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Immunohistochemical analysis of normal and mutated ras oncogene p21 expression in human pulmonary and pleural neoplasms.

In this study we examined 214 cases of primary human pulmonary neoplasms for the expression of a mutated form of the ras oncogene p21 product, recognized by the monoclonal antibody (MCA) DWP. Adjacent serial sections from these same cases had previously been used to demonstrate the frequency of ras p21 expression using the broadly reactive anti-ras p21 MCA RAP-5. Confirmation of the increased expression of p21 was accomplished using MCA Y13-259. The use of adjacent tissue sections from these cases allows the direct comparison of the expression of the mutated and non-mutated forms of ras p21. If reactivity with DWP would prove to be significantly more restrictive than that of the "pan" ras MCAs, RAP-5 and Y13-259, it would lend support to the possibility that DWP (and similar MCAs which detect other specific mutations) could be used to define subsets of these neoplasms based on their specific ras p21 phenotype. Since one would anticipate that the valine/cysteine substitution at position 12 of the ras p21 would occur at only low frequencies in human tumors, our results with DWP are consistent with this hypothesis. As previously reported, RAP-5 reacted with a high proportion of lung tumors (100/214 or 47%). In this report, we demonstrate the selective expression of the mutation recognized by the MCA DWP in only 5% of these same tumors (13/214), and that the expression of this mutated form is not restricted to any of the conventional histological subclasses of pulmonary neoplasms.

Antibodies, Monoclonal

Immunohistochemical evaluation of ras oncogene expression in pulmonary and pleural neoplasms.

We undertook an immunohistochemical analysis of human bronchopulmonary epithelial neoplasms and pleural mesotheliomas using a monoclonal antibody which recognizes ras oncogene products (p21ras). The monoclonal antibody, RAP-5, recognizes both unaltered and certain mutated p21ras. Formalin fixed and paraffin embedded tissue samples of 187 lung epithelial tumors and 27 pleural mesotheliomas were investigated; normal and bronchiectatic lungs were similarly studied. Normal lung and pleural tissue did not immunostain except for occasional type II pneumocytes. Reactive type II pneumocytes adjacent to carcinomas and bronchiectasis immunostained consistently. Twenty four/34 (71%) squamous carcinomas immunostained. Only 8/50 (16%) adenocarcinomas immunostained focally and weakly whereas 19/24 (79%) bronchioloalveolar carcinomas immunostained. Eleven/18 (61%) large cell carcinomas immunostained with variable intensity. Eleven/13 (85%) carcinoids, 6/7 (85%) well differentiated neuroendocrine carcinomas, and 18/21 (86%) intermediate cell neuroendocrine carcinomas immunostained while none of 20 small cell neuroendocrine carcinomas immunostained. Only a few mesotheliomas were immunostained focally. Two/14 (14%) epithelial type and 1/9 (11%) biphasic type mesotheliomas immunostained weakly; none of 4 spindle cell mesotheliomas immunostained. We conclude that while at least occasional cases of most types of pulmonary epithelial neoplasms express p21ras, the frequency and intensity of the expression are distinctly greater in certain tumor types such as squamous, bronchioloalveolar, and neuroendocrine neoplasm except for the small cell type. Contrary to these lung epithelial neoplasms, most mesotheliomas did not immunostain for p21ras. Whether the enhanced p21ras expression may point to a different mechanism of transformation or may merely reflect differentiation features remains undetermined.

Histocytochemistry

Immunohistochemical analysis of pulmonary and pleural neoplasms using a monoclonal antibody (47D10) which reacts with nonspecific cross-reacting antigen.

A series of 251 human pulmonary carcinomas were analyzed immunohistochemically for the antigens recognized by a new monoclonal antibody (MAb) 47D10. These antigens are part of a complex family of substances similar to, yet distinct from carcinoembryonic antigen (CEA), and are termed 'nonspecific cross-reacting antigens' (NCAs). The NCA epitope recognized by the MAb 47D10 is expressed on the cell surface and has previously been shown to be distinct from epitopes detected by several anti-CEA MAbs, as well as by MAbs 19-9 and Du-PAN-2. The NCA epitope recognized by MAb 47D10 is well preserved in formalin-fixed and paraffin-embedded tissues. Using immunohistochemistry, this epitope has been shown to have a limited biodistribution in normal tissues, and to be expressed by adenocarcinomas arising in the pancreas, colon, breast, ovary, prostate and lung. The frequency and pattern of NCA expression in human pulmonary neoplasms was found to correlate with the known distribution of CEA: and was often present in the non-small-cell carcinomas. In addition, the expression of CEA relative to NCA was evaluated in a select group of non-small-cell carcinoma cases using several anti-CEA MAbs, to directly compare the expression of CEA to NCA. In general, the NCA reaction pattern is more intense and expressed on more cells within the tumors than that of CEA expression.

