Analysis of Fas/CD95 gene somatic mutations in ovarian cancer cell lines.
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Apoptosis↗
Biomedical subjects
F Bertoni
Publications and source records attributed to F Bertoni.
Association of gastric and Waldeyer's ring lymphoma: a molecular study.
The coexistence of Waldeyer's ring and gastrointestinal non-Hodgkin's lymphomas at presentation is well known. Moreover, localized gastrointestinal relapses following successful treatment of lymphomas of Waldeyer's ring and thyroid lymphomas occurring after a prolonged disease-free interval have also been described. We report two cases of concomitant lymphoma in Waldeyer's ring and stomach. On the basis of the molecular analysis of the immunoglobulin heavy chain gene rearrangements, two different patterns of concomitant involvement by a lymphoma in Waldeyer's ring and in the gastrointestinal region seem to exist. One is represented by the preferential dissemination of the lymphoma from one site to the other, the second by the apparently independent growth of clonally unrelated lymphomas at each site.
Complementarity Determining Regions↗
Prognostic models for diffuse large B-cell lymphoma.
Prognosis of DLCL patients is variable and associated with well-defined risk factors. In the past decade several pretreatment variables have been incorporated into prognostic models to predict the death risk of individual patients. The International Prognostic Index (IPI), developed in an international consensus study, has been one of the most widely accepted of these models. In our study we applied some of the major prognostic models proposed for DLCLs in a cohort of 111 patients uniformly treated with a CHOP-like regimen in order to compare their sensitivity and specificity. We also evaluated the possibility of improving the IPI with the inclusion, from among the variables analysed, of serum beta-2 microglobulin level (beta-2M). The sensitivity, reflecting the ability to predict all failures in the cohort of patients as a whole, has improved from 45 to 73 per cent when the beta-2M-IPI model is compared with IPI, without a significant loss of specificity. Based on these results, the beta-2M-IPI may be useful for identifying the subset of patients with very poor prognoses. Therefore, the use of the serum beta-2M value in addition to the IPI may help in selection of the patients with DLCL at higher risk for treatment failure, and identification of those who may require specifically tailored therapeutic approaches.
Adult↗
Elastofibroma dorsi.
It is often difficult to identify the characteristics of soft-tissue tumors of the chest wall. This paper describes the peculiarities of elastofibroma dorsi, a rare pseudotumor of this site, to exclude many dangerous misconceptions. During the period between 1987 and 1997, we treated nine patients with elastofibroma dorsi. In six patients, the lesion was unilateral and in three it was bilateral. All these lesions were excised and no evidence of local recurrence or shoulder disability was observed at the last clinical evaluation. Elastofibroma dorsi is a rare, slow-growing, pseudotumoral lesion of the soft tissues of the chest wall with a peculiar radiographic and histologic pattern.
Aged↗
Eradication of Borrelia burgdorferi infection in primary marginal zone B-cell lymphoma of the skin.
Primary cutaneous B-cell lymphomas have been associated with Borrelia burgdorferi, the spirochete responsible for Lyme disease. Recently, cutaneous marginal zone B-cell lymphoma has been proposed as a distinct clinical-pathological entity. We report a case of primary cutaneous marginal zone lymphoma, associated with B burgdorferi infection. Polymerase chain reaction (PCR) amplification of the third complementarity determining region (CDR3) of the immunoglobulin heavy chain gene showed the presence of a monoclonal lymphoproliferation, therefore strengthening the histological diagnosis of a malignant process. B burgdorfer-specific hbb gene sequences were detected by PCR in the lymphoma tissue at diagnosis but not after antibiotic treatment. A nearly complete clinical and histological regression was observed after B burgdorferi eradication, with immunohistochemistry studies showing disappearance of plasma cell differentiation and a marked decline in the number of CD3+ T cells and Ki-67+ cells. Our case confirms the link between B burgdorferi and some cutaneous lymphomas. The disappearance of the microorganism accompanied by the unequivocal decrease of most indicators of active T- and B-cell immune response strongly supported a pathogenetic role for B burgdorferi in sustaining an antigen-driven development and growth of this cutaneous marginal zone lymphoma. Antibiotic therapy (analogous to Helicobacter pylori infection in gastric MALT lymphoma) might be helpful with the aim of averting or at least deferring the indication for more aggressive treatment.
