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PubMed1985

Phase II study of cisplatin in advanced osteogenic sarcoma. European Organization for Research on Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

The activity of cisplatin (CDDP) against advanced osteogenic sarcoma was evaluated in 37 of 50 patients registered by the members of the European Organization for Research on Treatment of Cancer Soft Tissue and Bone Sarcoma Group between 1979 and 1982. All patients had measurable lung metastases. Thirty-one patients (84%) had received previous chemotherapy consisting mainly of high-dose methotrexate, doxorubicin, and vincristine. CDDP (100 mg/m2) was given as a 24-hour continuous infusion every 3 weeks for a minimum of two cycles, with appropriate fluids and diuretics. In the absence of impairment of the renal function and/or myelosuppression, the dose could be escalated by 20%. The overall response rate was 19% (seven responses among 37 patients), with one complete remission for 51 weeks and six partial remissions from 12 to 26 weeks. The median number of courses of CDDP administered was three, ranging from two to 11. Of 143 courses administered, only 18 (12%) had to be modified because of toxicity. In 16% of the patients some transient impairment of the renal function was observed. CDDP adds to the limited number of chemotherapeutic agents with useful properties in osteogenic sarcoma, and CDDP-containing combination chemotherapy regimens should be actively investigated.

Adolescent↗
PubMed1984

[Uterine sarcoma. Retrospective analysis of a series of 22 cases].

37 uterine tumors originally diagnosed as uterine sarcomas at Fondation Bergonié between 1970 and 1982 were histologically reclassified. 15 patients were excluded from this study because of inadequate data or not confirmed initial diagnosis. The 22 remaining cases were classified as leiomyosarcomas 13, endometrial stromal sarcomas 7 and mixed mesodermal sarcomas 2. The mean age of the patients was 56. The cases were classified according to the FIGO staging system. 5 patients had previously undergone (between 1 and 8 years) a subtotal hysterectomy for uterine leiomyoma. 5 patients had stage 1 sarcoma, 13 patients stage III and 2 patients stage IV. 13 patients are dead, 7 are alive without evidence of disease, 2 are alive with evidence of disease. The 5 year actuarial survival rate was 30%. Tumor extent at diagnosis was not correlated with survival. Analysis of failures revealed : 4 metastatic, 5 metastatic and pelvic and 6 isolated pelvic failures. Prognosis was not significantly different between leiomyosarcomas and endometrial stromal sarcomas. There was no pelvic failure in patients with stage I sarcoma (treated by surgery plus radiotherapy). Survival was not found to be correlated with histopathological grade as described in soft tissue sarcomas. Nevertheless a correlation (non significant) was found between survival and mitosis count. Chemotherapy (Cyvadic) was administered in 8 advanced tumors with partial response (always below 50% of the initial tumor) in 5 patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1981

Kaposi's sarcoma: immunohistologic evidence for an endothelial origin.

Factor VIII-related antigen (VIIIR-Ag), a marker for endothelial cells, was used to explore the histogenesis of Kaposi's sarcoma. Formaldehyde-fixed, paraffin-embedded routine histologic sections from 37 cases of Kaposi's sarcoma and from 16 other spindle-cell tumors of the skin were stained for the presence of VIIIR-Ag, using an immunoperoxidase technique. Positive reactions were noted in all cases of Kaposi's sarcoma regardless of their histologic variations. Although the intensity of reaction was greater in cells that lined vascular channels and blood-filled clefts, many intertwining spindle cells contained VIIIR-Ag in their cytoplasm as well. Since VIIIR-Ag is elaborated only by endothelial cells and megakaryocytes, positive immunologic reaction for this factor in the cells of Kaposi's sarcoma strongly supports an endothelial derivation.

Antigens↗
PubMed1982

Transformation-specific cell killing by a cancer-associated galactosyltransferase acceptor and cellular binding.

