOR-MAML3), or BCOR internal tandem duplications (ITD). Irrespective of their variable mechanism for dysregulation, the tumors share a similar phenotype and a BCOR upregulation at transcriptional and protein levels. In contrast, CIC-DUX4 URCS are characterized by a distinct transcriptional upregulation of PEA3 transcription factors (ETV1/4/5). For practical and treatment purposes, URCS have been regarded as “Ewing sarcoma-like” and have been managed similarly to the Ewing sarcoma family of tumors, despite their poor chemotherapy responses and aggressive clinical behavior. Alternatively these tumors are grouped by default in an “undifferentiated sarcoma category,” with their clinical management being often biased. Despite the wide spectrum of genetic abnormalities, the unifying concept is that the various gene partners or ITDs disrupt the C-terminal repressor domains of both CIC and BCOR, resulting in an oncogenic transcriptional activation of target genes. In URCS with BCOR ITD, the ITD sequences located at the C-terminal may affect the PUFD domain conformation of the BCOR protein, which might interfere with PCGF1 binding and thus could affect the PRC1-related epigenetic modifications. Citation Format: Cristina Antonescu. Emerging genetic mechanisms in undifferentiated round cell sarcomas [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA19.

Chondrosarcoma evolution of sacral joint - iliac in a dog: Case report

Chondrosarcoma is a malignant neoplasm of bone that develops from the cartilaginous tissues, classified in the category of sarcomas, among the three tumors that most affect the pelvic region of dogs. The objective of this report was to describe the case of a chondrosarcoma located in the right sacroiliac joint in an 8-year-old female canine patient of the German shepherd breed. In this way, we emphasize the importance of the radiographic examination in the diagnostic conclusion, emphasizing that the histopathological examination is the examination of predilection for the definitive diagnosis of this affection.

BCOR–CCNB3 fusions are frequent in undifferentiated sarcomas of male children

The BCOR–CCNB3 fusion gene, resulting from a chromosome X paracentric inversion, was recently described in translocation-negative ‘Ewing-like’ sarcomas arising in bone and soft tissue. Genetic subclassification of undifferentiated unclassified sarcomas may potentially offer markers for reproducible diagnosis and substrates for therapy. Using whole transcriptome paired-end RNA sequencing (RNA-seq) we unexpectedly identified BCOR–CCNB3 fusion transcripts in an undifferentiated spindle-cell sarcoma. RNA-seq results were confirmed through direct RT-PCR of tumor RNA and cloning of the genomic breakpoints from tumor DNA. Five additional undifferentiated sarcomas with BCOR–CCNB3 fusions were identified in a series of 42 pediatric and adult unclassified sarcomas. Genomic breakpoint analysis demonstrated unique breakpoint locations in each case at the DNA level even though the resulting fusion mRNA was identical in all cases. All patients with BCOR–CCNB3 sarcoma were males diagnosed in mid childhood (7–13 years of age). Tumors were equally distributed between axial and extra-axial locations. Five of the six tumors were soft-tissue lesions with either predominant spindle-cell morphology or spindle-cell areas interspersed with ovoid to round cells. CCNB3 immunohistochemistry showed strong nuclear positivity in five tumors before oncologic therapy, but was patchy to negative in post-treatment tumor samples. An RT-PCR assay developed to detect the fusion transcript in archival formalin-fixed tissue was positive in all six cases, with high sensitivity and specificity in both pre- and post-treated samples. This study adds to recent reports on the clinicopathologic spectrum of BCOR–CCNB3 fusion-positive sarcomas, a newly emerging entity within the undifferentiated unclassified sarcoma category and describes a simple RT-PCR assay that in conjunction with CCNB3 immunohistochemistry can be useful in diagnosing these tumors.

Why do patients with radiation-induced sarcomas have a poor sarcoma-related survival?

