Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue.

BACKGROUND: DNA sequences and immunoreactivity associated with Simian virus 40 transforming factors, large T and small t antigens (SV40LTAg), suggestive of an aetiopathogenetic link have been identified in fresh frozen tissue of a high proportion of recent cases of pleural mesotheliomas from the United States, Italy and Germany. SV40 is not normally infective in man though it can transform human cells in tissue culture. A large cohort of people in the western world was accidentally parenterally inoculated with live SV40 through contaminated polio vaccines given between 1959 and 1961, and this might be a factor in the current continuing rise in the incidence of mesothelioma in the United States, Britain and Europe. The present study investigated the presence of SV40LTAg DNA in recently diagnosed cases of mesothelioma in Britain and the feasibility of detecting the SV40 DNA in archival tissue for retrospective analysis of cases in the peri-vaccination period. METHODS: DNA was extracted from fresh frozen and/or rehydrated formalin fixed, paraffin embedded tissue sections from nine recently diagnosed cases of mesothelioma, nine cases of pulmonary adenocarcinoma, and three reactive pleurae, and amplified by the polymerase chain reaction (PCR) using the primer pairs used previously on fresh frozen tissues-namely, the SV primer set directed at the LTAg gene sequence unique to SV40 and the PYV primer set directed at a sequence shared by SV40 and papovavirus strains BK and JC, respectively. RESULTS: PCR positivity with the SV primer set was restricted to four of the nine cases of mesothelioma. In contrast, six of the nine mesotheliomas, two of the nine adenocarcinomas, and one of the three reactive pleurae showed positivity with the PYV primers. The fresh frozen and corresponding formalin fixed, paraffin embedded tissue results concorded well with each other. CONCLUSIONS: Our data provide evidence for the association of SV40LTAg primer specific DNA with human pulmonary mesothelioma in the British population.     

Telomerase activity in human pleural mesothelioma

BACKGROUND: Gradual telomere erosion eventually limits the replicative life span of somatic cells and is regarded as an ultimate tumour suppressor mechanism, eliminating cells that have accumulated genetic alterations. Telomerase, which has been found in over 85% of human cancers, elongates telomeres and may be required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in pleural malignant mesothelioma, which may be the target for future anti-telomerase drugs. METHODS: Telomerase activity was semiquantitatively measured in extracts from 22 primary pleural mesotheliomas, two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six short term mesothelial cell cultures from normal pleura using a non-isotopic dilution assay of the telomeric repeat amplification protocol. RESULTS: Twenty of the 22 primary mesotheliomas (91%) and all tumour derived mesothelioma cell lines were telomerase positive. Different levels of enzyme activity were observed in the tumours of different histological subtypes. Telomerase activity could not be detected in the six normal mesothelial cell cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed strong telomerase activity. CONCLUSIONS: Telomerase activity is found in a high proportion of mesotheliomas and anti-telomerase drugs might therefore be useful clinically. The results are consistent with the hypothesis that telomerase activity may be a feature of carcinogenesis in mesotheliomas and possibly in many other cancers.     

Malignant pleural mesothelioma

Malignant pleural mesothelioma carries a poor prognosis, for which no standard therapy has been established. We report 15 cases of malignant pleural mesothelioma experienced since 2000 focusing on their clinical features. They included 14 male and 1 female aged 38 to 81 (62.8 on average) years. All patients were diagnosed by pleural biopsy under thoracoscopic guidance. Histology of the pleural biopsy specimen showed epithelial mesothelioma in 8 patients, biphasic mesothelioma in 3, sarcomatous mesothelioma in 2 and desmoplastic malignant mesothelioma (DMM) in 2. Twelve patients received chemotherapy. Of these, 3 were followed by surgery. In addition to 2 of these 3 patients, 2 underwent extrapleural pneumonectomy (EPP) without adjuvant treatment. Remaining 1 received palliative treatment only. As a result, 6 patients are surviving, 7 died of primary diseases and 2 died of other diseases. The longest survival time with chemotherapy is 41 months in a surviving patient with epithelial mesothelioma and that with EPP is 25 months in a surviving patient with DMM. The 2-year survival rate of the 14 patients was 44.4% and the median survival time in patients with epithelial mesothelioma was 30.6 months.     