Cancer-associated galactosyltransferase acceptor (CAGA glycoprotein), a small glycoprotein purified from human malignant effusion that selectively kills transformed cells, was tritiated by reductive methylation in the presence of NaB(3)H(4). CAGA-glycoprotein-sensitive cells (baby-hamster kidney cells transformed by polyoma virus and chick-embryo fibroblasts infected with Ts68 temperature-sensitive mutant of Rous sarcoma virus grown at 37 degrees C, the permissive temperature) bound 3-5-fold more (3)H-labelled CAGA glycoprotein than did their CAGA-glycoprotein-resistant non-transformed counterparts. The Rous-sarcoma-virus-infected chick-embryo fibroblasts grown at non-permissive temperature (41 degrees C) bound an intermediate amount of (3)H-labelled CAGA glycoprotein; however, this intermediate amount appeared to be sufficient to induce inhibition of cell growth when the infected chick-embryo fibroblasts treated at 41 degrees C were switched to 37 degrees C. Binding of (3)H-labelled CAGA glycoprotein was time- and temperature-dependent and was not inhibited by monosaccharide. Binding was completely inhibited by the oligosaccharide liberated by endoglucosaminidase H treatment or by exhaustive Pronase digestion of intact CAGA glycoprotein. However, the isolated oligosaccharide failed to demonstrate the growth-inhibition characteristics of the intact glycopeptide. Binding of (3)H-labelled CAGA glycoprotein was unaffected by co-incubation with the peptide core released by endoglucosaminidase H treatment. (3)H-labelled CAGA glycoprotein bound to intact cells could be removed by trypsin treatment up to 4h after addition of the glycoprotein but not thereafter. This time course paralleled the decreasing reversibility of growth inhibition. However, all (3)H-labelled CAGA glycoprotein was found in the supernatant when cells were first disrupted by sonication followed by trypsin treatment for up to 12h. (3)H-labelled CAGA glycoprotein linked to Sepharose 4B failed to cause growth inhibition in CAGA-glycoprotein-sensitive cells. These findings suggest that binding of CAGA glycoprotein occurs via its oligosaccharide moiety. Binding appears to be a necessary but not sufficient condition to induce cell killing. Growth inhibition appears to depend on internalization of the glycoprotein and the presence of a transformation-specific cell process.

Amino Acids↗
PubMed1995

Carcinosarcomas of the female genital tract. A pathologic study of 29 metastatic tumors: further evidence for the dominant role of the epithelial component and the conversion theory of histogenesis.

Carcinosarcomas of the female genital tract have generally been regarded as a type of sarcoma. Recent evidence suggests, however, that they may be more closely related to carcinoma. The histologic features of 29 carcinosarcomas with documented metastases were analyzed to study the relative importance of the carcinomatous and sarcomatous components and attempt to provide further evidence on the histogenesis of these neoplasms. Patients' ages ranged from 33 to 81 years (mean, 68). The primary tumor originated in the uterus in 17 cases, the ovary in 11, and the fallopian tube in one. Heterologous sarcoma was present in 21 of the primary tumors (72%). Myometrial invasion was present in all 15 of the uterine tumors treated with hysterectomy and consisted only of the carcinomatous component in 12 cases (80%). In two cases, which possibly developed as "collision"-type carcinosarcomas, the myometrium was separately invaded by carcinoma and sarcoma. Myoinvasive tumor consisted solely of sarcoma in one case. Lymphatic-vascular invasion was found in 10 of the primary tumors (eight uterine, two extrauterine) and consisted of pure carcinoma in all instances. The cellular composition of 62 metastases was evaluated. Of these, 51 metastases were diagnosed concurrently with the primary tumor in 21 patients (73%). Eleven metastases were diagnosed from 2 to 26 months after initial treatment. Carcinoma only was found in 43 metastases (70%), both carcinoma and sarcoma in 15 (24%), and sarcoma alone in four (6%). A total of 35 lymph node metastases occurred in 10 cases, consisting of carcinoma alone at 34 sites. The sole example of a purely sarcomatous lymph node metastasis occurred in one of the possible uterine "collision"-type tumors. Intraperitoneal metastases to serosal surfaces or the omentum occurred in 19 cases and consisted of both carcinoma and sarcoma in 14 and carcinoma only in five. Vaginal metastases occurred in four cases and consisted of only carcinoma in two, carcinoma and sarcoma in one and only sarcoma in one. Four patients had distant organ metastases, including one each to the liver (carcinoma only), breast (carcinoma only), bone marrow (sarcoma only), and brain (sarcoma only). Of the 51 concurrent metastases, only carcinoma was present in 37 (73%), both carcinoma and sarcoma in 13 (26%), and sarcoma alone in one. Of the 11 subsequent metastases, carcinoma alone was found in six (55%), sarcoma alone in three (27%), and both carcinoma and sarcoma in two (18%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1986