Antibodies, Monoclonal

[Pleural pressure during thoracocentesis in patients with pleural neoplasms].

In 45 patients with cancerous pleural effusion, thoracocentesis was performed according to the following technique : after local anaesthesia (5 ml of 2% lidocaine) in the posterior part of the 6th intercostal space, thoracocentesis was carried out with a blunt trocar connected to a water manometer. The pleural pressure was measured before removal of the fluid (Po). Then three different techniques of drainage (active suction at -- 80 or -- 40 mmHg or underwater sealed drainage) were randomized. Pleural pressure was measured after removal of every 100 ml and at the end of the procedure (PT). The mean Po +/- SD was respectively -- 4.08 +/- 2.95, -- 3.81 +/- 3.12 and -- 2.53 +/- 2.42 cmH2O for the three different groups of drainage. After drainage, PT was decreased in the three groups, especially after -- 80 mmHg aspiration. In 14 patients, side effects occurred during thoracocentesis and the procedure was stopped. Symptoms, chiefly cough, occurred after a mean removal of 1.1 +/- 0.7 1. PT in these patients was statistically lower (-- 18 +/- 5.59 cmH2O) than in the 31 asymptomatic patients (--11.40 +/- 5.75 cmH2O) (p less than 0.001). In conclusion, the assessment of the pleural pressure during thoracocentesis seems to be convenient in order to prevent any complication of pleural evacuation : pleural evacuation should be stopped if the pleural pressure decreased below -- 18 cmH2O. A depression at -- 80 mmHg is too dangerous for pleural aspiration; -- 40 mmHg or under water sealed drainage are both convenient for a safe and complete evacuation.

Aged

Smooth muscle tumours presenting as pleural neoplasms.

Five smooth muscle tumours presenting as pleural neoplasma are presented. The patients were three women and two men aged between 21 and 69 years (mean = 45 years). Clinically, one patient presented with chest pain, one with empyema and the other three were asymptomatic. Two of the tumours were located in the left side of the chest cavity and three in the right side. In four cases, the lesions presented as solitary pleural-based masses that varied in size from 10-18 cm in greatest dimension: in two of these cases, involvement of the diaphragm was present in addition to the pleural involvement. In one case, the tumour was seen to totally encase the right lung simulating the growth pattern of malignant mesothelioma. Histologically, three cases displayed an atypical spindle cell proliferation with marked cellular pleomorphism, mitoses and areas of hemorrhage and necrosis. The other two cases were characterized by a bland-appearing smooth muscle proliferation of uncertain malignant potential composed of elongated cells with a moderate amount of eosinophilic cytoplasm and cigar-shaped nuclei, lacking significant nuclear pleomorphism or mitotic activity. Immunohistochemical studies showed strong positivity for alpha-smooth muscle actin in all cases, and for desmin in four of five cases, and a focal positive reaction for keratin in one case. Ultrastructural examination in one of the high-grade tumours showed features of smooth muscle differentiation. Three of the patients were treated by complete surgical excision while, in the other two patients, the lesions were incompletely resected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Cisplatin and cytosine arabinoside (ARA-C) for the therapy of primary and secondary pleural neoplasms].

15 patients with primary or metastatic pleural effusion were studied: 2 had diagnosis of malignant mesothelioma and 13 of metastatic pleural disease. The treatment used was based on in vitro and in vivo studies which show a synergy between ARA-C and Cisplatin. These drugs were instilled in pleural cavity at the dose of 100 mg./m2 for Cisplatin and 100 mg. for ARA-C. The cavity was drained after 4 hours. The treatment was repeated weekly. All patients had not been previously treated with loco-regional therapy. The response rate was 93% with 10 loco-regional complete remissions (66%). The two patients with malignant mesothelioma achieved a complete remission. The overall toxicity was acceptable. We conclude that combination of Cisplatin and ARA-C is well-tolerated and produces a very high response rate in the treatment of malignant pleural effusions.