Aged↗
Molecular detection of circulating neoplastic cells in patients with clinically localised gastric and non-gastric mucosa-associated lymphoid tissue lymphoma.
BACKGROUND: Unlike other low-grade lymphomas, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type usually presents with localised disease. AIM: To detect peripheral blood lymphoma involvement to establish the incidence of occult lymphoma dissemination. PATIENTS AND METHODS: In a series of 18 cases, peripheral blood was analysed by polymerase chain reaction, with primers directed to the third-complementarity determining region of the immunoglobulin heavy chain gene. RESULTS AND CONCLUSION: The presence of circulating neoplastic cells was detected in 21% of clinically localised cases. Moreover lymphoma cells were detected in 2 out of 6 morphologically normal bone marrow specimens. The present data show that, combining morphological and molecular methods, occult dissemination can be found in a large proportion of cases thus stressing the need for careful staging procedures. However, it has still to be clarified whether the presence of polymerase chain reaction-detectable circulating lymphoma cells can influence the outcome of mucosa-associated lymphoid tissue lymphoma patients submitted to antibiotic treatment (for gastric localisation) or local therapy (surgery or radiation, for non-gastric tumours).
Adult↗
Lack of CD95/FAS gene somatic mutations in extranodal, nodal and splenic marginal zone B cell lymphomas.
Germline CD95 (also known as FAS, APT1 and APO1) gene mutations have been associated with benign lymphoproliferative diseases and autoimmune processes. Somatic mutations have been reported in human tumours, including lymphomas. Since marginal zone B cell lymphomas usually arise in a background of chronic inflammation, often of autoimmune origin, we searched for CD95 gene mutations in an unselected series of marginal zone B cell lymphomas. The CD95/FAS full coding region, comprising exon-intron junctions, was amplified from genomic DNA by polymerase chain reaction (PCR) in 10 separate reactions. PCR products were analysed by single-strand conformation polymorphism (SSCP) and visualised by silver staining. Bands exhibiting an altered electrophoretic mobility were sequenced. Twenty-seven cases of marginal zone B cell lymphomas of whom fresh or frozen tumour material was available (18 extranodal, five splenic and four nodal) were studied. Previously described silent polymorphisms in exons 7 (C836T) and 3 (T416C) were detected in 42% and in 19% of the cases, respectively. One silent T-to-A substitution at bp 431, within exon 3, was found in one case. Our results did not reveal the presence of CD95 somatic mutations in unselected cases of marginal zone B cell lymphomas. On the basis of our data, we cannot rule out that other genes coding for proteins involved in the CD95-induced apoptotic pathway might be altered. However, this pathway does not seem to play an important role in the pathogenesis of these lymphoma subtypes.
Antigens, Neoplasm↗
BCL10 gene mutations rarely occur in lymphoid malignancies.
BCL10, a gene involved in apoptosis signalling, has recently been identified through the cloning of chromosomal breakpoints in extranodal (MALT-type) marginal zone lymphomas carrying the t(1;14)(p22;q32) translocation. BCL10 was also found mutated in these cases as well as in other types of lymphoid and solid tumors, suggesting that its inactivation may play an important pathogenetic role; however, this has been questioned by recent studies showing a lack of somatic mutations in human cancers. We report the mutation analysis of exons 1-3 of the BCL10 gene in DNAs from 228 cases of lymphoid malignancies (30 B cell chronic lymphocytic leukemias, 123 B and 45 T non-Hodgkin's lymphomas and 30 multiple myelomas). Somatic mutations were detected in four cases (approximately 2%): one small lymphocytic, one follicular and two diffuse large cell lymphomas. The mutations were all within exon 3 and have not been previously reported. Our data suggest that BCL10 mutations may play only a limited role in the pathogenesis of lymphoid neoplasms.
Adaptor Proteins, Signal Transducing↗
Endoscopic CO2 laser excision for tis, T1, and T2 glottic carcinomas: cure rate and prognostic factors.