[Selective shedding of gangliosides by cells of mouse ascitic sarcoma-37].

The profile and content of gangliosides associated with tumour cells of mouse sarcoma-37 and exfoliated from the cell surface were determined. It was shown that 20% of tumour gangliosides shed from the cell surface and only about 7% of all the shed gangliosides were contained in plasma membrane fragments. When incubated in vitro at 37 degrees C for 1 hour, the tumour cells were found to release less than 2% of cellular gangliosides. The main components of cellular gangliosides corresponded in their chromatographic behaviour to GM2 (31-32% of the total ganglioside content), GD3 (17-18%), GD1a (9-11%), GD2 (16-17%) and hematosides (19-21%). The profiles of in vivo and in vitro shed gangliosides were similar but strongly differed from those of cellular gangliosides: the relative content of GM2 was 70-75% and the other gangliosides were found in negligible amounts. The data show that GM2 accumulation in extracellular spaces is rather the result of its selective shedding than the shedding of products of "incomplete" cellular ganglioside synthesis.

Animals↗
PubMed1992

Flow cytometric analysis of uterine sarcoma: ploidy and S-phase rate as prognostic indicators.

Flow cytometry of various gynecological tumors has shown that aneuploid tumors and a high S-phase rate carry a prognosis worse than that of diploid tumors or tumors with a low S-phase. The aim of this study is to investigate the prognostic importance of DNA ploidy and S-phase rate in relation to mitotic count, tumor stage, tumor grade, and histology in 37 patients with uterine sarcoma stages I-IV (FIGO). Flow cytometry was performed on archival paraffin-embedded tumor tissue and the histologic specimens were reviewed by a single pathologist. Nineteen (51%) of the tumors were classified as DNA aneuploid. The S-phase fraction (SPF) was determined in 33 cases. The mean SPF (+/- SD) was 15.0% (+/- 9.5%). The mean SPF was three times higher in aneuploid tumors than in diploid cases. Both the proportion of aneuploid tumors and the mean SPF were significantly higher in later stage tumors, more poorly differentiated tumors, and tumors with a higher mitotic index. No significant differences were seen between histologic types with respect to the two cytometric variables. The 5-year cancer survival rate was only 11% in aneuploid cases compared with 59% in diploid cases (log rank, P = 0.0002). There was a significantly worse prognosis in cases with a higher SPF (P = 0.0009) and in case with a higher mitotic index (P = 0.0016). In the multivariate survival analysis using the Cox proportional hazards model, DNA ploidy showed a significant prognostic value (P = 0.046) even when adjusted for stage, grade, and mitotic index. When adjusted for stage and grade only, SPF showed significant additional prognostic value.

Adult↗
PubMed2001

Survival of children with soft-tissue sarcoma in Europe since 1978: results from the EUROCARE study.