Background:This study aims to provide reasons for the poor sarcoma-related survival in patients with radiation-induced sarcoma (RIS).Methods:We performed a case–control study comparing sarcoma-related survival of 98 patients with RIS to that of 239 sporadic high-grade malignant sarcomas.Results:The cumulative sarcoma-related 5-year survival was 32% (95% confidence interval (CI): 22–42) for patients with RIS vs 51% (95% CI: 44–58) for controls (P<0.001). Female gender, central tumour site and incomplete surgical remission were significantly more frequent among RIS patients than in controls. In multivariate analysis incomplete surgical remission (hazard ratio (HR) 4.48, 95% CI: 3.08–6.52), metastases at presentation (HR 2.93, 95% CI: 1.95–4.41), microscopic tumour necrosis (HR 1.88, 95% CI: 1.27–2.78) and central tumour site (HR 1.71, 95% CI: 1.18–2.47) remained significant adverse prognostic factors, but not sarcoma category (RIS vs sporadic).Conclusion:The poor prognosis of RIS patients are not due to the previous radiotherapy per se, but related to the unfavourable factors – central tumour site, incomplete surgical remission, microscopic tumour necrosis and the presence of metastases, the two former factors overrepresented in RIS.

Phase II evaluation of intravenous vinorelbine (Navelbine) in recurrent or refractory pediatric malignancies: A Children's Oncology Group study

A Phase II trial was developed to determine the efficacy and toxicity of intravenous vinorelbine, a semi-synthetic vinca alkaloid, in children, adolescent, and young adults with recurrent or refractory solid malignancies. Fifty patients were enrolled among three strata: soft tissue sarcomas [rhabdomyosarcoma (RMS), non-rhabdomyosarcoma, primitive neuroepithelial tumor] (20 patients); brain tumors [astrocytoma (4 patients), medulloblastoma (2 patients), other (16 patients)] (22 patients); neuroblastoma (8 patients). Vinorelbine was given weekly for 6 consecutive weeks during an 8-week interval. The response rate and toxicity profile was assessed. Among the first 35 patients treated at 33.75 mg/m(2)/dose, 25 experienced grades 3-4 neutropenia (75%). The dose was decreased to 30 mg/m(2)/dose in the remaining 15 patients. The median age was 10 years (range, 1-25). Four responses (one complete, three partial) occurred within the soft tissue sarcoma strata (all with RMS) and two occurred in the brain tumor group (medulloblastoma and astrocytoma). The most common toxicities were hematological and neurological. Vinorelbine at dose of 30 mg/m(2) can be safely administered to children with recurrent or refractory solid malignancies. The study design identified vinorelbine to be active in the sarcoma category, with a response rate of 36% (4/11) among RMS patients.

Roles of immunohistochemistry and detection of SYT-SSX fusion gene in diagnosis of synovial sarcoma

To assess the diagnostic values of immunohistochemistry and SYT-SSX fusion gene detection for synovial sarcoma. Based on clinical features, histological and immunohistochemical profiles, 195 cases of tumors were divided into three diagnostic categories: definitive synovial sarcoma, probable synovial sarcoma and possible synovial sarcoma. RT-PCR Detection of the SYT-SSX fusion gene was performed using paraffin embedded tissue samples. Comparison between RT-PCR and immunohistochemistry results was carried out and their diagnostic value was evaluated. There were 62 (31.8%) definite synovial sarcomas, 49 (25.1%) probable synovial sarcomas and 84 cases (43.1%) possible synovial sarcomas. SYT-SSX fusion gene was detected in 140 (78.2%) cases overall, including 94.7% (54/57) definite synovial sarcomas, 86.0% (37/43) probable synovial sarcomas and 62.0% (49/79) possible synovial sarcomas. In tumors in the certain and probable synovial sarcoma categories, the positive rates of epithelial membrane antigen (EMA) were significantly higher in the SYT-SSX positive cases than SYT-SSX-negative cases (P = 0.022, P = 0.010, respectively). EMA was positively correlated with the presence of SYT-SSX (r(s) = 0.431, P = 0.001, r(s) = 0.463, P = 0.002, respectively). However, such a correlation was not seen in cytokeratin (CK), vimentin or S-100 protein immunostains (P > 0.05). In tumors of possible synovial sarcoma category, there were no significant differences of CK, EMA, vimentin or S-100 protein between SYT-SSX-positive and SYT-SSX-negative tumors. SYT-SSX fusion gene detection is not needed when the conventional approaches are diagnostic. EMA positivity has a similar diagnostic value to that of SYT-SSX by RT-PCR for tumors in the probable synovial sarcoma category. However, detection of SYT-SSX is very important for diagnosis of the tumors in the category of possible synovial sarcoma.