Adult

[Primary malignant pleural neoplasms. Diagnostic code 163.09].

The code 163.09 indicates a primary malignant pleural neoplasma-malignant mesothelioma. We have reinvestigated 173 patients, who were discharged from a department of pulmonary medicine with this code number during a 8 1/2 year period. A revision during which repeated biopsies, course of the disease and, in some cases, autopsy were considered, revealed that 63 were confirmed as having a malignant mesothelioma, 94 had neoplastic disease secondary to malignancy elsewhere, 13 had benign changes and in three cases the records were missing. Malignant mesothelioma entitles the patient to compensation if he has worked with asbestos. An occupational history was present in 94% of those suffering from mesothelioma and in 71% of the remaining patients. Among patients with mesothelioma a history of asbestos exposure was obtained in 44%, a history of no exposure in 22% and no specific mention of asbestos in 34%. In the group of patients who did not have mesothelioma 14% had known exposure to asbestos, eight none and in 78% no specific information concerning asbestos was available. Twenty-three of the 63 patients with mesothelioma had been notified to the workmens' compensation board. Retrospectively, we found that 12 more patients should have been notified. Eight patients who did not fulfil the criteria for malignant mesothelioma had erroneously been notified to the board for compensation. We find that code 163.09 frequently has been used as a working diagnosis, which could not invariably be substantiated. Although malignant mesothelioma had been suspected, previous history concerning asbestos exposure was often incomplete or absent. A correct occupational history and aggressive bioptical procedures are essential in all cases where malignant mesothelioma is suspected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Immunohistochemical analysis of pulmonary and pleural neoplasms with monoclonal antibodies B72.3 and CSLEX-1.

Sequential paraffin sections of 222 epithelial lung tumors comprising all common histologic types, and 31 pleural mesotheliomas of all variants were immunostained with monoclonal antibodies (Mabs) B72.3 and CSLEX-1. Reactivity with Mabs B72.3 and CSLEX-1 respectively was noted in 7/57 and 4/57 squamous carcinomas, in 44/70 and 60/70 adenocarcinomas, 9/16 and 11/16 bronchioloalveolar carcinomas, 8/25 and 14/25 large cell undifferentiated carcinomas, 3/3 and 3/3 adenosquamous carcinomas, 0/11 and 0/11 carcinoids, 0/10 and 2/10 well differentiated neuroendocrine (NE) carcinomas, 4/13 and 5/13 intermediate cell NE carcinomas, 0/17 and 0/17 small cell NE carcinomas, and 0/31 and 1/31 mesotheliomas. In most instances, both Mabs stained the same tumors; however, reactivity with CSLEX-1 was more intense and extensive, and involved more cases. Therefore, regardless of conventional histologic type, staining with Mabs B72.3 and CSLEX-1 defines 4 subsets of lung tumors: one expressing both antigens, two expressing one but not the other, and one expressing neither. The possible biological and/or clinical significance of these subsets remains undetermined. When correlated with conventional histologic tumor types, our findings indicate: 1). both of these Mabs recognize most but not all adenocarcinomas and bronchioloalveolar carcinomas, and since CSLEX-1 stained more cases than B72.3, it may be argued that the former is a broader exocrine phenotype marker than the latter; 2). both of these Mabs select exocrine subsets of large cell undifferentiated carcinomas; 3). both of these Mabs stain exocrine cell subpopulations in well differentiated and intermediate cell NE carcinomas but not in carcinoids or small cell NE carcinomas, and 4). except for rare cases, neither B72.3 nor CSLEX-1 reacts with mesotheliomas regardless of variant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

Solitary fibrous tumor.

First described as a pleural neoplasm, the solitary fibrous tumor has been reported in a number of extrapleural sites, including the upper respiratory tract. The neoplasm is of mesenchymal origin, exists in benign and malignant forms, and is a histopathologic diagnosis made after exclusion of other soft tissue neoplasms. None of the eight reported sinonasal and nasopharyngeal solitary fibrous tumors have been histologically or biologically malignant. Surgical excision appears to control the tumor at these sites.

Adult