We present the results of a retrospective study based on a cohort of 140 patients who underwent endoscopic CO(2) laser excision for previously untreated early glottic cancer (21 Tis, 96 T1, and 23 T2). This study used univariate analysis to review the impact on disease-free survival of 15 factors related to the host, the tumor, and the treatment. Recurrent cancer developed in 28 patients with an average interval to recurrence of 37.5 months. Retreatment consisted of different procedures, including laser excision, partial or total laryngectomy, and/or radiotherapy. The larynx was definitively preserved in 96% of patients. By the end of the study, 14 patients had died, but only 2 of them had died of the disease. Five-year overall survival and determinate survival were 93% and 98%, respectively. Ultimate local control at 5 years with CO(2) laser excision alone was 95% for Tis, 87% for T1, and 91% for T2 lesions. Only involvement of the anterior third of the vocal cord (P = 0.02), involvement of the false vocal cord (P = 0.02), and infiltration of the vocalis muscle (P = 0.004) showed a significant negative impact on disease-free survival.
Adult↗
Neoadjuvant chemotherapy for Ewing's sarcoma of bone in patients older than thirty-nine years.
The aim of this study was to determine whether the behaviour of Ewing's sarcoma of bone in adult patients is the same as that observed in children and adolescents. We reviewed the clinical features and outcomes of 23 patients over the age of 39 (17 males, 6 females) who had been treated with neoadjuvant chemotherapy between 1983 and 1995 at our institution. The most common primary sites of tumor were the extremities (16 cases); tumor volume was more than 100 ml in 17 patients, and elevated serum LDH levels were found in 6 cases. The local treatment was surgery in 8 cases, surgery plus radiotherapy in 8, and radiotherapy alone in 7 cases. Chemotherapy comprised a 4-drug regimen in 10 patients, while the other 13 patients received 6 drugs. At a follow-up of 8.8 years (3.5-15) 13 patients remained continuously free of disease and 10 relapsed. The 5-year disease-free survival and overall survival rates were 53% and 59%, respectively. Clinical features, dose intensity, and toxicity of chemotherapy, as well as the outcome of these 23 patients were found to be exactly comparable to the findings observed in 327 patients younger than 40 years treated at our institution in the same period, with the same therapy. We conclude that Ewing's sarcoma of bone in adults is no different from that occurring in children, and we therefore recommend the inclusion of all adult patients in multidisciplinary treatment trials of this tumor.
Adult↗
Dedifferentiated clear cell chondrosarcoma.
Dedifferentiation, a change in the histologic character and clinical behavior of a tumor to a more immature and aggressive one, occurs in approximately 11% of all chondrosarcomas. The original lesion is usually a low-grade chondrosarcoma. Clear cell chondrosarcoma is a rare cartilaginous tumor of low-grade malignancy with a preference for the ends of long bones. It is usually curable by resection. Recurrence commonly follows inadequate surgery, and metastases to lung, brain, and bones can develop. However, dedifferentiation has not yet been described in association with clear cell chondrosarcoma. Three patients are described who were initially diagnosed as having clear cell chondrosarcoma of the femur. Two were treated with en bloc resection for a clear cell chondrosarcoma. One of these had an undifferentiated sarcoma in a local recurrence after 6 years. In the second, metastasis of the clear cell chondrosarcoma developed 5(1/2) years after surgery; autopsy revealed undifferentiated sarcoma in the lung, heart, and lumbar spine. The third patient had dedifferentiated clear cell chondrosarcoma at the time of resection following the biopsy diagnosis of clear cell chondrosarcoma. All three died with metastatic disease. These three patients represent three different manifestations of dedifferentiation-at initial diagnosis, at recurrence, and at metastasis. To our knowledge, this is the first description of dedifferentiation occurring in clear cell chondrosarcoma.
Adenocarcinoma, Clear Cell↗
Prognostic factors in nonmetastatic Ewing's sarcoma of bone treated with adjuvant chemotherapy: analysis of 359 patients at the Istituto Ortopedico Rizzoli.