Uterine malignant mixed mullerian tumors should not be included in studies of endometrial carcinoma

Objective Uterine mixed malignant mullerian tumors (MMMT) have traditionally been excluded from clinical trials of endometrial cancer because of a belief that they are more correctly included in the sarcoma category. Recently, investigators have suggested that uterine MMMTs are actually dedifferentiated epithelial tumors and should be treated as such. The current study was undertaken to compare outcomes, stage for stage, of uterine MMMT with poor prognosis endometrial adenocarcinomas. Methods Cases of MMMT from 1996 to 2004 were identified from the Tumor Registry after IRB consent was obtained. Retrospective chart review was performed. Cases were matched by age, stage, performance status, and surgical procedure to controls consisting of grade 3 endometrioid, papillary serous, and clear cell endometrial carcinomas from the same time period. Overall survival was compared using the Log-Rank test. Results 68 patients with MMMT were identified. 23 were excluded due to incomplete records. Patients with MMMT ranged in age from 51 to 95 years (mean 75.3 years). Approximately half of the patients (53%) had stage III or IV disease. Of the controls, 31 (69%) had grade 3 endometrioid, 11 (24%) papillary serous, and 3 (7%) clear cell carcinoma. Median overall survival for all patients with MMMT was significantly shorter than for controls, 18 months (range 0.5–72) versus 36 months (range 0.5–123) ( P = 0.02). Patients with early stage disease (stage I or II) had shorter median survival than controls, 26 months (range 3–7) vs. 95 months (range 4–123) ( P = 0.003). There was no difference in median survival when comparing advanced disease (stage III or IV) to matched controls, 15 months (range 0.5–70) vs. 19 months (range 0.5–100) ( P = NS). Conclusions Patients with uterine MMMT have a poorer prognosis than those patients with high grade epithelial tumors, especially for those with early stage disease. Given the discrepancy in survival, these patients should not be included in studies of endometrial carcinoma. Further investigations are necessary to identify factors to improve survival of these patients.

Mammary NOS-Type Sarcoma With CD10 Expression

We present an extensive immunohistochemical analysis of 7 mammary sarcomas that did not fit into any specific soft tissue sarcoma category. Histologically, they were composed of spindle cells with highly pleomorphic nuclei and abundant mitoses. Our immunohistochemical antibody panel included pan-cytokeratin (CK), basal cell type CKs (34betaE12, CK5/6, CK14, CK17) and vimentin antibodies, antibodies to established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM-myosin), and novel (CD29, 14-3-3sigma) myoepithelial markers, as well as antibodies to CD34, desmin, h-caldesmon, steroid receptors (estrogen, progesterone, androgen), and EGFR (Her-1). Whereas CKs, CD34, desmin, and h-caldesmon were not expressed, all tumors were positive for CD10 and vimentin. CD29 and SMA were observed in 3 cases each (43%), and p63 and calponin in 2 cases each (29%). Other myoepithelial markers and steroid receptors were absent, except androgen receptors, which were expressed in one sarcoma. Five sarcomas showed positivity for EGFR. The distinction of specific, histogenetically defined sarcoma entities (such as leiomyosarcoma, angiosarcoma, liposarcoma) from NOS-type sarcoma with CD10 expression is usually clear-cut because the former exhibit a characteristic histomorphology and immunoprofile. Phyllodes tumors with stromal overgrowth or recurrent phyllodes tumors lacking epithelial structures as well as periductal stromal sarcomas can be ruled out by their frequent expression of CD34 and negativity for myoepithelial markers. The most important differential diagnosis is sarcomatoid metaplastic carcinoma because its treatment includes axillary lymphadenectomy. Since some NOS-type sarcomas with CD10 expression and most metaplastic carcinomas show positivity for CD29, SMA, and p63, differential diagnosis can be extremely difficult and requires extensive immunohistochemical evaluation for CKs and additional myoepithelial markers such as S-100, 14-3-3sigma, and maspin. The immunophenotype of NOS-type sarcomas with CD10 expression suggests that these neoplasms represent a mammary sarcoma variant with myoepithelial features.

The diagnosis and prognosis of synovial tumors in dogs: 35 cases.