Soft-tissue sarcomas account for 5--8% of all childhood cancers in European countries. In the EUROCARE childhood cancer study, there were 2163 registrations from 17 countries for soft-tissue sarcomas in patients aged 0--14 years during 1978--1989. Of this total, three-quarters were contributed by childhood cancer registries in Germany and the UK. Age-standardised 5-year survival rates of children diagnosed during 1985--1989 were 65% (95% confidence interval (CI) 56--72) for rhabdomyosarcoma, 68% (95% CI 58--77) for fibrosarcoma, 78% (95% CI: 64--87) for other specified soft-tissue sarcomas except Kaposi's and 51% (95% CI 37--65) for 'unspecified' soft-tissue sarcomas. Survival rates increased steadily throughout the 12-year study period for all soft-tissue sarcomas combined, but the increase took place predominantly in the early 1980s for rhabdomyosarcoma. Improvements in survival which had previously been reported from individual countries and in clinical series are confirmed as having taken place throughout much of Europe on a population basis. In a supplementary analysis, there was little indication of a further improvement during 1990--1992.

Adolescent↗
PubMed2006

High WT1 expression is associated with very poor survival of patients with osteogenic sarcoma metastasis.

PURPOSE: Although metastasis is the primary determinant of poor survival of patients with osteogenic sarcoma, some patients live much longer than others, indicating metastatic heterogeneity underlying survival outcome. The purpose of the investigation was to identify genes underlying survival outcome of patients with osteogenic sarcoma metastasis. EXPERIMENTAL DESIGN: We have used microarray to first compare mRNA expression between normal bone and osteogenic sarcoma specimens, identified genes overexpressed in osteogenic sarcoma, and compared expression of the selected gene between a poorly metastatic (SAOS) and two highly metastatic cell lines (LM8 and 143B). Finally, expression of the selected gene was assessed by immunostaining of osteogenic sarcoma samples with known survival outcome. RESULTS: Microarray analysis revealed 5.3-fold more expression of WT1 mRNA in osteogenic sarcoma compared with normal bone and >2-fold overexpression in 143B and LM8 cells compared with SAOS. Furthermore, WT1 mRNA was absent in normal bone (10 of 10) by reverse transcription-PCR but present in osteogenic sarcoma-derived cell lines (5 of 8). One hundred percent (42 of 42) of low-grade osteogenic sarcoma specimens expressed no WT1 as determined by immunostaining; however, 24% (12 of 49) of the high-grade specimens showed intense staining. Mean survival of patients with high-grade metastatic osteogenic sarcoma but low WT1 staining (27 of 37) was 96.5 +/- 129.3 months, whereas mean survival of patients with high-grade metastatic osteogenic sarcoma having intense staining (10 of 37) was 18.3 +/- 12.3 months (P > 0.0143). All splice variants of WT1 mRNA, including a hitherto unknown variant (lacking exons 4 and 5), were found to be expressed in osteogenic sarcoma. CONCLUSION: WT1 seems to be associated with very poor survival of patients with osteogenic sarcoma metastasis.

Base Sequence↗
PubMed1986

Kaposi's sarcoma and HTLV-III: a study in Nigerian adult males.

Sera from 37 adult Nigerian men with Kaposi's sarcoma (KS), 30 contemporaneous controls bearing primary cell carcinoma of the liver (PCL), and 150 healthy non-tumour-bearing negative controls were tested for antibody to human T-cell lymphotropic virus type III/lymphadenopathy associated virus (HTLV-III/LAV) by enzyme-linked immunosorbent assays (ELISA). Certain immunocellular functions were also measured: the chemotactic locomotion of peripheral blood monocytes towards casein, delayed-type cutaneous hypersensitivity reaction to tuberculoprotein and opportunistic infection with the fungus Candida albicans. Sera from all these groups were also tested for markers of previous infections with the viruses cytomegalovirus (CMV), Epstein-Barr virus (EBV), hepatitis B (HBV) and hepatitis A (HAV). All serum samples tested were reproducibly and consistently negative for anti-HTLV-III/LAV. Peripheral blood monocytes from both KS and PCL patients showed profound depression of chemotaxis; similarly all tumour patients gave markedly depressed cutaneous reactivity to tuberculoprotein and uniformly exhibited seropositivity to CMV, EBV, HBV and HAV. A great majority showed evidence of infection with Candida albicans. It is concluded that tropical African KS is not associated with HTLV-III/LAV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Fine-needle aspiration biopsy of pediatric neoplasms: correlation between electron microscopy and immunocytochemistry in diagnosis and classification.