Malignant pleural mesothelioma]

Malignant pleural mesothelioma is a severe disease closely associated with asbestos exposure, at work or environmental. Its incidence has risen for some decades and it's expected to peak between 2010 and 2020. Up today, no treatment has been demonstrated as effective in influencing disease-related survival and the median prognosis ranges between 9 and 17 months after the diagnosis. The epithelial subtype of the disease seems to have a better prognosis when early diagnosed and treated with intrapleural immunotherapy or multimodality therapy. The diagnosis of the disease, often by exclusion, is obtained after macroscopic sampling of the pathological tissue, best accomplished by thoracoscopy, which also allows the intracavitary evaluation of the extension of the disease. Chemotherapy and radiotherapy alone didn't demonstrate any efficacy on the patient survival. For the early-stage disease (stage I) a therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodality treatment combining surgery, radiotherapy and chemotherapy should be proposed. This multimodality protocol has proved to be effective in patients with epithelial subtype, negative margins of resection and negative lymph nodes.     

Expression of p21 in SV40 large T antigen positive human pleural mesothelioma: relationship with survival

BACKGROUND: Mesothelioma is the most commonly occurring primary pleural neoplasm. Several studies have documented an increase in the incidence of this malignancy during the last decades. Although the association between asbestos exposure and development of mesothelioma is generally accepted, the exact mechanism of carcinogenesis is unknown. Recently, Simian virus 40 large T antigen (SV40 Tag) expression has been detected in pleural mesothelioma. The ability of SV40 oncoproteins to inactivate p53 and retinoblastoma tumour suppressor proteins has been proposed as an important step in the pathogenesis of human mesothelioma. METHODS: To obtain a better understanding of the molecular mechanisms of the pathogenesis of mesothelioma, the expression of the cell cycle inhibitor p21(WAF1/CIP1) (p21), a downstream target of p53, was evaluated immunohistochemically in a group of 29 mesothelioma specimens already characterised for the presence of SV40 Tag sequences. RESULTS: Statistical analysis did not reveal any correlation between p21 expression and histopathological type of mesothelioma using the kappa(2) test (p=0.577). A significant positive relationship was found between p21 expression level and the patients' overall survival according to the Kaplan-Meier survival curves and using a log rank test (median difference in survival 7 months, 95% CI 4.8 to 9.9; p<0.001). CONCLUSIONS: Determination of p21 expression bears a prognostic significance in patients affected with mesothelioma, further underlining the role of SV40 in the pathogenesis of malignant pleural mesothelioma.     

Diffuse malignant pleural mesothelioma

Malignant pleural mesothelioma is an uncommon neoplasm that caused 647 deaths in Japan in 2004. The incidence of the disease is increasing and is estimated to reach its peak in 2025. We reviewed the clinical features in 11 consecutive patients with pathologically confirmed diffuse malignant pleural mesothelioma in our institution from January 1997 to December 2002. Of the 11 patients, 9 were male and 2 were female with a mean age of 66 (range, 55 to 90) years. Symptoms included dyspnea in 4 patients, chest pain in 3, dyspnea plus chest pain in 2, and cough in 2. Median period between symptom onset and presentation was 1 (range, 0 to 6) month. A history of asbestos exposure was identified in 3 patients and suspected in 5. A definitive diagnosis was made by closed pleural biopsy in 8 patients, pleural fluid cytology in 2, and autopsy in 1. Histological subtypes included epithelioid in 6 patients, sarcomatoid in 2, biphasic in 1, and unknown in 2. International Mesothelioma Interest Group (IMIG) staging included stage II in 6 patients, stage III in 3, and stage IV in 2. Median period between presentation and diagnosis was 1 (range, 0 to 22) month. Treatment included intrapleural chemotherapy in 4 patients, extrapleural pneumonectomy in 3, pleural drainage in 2, and best supportive care in 2. During the follow-up period, 9 patients died and 2 survived. Median survival time after diagnosis was 3 (range, 0 to 51) months. Of the 11 patients, 7 (64%) died within 6 months after the first presentation, and only 1 (9%) lived longer than 2 years after diagnosis.     