Although synovial cell sarcoma is reported to be the most common neoplasm of the canine synovium, this retrospective study of 35 canine synovial tumors found that the majority were of histiocytic origin. Five (14.3%) synovial cell sarcomas were identified by positive immunohistochemical staining with antibodies to cytokeratin. Eighteen (51.4%) histiocytic sarcomas were identified by cell morphology and immunohistochemical staining with antibodies to CD18. Six (17.1%) synovial myxomas were identified by histologic pattern. The remaining six (17.1%) synovial tumors represented a variety of sarcomas, including two malignant fibrous histiocytomas (actin positive), one fibrosarcoma, one chondrosarcoma, and two undifferentiated sarcomas. Rottweilers were overrepresented in the histiocytic sarcoma category and Doberman Pinschers were overrepresented in the synovial myxoma category. The average survival time was 31.8 months for dogs with synovial cell sarcoma, 5.3 months for dogs with histiocytic sarcoma, 30.7 months for dogs with synovial myxoma, and 3.5 months for dogs with other sarcomas. Among the dogs with follow-up information available, metastatic disease was detected in 25% of dogs with synovial cell sarcoma, in 91% of dogs with histiocytic sarcoma, in none of the dogs with synovial myxoma, and in 100% of dogs with other sarcomas. Immunohistochemical staining for cytokeratin, CD18, and smooth muscle actin is recommended to make the diagnosis and thereby predict the behavior of synovial tumors in dogs.

Distinct mdm2/p53 expression patterns in liposarcoma subgroups: implications for different pathogenetic mechanisms.

Recent findings have indicated that TP53 inactivation in sarcomas may result from mutation and/or deletion of the TP53 gene or, alternatively, from binding to the MDM2 gene products. To investigate further a possible role of the two genes in sarcomas, 24 large and deep-seated lipomas and 74 liposarcomas of various subtypes were analysed for mdm2 and p53 overexpression by immunocytochemistry. Nineteen cases of the same series were also molecularly analysed for both MDM2 gene amplification and TP53 mutations, and a further ten cases for non-random chromosomal abnormalities. In the retroperitoneal well-differentiated-dedifferentiated (WD-DD) group, 15/16 WD and 8/8 DD liposarcomas displayed the mdm2+/p53+ phenotype, consistent with MDM2 gene amplification in the absence of TP53 mutations. In the non-retroperitoneal WD-DD group, 5/11 WD liposarcomas also retained the mdm2+/p53+ phenotype whereas all DD liposarcomas showed an immunophenotype and, when assessed, a genotype consistent with mutant TP53. Null mdm2 immunophenotype, coupled with evidence of a specific chromosome translocation t(12;16), was constantly observed in both the usual and the cellular subtypes of myxoid liposarcoma, three cases of which also showed TP53 alterations at the genetic or protein level. Neither mdm2 nor p53 overexpression was observed in the lipomas. The results show the existence of three main pathogenetically distinct groups of liposarcoma. The first retroperitoneal WD-DD group, which represents a novel class of tumours within a single histological category of sarcoma, where MDM2-mediated inactivation of p53 could be related to the pathogenetic mechanism. The second is the non-retroperitoneal WD-DD group, where the TP53 mutations appear to correlate with the dedifferentiation process. The third is the myxoid group, which is characterized by its own unique cytogenetic profile and never shows any involvement of TP53 or MDM2 genes. As for diagnostic significance, the absence of mdm2 and p53 reactivity in lipomas seems to represent a useful marker for differential diagnosis from lipoma-like WD liposarcomas.

KP-1: not a specific marker. Staining of 137 sarcomas, 48 lymphomas, 28 carcinomas, 7 malignant melanomas and 8 cystosarcoma phyllodes

This study documents the reactions of the monoclonal antibody KP-1, which detects histiocytes in paraffin sections, with 137 sarcomas, 48 lymphomas, 28 carcinomas, 7 malignant melanomas and 8 cystosarcoma phyllodes. The soft tissue sarcomas had been previously immunophenotyped. Positive staining was obtained in all categories of sarcoma except clear-cell sarcomas. Most categories of sarcoma showed staining in less than 10% of tumour cells although a minority of leiomyosarcomas showed more extensive staining. Five of 7 malignant melanomas were also positive while all lymphomas and carcinomas were negative. We conclude that KP-1 positivity is not helpful in supporting the histiocytic origin of a tumour and is of limited value in the differential diagnosis of soft tissue sarcomas or their separation from other categories of malignancy.