A series of fine-needle aspiration biopsies performed in 635 children were reviewed. The diagnoses rendered in these patients included malignant lymphoma in 139 (21.9%); Hodgkin's disease, 25 (3.9%); neuroblastoma, 58 (9.1%); Wilms' Tumor, 37 (5.8%); Ewing's sarcoma, 32 (5.0%); rhabdomyosarcoma, 25 (3.9%); retinoblastoma, 22 (3.5%); leukemia infiltrate, 33 (5.2%); and miscellaneous tumors, 52 (8.2%). In 171 patients (26.9%), the biopsy was nondiagnostic. The cytomorphological characteristics of these lesions are briefly described and illustrated. Salient morphological features are further correlated with histological and ultrastructural appearances. Immunocytochemical patterns of these tumors are also discussed briefly.

Biopsy, Needle↗
PubMed2006

A phase II trial of intraperitoneal photodynamic therapy for patients with peritoneal carcinomatosis and sarcomatosis.

PURPOSE: A previous phase I trial of i.p. photodynamic therapy established the maximally tolerated dose of Photofrin (Axcan Pharma, Birmingham, AL)-mediated photodynamic therapy and showed encouraging efficacy. The primary objectives of this phase II study were to determine the efficacy and toxicities of i.p. photodynamic therapy in patients with peritoneal carcinomatosis and sarcomatosis. EXPERIMENTAL DESIGN: Patients received Photofrin 2.5 mg/kg i.v. 48 hours before debulking surgery. Intraoperative laser light was delivered to the peritoneal surfaces of the abdomen and pelvis. The outcomes of interest were (a) complete response, (b) failure-free survival time, and (c) overall survival time. Photosensitizer levels in tumor and normal tissues were measured. RESULTS: One hundred patients were enrolled into one of three strata (33 ovarian, 37 gastrointestinal, and 30 sarcoma). Twenty-nine patients did not receive light treatment. All 100 patients had progressed by the time of statistical analysis. The median failure-free survival and overall survival by strata were ovarian, 2.1 and 20.1 months; gastrointestinal cancers, 1.8 and 11.1 months; sarcoma, 3.7 and 21.9 months. Substantial fluid shifts were observed postoperatively, and the major toxicities were related to volume overload. Two patients died in the immediate postoperative period from bleeding, sepsis, adult respiratory distress syndrome, and cardiac ischemia. CONCLUSIONS: Intraperitoneal Photofrin-mediated photodynamic therapy is feasible but does not lead to significant objective complete responses or long-term tumor control. Heterogeneity in photosensitizer uptake and tumor oxygenation, lack of tumor specificity for photosensitizer uptake, and the heterogeneity in tissue optical properties may account for the lack of efficacy observed.

Adult↗
PubMed2005

[The therapeutic impact of (18)F-FDG whole body PET. A radiooncologist's view].