Localized malignant pleural mesothelioma

Localized malignant pleural mesothelioma (LMPM) is a rare tumor; previously only 52 cases have been reported in the English literature. This type of tumor should be distinguished from diffuse malignant pleural mesothelioma, because a good outcome may be obtained by surgical resection. We report a case of LMPM which grew rapidly within 1 year. Surgical resection was performed, and at present, 6 months since the operation, the patient remains free of the disease.     

Intradural pleural malignant mesothelioma

Summary Pleural malignant mesothelioma is a rare tumour of the pleural epithelium, which progresses by infiltration into the lung parenchyma, the chest wall, and the mediastinum. Haematogenous spreading may occur in the late stages of the disease. Spinal involvement is exceptional and usually occurs in the vertebral body or epidural space, and intradural location of a mesothelioma is even more uncommon. In this article, a MEDLINE literature review on intradural mesothelioma was conducted and four intradural mesothelioma cases in the English literature were retrieved: one in the intradural extramedullary location and three with intramedullary growth. Additionally, we report a 50-year-old patient with a pleural malignant mesothelioma that spreads across the dura into the spinal cord at T5.     

胸膜间皮瘤的诊断与治疗

经手术病理证实的胸膜间皮瘤１８例，其中良好性１５例，恶性１３例，局限型７例，弥漫型１１例。本病术前误诊率高，本组误诊８例。１９例均行手术治疗，术后３例失访。本病诊断主要依靠胸水的检查和胸膜活检；局限型胸膜间皮瘤一经确诊，主张早期手术；弥漫型确诊后如患者全身情况允许，应行广泛手术切除及术后综合治疗，以利于延长患者生命。     

Pleurectomy/decortication plus chemotherapy: outcomes of 40 cases of malignant pleural mesothelioma

Malignant pleural mesothelioma still has a dismal prognosis. Despite good patient selection and a multimodality approach, local disease control remains a problem. Whether submitted to pleurectomy/decortication or to extrapleural pneumonectomy, disease progression occurred in all 40 patients in this study. The role of radio-chemotherapy remains uncertain. Between 1985 and 2002, 40 patients underwent pleurectomy/decortication in combination with intracavitary chemotherapy. Pleurectomy was performed to remove all gross tumour, or to achieve significant debulking. Partial or total pleurectomy of the visceral pleura depended on the extent of the tumour. Systemic chemotherapy was administered when disease progression occurred. All 40 patients had disease progression, due in all cases to local recurrence. The Kaplan-Meyer method was used for statistical evaluation. Treatment was relatively well tolerated and quality of life satisfactory. Until disease progression, no important chest pain, pleural effusion, or dyspnoea occurred. Overall survival was 28% at 2 years and 17% at 3 years. Histological sub-type is the only significant prognostic factor for survival. Low morbidity and mortality and good quality of life after treatment make pleurectomy/decortication with intracavitary and systemic chemotherapy not only a radical approach in early stages, but also a good palliative treatment in advanced malignant pleural mesothelioma, especially in patients who are unsuitable for extrapleural pneumonectomy.     

Cytologic diagnosis of pleural mesothelioma

The efficacy of examination of various cytologic material in patients with mesothelioma was analysed. A total of 48 studies were carried out in 24 patients. Examination of transthoracic aspiration material obtained from the tumor and pleural cavity exudate yielded the best results. When mesothelioma of the pleura is suspected, care should be taken to collect material from different areas of the tumor, bearing in mind the significance of discovering different components of the tumor in it. On grounds of study of various cytologic material, a malignant tumor or adenocarcinoma was diagnosed in 43% and mesothelioma in 48% of patients.     

Localized malignant lymphohistiocytoid pleural mesothelioma

We report a case of a 42-year-old man with a right pleural mesothelioma. This neoplasm has 3 rare features. Firstly, it was a localized form: suspected by imaging, visualized by video-assisted thoracoscopy, at the time of the curative-thoracotomy and confirmed by the pathological analysis. The second characteristic is its histological type: "malignant lymphohistiocytoid mesothelioma". This rare subtype has been reported in only 4 papers. Third, after pleuro-pneumonectomy, our patient is alive after 6 years and 5 months postoperatively without any sign of recurrence. Only one case with a long follow-up has been reported but with recurrence at 5 years postoperatively.