PURPOSE: The identification of prognostic factors in patients with nonmetastatic Ewing's sarcoma could allow the use of risk-adapted therapeutic strategies of treatment. PATIENTS AND METHODS: Data on 359 patients with nonmetastatic Ewing's sarcoma of bone treated at a single institution between January 1979 and April 1995 were retrospectively considered. The influence of clinical, hematologic, therapeutic, and histologic parameters on event-free survival was assessed. RESULTS: By univariate analysis, the following features were found to be associated with a poor prognosis: male sex (P <.02), age older than 12 years (P <.006), fever (P <.0001), anemia (P <.0025), high serum lactate dehydrogenase (LDH) level (P <.0001), axial location (P <.04), radiation therapy only for local control (P <.009), type of chemotherapy regimen (P <.0001), and poor chemotherapy-induced necrosis (P <.001). After multivariate analysis, the adverse independent prognostic factors were male sex (P <.04), age older than 12 years (P <.001), fever (P <.0002), anemia (P <.02), high serum LDH level (P <.0003), axial location (P <.02), and type of chemotherapy regimen (P <.0003). When the multivariate analysis was restricted to surgically treated patients, the adverse independent prognostic factors were poor chemotherapy-induced necrosis (P <.0001), fever (P <.015), anemia (P <.02), and high serum LDH level (P <.025). CONCLUSION: The prognosis in cases of nonmetastatic Ewing's sarcoma is influenced by many different clinical and hematologic variables, all of which are to be considered when patients are being stratified according to the risk of relapse. In surgically treated patients, the most important prognostic factor is chemotherapy-induced necrosis.
Adolescent↗
Neoadjuvant chemotherapy for peripheral malignant neuroectodermal tumor of bone: recent experience at the istituto rizzoli.
PURPOSE: The results achieved in 44 patients with nonmetastatic peripheral neuroectodermal tumor (PNET) of bone treated with neoadjuvant chemotherapy are reported. PATIENTS AND METHODS: A six-drug regimen of chemotherapy (vincristine, doxorubicin, dactinomycin, cyclophosphamide, ifosfamide, and etoposide) was administered to all patients. Local treatment consisted of surgery in 20 patients, surgery followed by radiotherapy in 13, and radiotherapy only in 11. RESULTS: At a mean follow-up of 4.5 years (range, 2 to 7 years), 23 patients (52%) remain event-free, 20 have relapsed (45%), and one has died of chemotherapy-related toxicity. The 5-year event-free survival and overall survival were 54.2% and 62.7%, respectively. To assess the prognostic significance of neural differentiation in the family of Ewing's sarcoma, these results have been compared with the outcomes of 138 concomitant patients with typical Ewing's sarcoma (TES) who were treated according to the same protocol. Of these, 103 (75%) remained continuously event-free, 34 (24%) relapsed, and one died of chemotherapy-related toxicity. It follows that PNET patients treated with this chemotherapy regimen have a significantly worse prognosis than typical ES patients (5-year event-free survival, 54.2% v 70.6%, P <.012; 5-year overall survival, 62.7% v 78.3%, P <.002). CONCLUSION: The authors conclude that studies into new adjuvant therapy for Ewing's sarcoma modulated according to risk of relapse should also consider neural differentiation as a risk factor.
Adolescent↗
Extranodal marginal zone B-cell lymphoma genotyping by Alu-polymerase chain reaction.
DNA amplification by polymerase chain reaction (PCR) with primers designed on the widely distributed Alu sequences allows the production of specific inter-Alu DNA-fingerprints. Amplification of tumour and matched normal DNA can show differences due to genetic alterations within the tumour genome. We applied this approach to study low-grade extranodal marginal zone B-cell lymphoma (of MALT type). After digestion with restriction enzymes, DNA samples were separately amplified by PCR with three different Alu-primers. A comparison between the fingerprint pattern from lymphoma and normal samples was made. Inter-Alu bands differing between the two samples were excised from the gel, cloned and sequenced. Nine cases of low-grade MALT-lymphomas have been analysed, giving seventeen different bands between tumour and normal. DNA sequence analysis showed identities for three of them with sequences available at the GenBank. The methodology of Alu-PCR to detect DNA-based abnormalities, in addition or combination with RNA-based methods, is a powerful tool to identify candidate regions frequently altered in tumours. With the increased available genomic sequences through the Human Genome Project, there will be an increasing probability of picking up perfect homologies with these sequences using cloned differential Alu-PCR bands in BLAST searches through genome databases.
Alu Elements↗
Secondary aneurysmal bone cyst simulating malignant transformation in fibrous dysplasia.
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Adult↗
Prevalence of Helicobacter pylori and hepatitis C virus infections among non-Hodgkin's lymphoma patients in Southern Switzerland.