AIMS: An explorative analysis of the diagnostic as well as therapeutic impact of (18)F-FDG whole body PET on patients with various tumours in the setting of an university hospital radiation therapy was performed. PATIENTS AND METHODS: 222 FDG PET investigations (148 initial stagings, 74 restagings) in 176 patients with diverse tumour entities (37 lung carcinoma, 15 gastrointestinal tumours, 38 head and neck cancer, 30 lymphoma, 37 breast cancer, 19 sarcoma and 16 other carcinomas) were done. All PET scans were evaluated in an interdisciplinary approach and consecutively confirmed by other imaging modalities or biopsy. Unconfirmed PET findings were ignored. Proportions of verified PET findings, additional diagnostic information (diagnostic impact) and changes of the therapeutic concept intended and documented before PET with special emphasis on radiooncological decisions (therapeutic impact) were analysed. RESULTS: 195/222 (88%) FDG-PET findings were verified, 104/222 (47%) FDG-PET scans yielded additional diagnostic information (38 distant, 30 additional metastasis, 11 local recurrencies, 10 primary tumours and 15 residual tumours after chemoptherapy). The results of 75/222 (34%) scans induced changes in cancer therapy and those of 58/222 (26%) scans induced modifications of radiotherapeutic treatment plan (esp. target volumes). CONCLUSION: (18)F-FDG whole body PET is a valuable diagnostic tool for therapy planning in radiooncology with a high impact on therapeutic decisions in initial staging as well as in restaging. Especially in a curative setting it should be used for definition of target volumes.

Biopsy↗
PubMed1999

[An analysis of DNA content in 405 cases of human tumor by flow cytometry].

This study was intended to evaluate the relationship between the DNA content of cell cycle and the histology in human tumors. We detected the DNA content in 405 cases of fresh human tumor tissue by means of flow cytometry and observed the histology of tumor with light microscopy. The occurrences of aneuploidy in 22 cases of benign tumor and 383 cases of malignant tumor were 27% and 52% respectively. There were differences in aneuploidy in different histologic types of tumor. The aneuploidy in adenocarcinoma was about 50%, that in sarcoma was more than 37%, and that in squamous carcinoma less than 17%. S > or = 10, G2/m > or = 10 or S > or = 20, G2/m > or = 5 were present in malignant tumors, but were not found in benign tumors. The results suggest that there is obvious difference in the occurrences of aneuploidy in benign and malignant tumors and in different histologic type of tumor(P < 0.05). Benign and malignant tumor may be distinguished when SPF and G2/m reach a higher level (P < 0.01).

Carcinoma, Squamous Cell↗
PubMed1990

Replacement of the human insulin receptor transmembrane and cytoplasmic domains by corresponding domains of the oncogene product v-ros leads to accelerated internalization, degradation, and down-regulation.

Internalization, degradation, and insulin-induced down-regulation of insulin receptors were studied comparatively in transformed Chinese hamster ovary (CHO) cell lines, CHO.T and CHO.IR.ros, respectively expressing either the wild-type human insulin receptor (hIR) or a mutated hybrid receptor in which the transmembrane and cytoplasmic domains of hIR were replaced by corresponding domains of the transforming protein p68gag-ros (v-ros) of avian sarcoma virus UR2. At 37 degrees C, degradation of insulin receptors photoaffinity labeled on the cell surface (440 kDa) was most rapid for the hybrid hIR.ros (t1/2 1.0 +/- 0.1 h), intermediate for the wild-type hIR (t1/2 2.7 +/- 0.5 h), and slowest for the endogenous CHO insulin receptors (t1/2 3.7 +/- 0.7 h). Initial intracellular accumulation of the hIR.ros hybrid was also most rapid, reaching maximal amounts in 20 min following which the receptors disappeared rapidly from the intracellular compartment. In contrast, intracellular accumulation of the receptors in the CHO.T and CHO cells was slower, reaching maximal amounts in 60 min, and rapid disappearance of the receptors from the intracellular compartment did not occur. Chloroquine, a lysosomotropic agent, inhibited degradation of both the wild-type hIR and the chimeric hIR.ros and increased their intracellular accumulation. However, the chloroquine effect was much more marked for the hIR.ros receptors whose intracellular accumulation was increased by greater than 300% (in comparison with approximately 60% increase for the wild-type hIR), demonstrating marked intracellular degradation of the hybrid hIR.ros at chloroquine-sensitive sites. Insulin-induced down-regulation of the cell surface hIR.ros (52% loss in 3 h) was also more marked than the wild-type hIR (approximately 30% loss in 3 h). Thus, in the hybrid hIR.ros receptor, which was shown previously to exhibit insulin-stimulated autophosphorylation and kinase activity but not insulin-stimulated metabolic function, the capacity for internalization and down-regulation is not only preserved but is also markedly accelerated. These findings suggest that 1) the postreceptor coupling mechanisms mediating insulin-induced receptor internalization, degradation, and down-regulation are different from those mediating metabolic functions; and 2) v-ros may contain the structural information directing accelerated receptor catabolism.