Mac387: its non‐specificity as a tumour marker or marker of histiocytes

A commercially available monoclonal antibody which detects histiocytes in paraffin sections, Mac387, was reacted with 148 soft tissue sarcomas, 29 carcinomas and 10 malignant melanomas. The soft tissue sarcomas had been previously immunophenotyped. All categories of sarcomas, with the exception of angiosarcomas, were positive. Most showed staining in less than 50% of the tumour cells. Six of 10 adenocarcinomas and three of nine basal cell carcinomas were positive, while squamous carcinomas and malignant melanomas were negative. Normal squamous mucosa and epidermis were also positive. The results of this study suggest that Mac387 is of little value in the differential diagnosis of soft tissue tumours, nor is it a specific histiocytic marker.

Anti—α1-Antichymotrypsin Staining of 194 Sarcomas, 38 Carcinomas, and 17 Malignant Melanomas Its Lack of Specificity as a Tumour Marker

A polyclonal commercially available antiserum to alpha 1-antichymotrypsin (alpha 1ACT) was reacted with 194 sarcomas, 38 carcinomas, and 17 malignant melanomas; 61 of 194 sarcomas, 14 of 38 carcinomas, and 10 of 17 malignant melanomas reacted positively. Thirteen categories of sarcomas were examined. All but one group (haemangiopericytomas) showed positively staining tumour cells. Malignant fibrous histiocytomas, angiosarcomas, and Kaposi's sarcomas showed positive staining in over 70% of tumours. All categories of carcinomas examined, with the exception of transitional cell carcinomas, stained positively. The results of this study suggest that the use of alpha 1ACT antiserum is of little value in the differential diagnosis of either sarcomas or carcinomas, nor can it be used as a specific histiocytic marker.

Cytoplasmic estrogen and progesterone receptor content of uterine sarcomas

Analyses of cytoplasmic estrogen receptor and progesterone receptor were performed on tumor specimens from 32 patients with uterine sarcomas. While the median and maximal quantitative levels of binding were lower than those observed in endometrial carcinomas, examples of estrogen receptor- and progesterone receptor-positive as well as estrogen receptor- and progesterone receptor-negative tumors were observed in all histologic categories of sarcomas. The presence of significant levels of estrogen receptor binding correlated (p less than 0.05) with the presence of progesterone receptor. The receptor binding status did not correlate with the histologic type of sarcoma, clinical stage, primary or metastatic tumor, presence of extrauterine metastases, age, previous exogenous estrogen therapy, mitotic count, or overall differentiation or nuclear differentiation of the sarcoma. The overall and nuclear differentiation of the carcinomatous elements of homologous mixed müllerian tumors did not correlate with receptor status. The presence of significant levels of estrogen receptor did demonstrate a trend (p less than 0.10) favoring enhanced survival through short-term follow-up, but this trend was not demonstrated with survival beyond 36 months. Steroid receptor status did not otherwise affect prognosis or disease-free survival. No correlation between receptor content and response to hormonal therapy or chemotherapy was observed.

Incidence of bone sarcoma in SW England, 1946-74, in relation to age, sex, tumour site and histology

A study is presented of all cases of primary sarcoma of bone registered during the period 1946 to 1974 for a specified population resident in south-western England. Ninety-six per cent of the 365 cases were histologically and radiologically verified and are separated into 8 categories of sarcoma. The number of tumours presenting during each hemi-decade did not markedly diverge from the 5-year mean for the period, nor was any significant change found in tumour incidence during the last 20 years of the survey. The age, sex and site distributions correspond with those reported elsewhere. Age-specific incidence rates are compared with those published for Sweden. For osteosarcoma and Ewing's tumour, both commoner in young people, the two series agree closely up to age 55 years, after which the Swedish incidence rates rise and are not exceeded when, for the present cases, Paget's osteosarcomas are included. Whilst Paget's disease may change the age incidence of some types of bone sarcoma, it is uncertain whether it increases the total number which occur. Differences in tumour incidence between males and females, whether for a specific type or for all bone sarcomas, are seldom statistically significant, but the patterns appear to be consistent.