BACKGROUND AND OBJECTIVE: Several recent studies have reported a high rate of previous hepatitis C virus (HCV) infection in patients with non-Hodgkin's lymphoma (NHL). However, it appears that there are marked geographical differences in the prevalence of HCV among NHL patients. There is further controversy concerning a possible pathogenetic link between HCV and certain histologic lymphoma subtypes, in particular MALT lymphomas, and it has recently been speculated that HCV might be involved in the multistep process of gastric lymphoma genesis, in addition to the well established role of chronic Helicobacter pylori infection. The aim of this study was to investigate the prevalence of HCV and H. pylori infections in patients with B-cell NHL in Southern Switzerland. DESIGN AND METHODS: One hundred and eighty newly diagnosed HIV-negative B-cell NHL patients, consecutively seen at a referral oncology center in Southern Switzerland between 1990 and 1995 were prospectively studied. A microparticle enzyme immunoassay was used to detect antibodies to HCV. Serologic determination of HCV genotype was done by the Murex method. The quantitative detection of IgG anti-H. pylori was performed by the Biorad GAP test. RESULTS: Infection with HCV was detected in 17/180 patients (9.4%; 95% C.I., 6%-15%). This prevalence is significantly higher than that observed in a large survey of 5424 new blood donors from the same area tested in 1992-97 (0.9%; 95% C.I., 0.7-1.2). Neither histologic subtypes nor specific extranodal presentations of NHL were associated with a higher prevalence of HCV. HCV serotype 2 (corresponding to genotypes 2a-c) was the most common. HCV infection was significantly associated with a shorter progression-free survival at both univariate and multivariate analysis. Anti-Helicobacter antibodies were detected in 81/180 patients (45%; 95% C.I., 38%-53%) and H. pylori infection was significantly associated with the development of primary lymphomas of the stomach. INTERPRETATION AND CONCLUSIONS: A high prevalence of HCV infection was detected in NHL lymphoma patients and was associated with a shorter time to lymphoma progression. HCV infection was not correlated with primary gastric presentation or with MALT-type histology. Our findings further support the key role of H.pylori infection in the pathogenesis of primary gastric lymphoma of MALT-type. The possible role of HCV in the pathogenesis of NHL should be further investigated.
Aged↗
The effect of Rituximab on patients with follicular and mantle-cell lymphoma. Swiss Group for Clinical Cancer Research (SAKK).
BACKGROUND: Clinical activity of the anti CD-20 monoclonal antibody Rituximab has been reported in patients with follicular lymphoma (FL) and mantle-cell lymphoma (MCL). PATIENTS AND METHODS: 120 patients with bi-dimensionally measurable FL or MCL (R.E.A.L. Classification) were treated with Rituximab 375 mg/m2/week for 4 weeks. A central pathology review confirmed the diagnosis of FL in 76 of 78 and of MCL in 39 of 42 cases. The response was evaluated after 8 weeks and confirmed after 12 weeks from the start of treatment. RESULTS: The toxicity of the treatment was, as expected, grade 1-2 fever and rigors during the first infusion and mild asthenia during the treatment period. Serious adverse events, probably or possibly related to the study treatment, included four deaths (3 of cardiac origin, 1 caused by P. carinii pneumonia) and 10 further nonfatal cases, including a permanent agranulocytosis and one case of heart failure. Response rate at week 12 was 52% for FL and 22% for MCL. After treatment, the BCL-2 rearrangement disappeared in 15 of 29 blood but only in 5 of 23 bone marrow samples; BCL-1 disappeared in 5 of 12 blood and 0 of 7 bone marrow specimens, as determined by PCR. CONCLUSIONS: Rituximab is an active agent for the treatment of FL, while its efficacy is modest in MCL. The effect in reducing minimal residual disease is more pronounced on the blood than it is on the bone marrow.
Adult↗
Extraabdominal desmoid tumor. A study of 83 cases.
One hundred three patients with extraabdominal desmoid tumor were treated between 1970 and 1996 at the authors' institution. Among these, 15 patients were lost to followup and five were excluded because they had less than 1-year followup. The remaining 83 patients were followed up for a mean of 11.2 years. Thirty-seven (44.6%) patients experienced local recurrence on average 1.8 years after treatment. There was no difference in the incidence of recurrence between the two groups treated with surgery only (45.3%) or with adjuvant radiation therapy administered after inadequate surgical resection of the tumor margins (41.2%). Recurrence was not related to age, gender, and site. None of the 83 patients died of the disease. For recurrent but stable lesions, clinical observation alone may be considered.
Adolescent↗