Affinity Labels↗
PubMed2005

[Primary cutaneous extraskeletal Ewing's sarcoma].

BACKGROUND: Cutaneous extraskeletal Ewing's sarcoma is rare, being seen principally in children. We report a case of cutaneous sarcoma in the sole of the foot in a child. CASE REPORT: A 9-year-old child with no medical history of note was presenting a skin tumor for 3 months on the heel of the right foot. This tumor was burgeoning and painful and measured 3.5 cm in diameter; it was ulcerative at the surface and covered with a crust. Histological and immunohistochemical examinations confirmed the diagnosis of Ewing's sarcoma. Staging examinations proved negative and the patient underwent polychemotherapy, resulting in complete regression of the tumor. COMMENTS: Until 1998, 37 cases of cutaneous and subcutaneous Ewing's sarcoma were reported, being seen in 21 girls and 16 boys. Mean age at diagnosis was 15 years and mean tumor size was 3 cm (range: 1 to 12 cm). The tumors were observed throughout the body, being seen in the sole of the foot in 2 cases. Confirmation of the diagnosis was made by histological examination (malignant proliferation of small round cells in the dermis), immunohistochemical examination (CD99+) and cytogenetic analysis (translocation between chromosomes 22 and 11). The prognosis for cutaneous Ewing's sarcoma appears more favorable than that of Ewing's sarcoma in bone. Of the 37 patients treated, 7 had metastases and 2 presented relapse. Treatment for cutaneous Ewing's sarcoma, though not codified, consists of polychemotherapy associated with surgery and/or radiotherapy.

Age of Onset↗
PubMed2002

Expression of p53 gene product and cell proliferation marker Ki-67 in Ewing's sarcoma: correlation with clinical outcome.

Overexpression of tumor suppressor gene p53, cell proliferation nuclear antigen Ki-67, and proto-oncogene HER-2/neu are associated with poor prognosis in some tumors. We studied p53, Ki-67, and HER-2/neu immunohistochemical expression in archival biopsies of 37 patients with Ewing's sarcoma (ES). Patients with ES were treated at four Israeli hospitals between 1982 and 2000. Formalin-fixed paraffin-embedded tissue sections were stained by immunohistochemistry for p53, Ki-67, and HER-2/neu. More than 300 cells were counted on each slide, and the percentage of positively stained nuclei was computed. p53 overexpression was defined as nuclear staining of >2.3% of cells, Ki-67 overexpression as nuclear staining of >8.3% malignant cells. HER-2/neu staining was scored semiquantitatively on a scale of 0 to 4+. Twenty-two of 37 patients are alive and well, with mean follow-up time of 38 months. There was overexpression of p53 in 16 patients (43%) and of Ki-67 in 21 patients (57%). The correlation between p53 and Ki-67 overexpressions was 0.61. We found no overexpression of HER-2/neu. Median relapse-free survival (RFS) was statistically significantly shorter for patients with p53 overexpression (25 months) than for patients with negative staining (>92 months). The prognostic value of p53 overexpression was also significant after adjusting for tumor location and age. Median RFS was shorter for patients with positive Ki-67 staining (40 months) than for patients with negative staining (80 months) but did not reach statistical significance. Our study suggests that p53 is a predictor of RFS in patients with ES. More patients must be studied to assess the validity of this observation.

Adolescent↗