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Immunocytochemical demonstration of neuron-specific enolase (NSE) in human lung cancers
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Bronchus and Lung T~nors. Wilson, T.S., McDowell, E M., Trump, B.F. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, U.S.A. Arch. Pathol. Lab. Med. 109: 621-628, 1985. Lung tumors of various types, fixed in 4% formaldehyde-l% glutaraldehyde, were stained for keratin proteins. The results were compared with previous ultrastructural evidence of intermediate filament bundles (IFBs), presumed to be keratin. Electron and light microscopic methods were largely complimentary and the results were in agreement in 79% of cases. Light miscoscopy was superior for demonstrating keratinizing foci containing numerous well-developed IFBs, whereas electron microscopy was superior when keratin filaments were sparsely distributed in cells throughout a tumor. Fetal and adult bronchial specimens were also studied. Normal adult bronchus, fixed in aldehydes, was unreactive but keratin was observed in similarly fixed bronchi that showed epidermoid metaplasia and/or intraepithelial carcinoma. Keratin was demonstrated in normal adult bronchi fixed in ethanol. Keratin was not observed in fetal lung until the 14th week of gestation, when it appeared in basal cells and a few colunmar cells of the larger bronchi. Thereafter, keratin progressively appeared in the more distal branches. As specimens from gestations of less than 14 weeks were fixed in aldehydes, the apparent lack of immunoreactivity may have been artifactual. Nevertheless, keratin was demonstrable in aldehyde-fixed fetal bronchi at 16 and 23 weeks' gestation.
lmnunocytochemical Demonstration of NeuronS p e c i f i c Enolase (NSE) i n H~.an Lung Cancers. Bergh, J., Esscher, T., Steinholtz, L. et al. Department of Pathology, University of Uppsala, Uppsala, Sweden. Am. J. Clin. Pathol. 84: 1-7, 1985. An anti-serum against human neuronspecific enolase (NSE), raised in sheep, has been characterized and used for immunocytochemical localization of NSE in paraffin sections of normal tissues and lung cancers. Of the small cell carcinomas (SCC), 69 out of 99 (70%) cases stained with the anti-serum. Maltreated biopsies showed a lower frequency of positive staining (19/39), indicating the importance of well-preserved biopsies. There was no clear difference in the staining between the oat cell and intermediate cell type of SCC. A majority (14 out of 21) of the non-SCC's (large cell, adenocarcinoma and squamous cell carcinoma) were also stained by the anti-serum. Generally,
this staining was weak and it could be blocked by preabsorption of the anti-serum by purified NSE. It is concluded that NSE expression, in conjunction with traditional histology, serves as a useful but not exclusive marker for SCC,
Histochemical Studies of Dense-Core Granulated T~nors of the Lung. Neuron-Specific En01ase as a ~ r k e r for Granulated Cells. Wilson, T.S., McDowell, E.M., Marangos, P.J., Trump, B.F. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, U.S.A. Arch. Pathol. Lab. Med. 109: 613-620, 1985. It is well known that carcinoid tumors and some small-cell carcinomas of the lung contain densec6re granules (DCGs). Moreover, a small number of tumors presenting with epidermoid, large-cell, or adenocarcinoma histologic characteristics (so-called atypical endocrine tumors), also contain DCGs. Herein, we describe certain histochemical features of DCG tumors and compare them with other major lung tumor types that lack DCGs (non-DCG tumors). All DCG tumors contained neuron-specific enolase and many contained serotonin. These markers were not present in any non-DCG tumor. Other histochemical markers (glycogen, mucosubstances, corticotropin, betahuman chorionic gonadotropin, keratin, somatostatin, and calcitonin) were found in a proportion of DCG and non-DCG tumors, but were, in general, more common in non-DCG tumors and atypical endocrine tumors than in carcinoids and small-cell carcinomas. Alpha-fetoprotein was rarely found in non-DCG tumors, and was never observed in DCG tumors. The atypical endocrine group represents a class of tumors with a remarkably mixed and varied phenotype. Their potential significance is discussed and methods to facilitate their diagnosis are suggested.
The U l t r a s t r u c t u r e of Small Cell Lung Carcinoma i n Bronchial Biopsy Specimens. Elema, J.D., Keuning, H.M. Department of Pathology, University of Groningen, 9713 EZ Groningen, Netherlands. Hum. Pathol. 16: 1133-1140, 1985. Forty-three bronchial biopsy specimens from patients with small cell lung cancer (SCLC) were studied by electron microscopy. In 38 specimens the diagnosis was based on the light microscopic examination of Epon-embedded tissue; 36 of these specimens contained dense-core granules on electron microscopic examination. In five cases the light microscopic diagnosis was either different from the electron microscopic diagnosis or in doubt. Electron microscopy revealed dense-core granules as the only sign of differentiation, and the diagnosis was changed to SCLC. The tumor cell populations in the biopsy specimens were quite heterogeneous. Cells of the oat cell type were always present and, on electron microscopic examination, always showed degenerative changes. It was therefore decided that this cell type represents an artifact. The true SCLC tumor cell, which constitutes only a small portion of the tumor in biopsy specimens, is characterized by a regular oval or rounded cell with pale cytoplasm and a ground-
Bronchus and Lung T~nors. Wilson, T.S., McDowell, E M., Trump, B.F. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, U.S.A. Arch. Pathol. Lab. Med. 109: 621-628, 1985. Lung tumors of various types, fixed in 4% formaldehyde-l% glutaraldehyde, were stained for keratin proteins. The results were compared with previous ultrastructural evidence of intermediate filament bundles (IFBs), presumed to be keratin. Electron and light microscopic methods were largely complimentary and the results were in agreement in 79% of cases. Light miscoscopy was superior for demonstrating keratinizing foci containing numerous well-developed IFBs, whereas electron microscopy was superior when keratin filaments were sparsely distributed in cells throughout a tumor. Fetal and adult bronchial specimens were also studied. Normal adult bronchus, fixed in aldehydes, was unreactive but keratin was observed in similarly fixed bronchi that showed epidermoid metaplasia and/or intraepithelial carcinoma. Keratin was demonstrated in normal adult bronchi fixed in ethanol. Keratin was not observed in fetal lung until the 14th week of gestation, when it appeared in basal cells and a few colunmar cells of the larger bronchi. Thereafter, keratin progressively appeared in the more distal branches. As specimens from gestations of less than 14 weeks were fixed in aldehydes, the apparent lack of immunoreactivity may have been artifactual. Nevertheless, keratin was demonstrable in aldehyde-fixed fetal bronchi at 16 and 23 weeks' gestation.
lmnunocytochemical Demonstration of NeuronS p e c i f i c Enolase (NSE) i n H~.an Lung Cancers. Bergh, J., Esscher, T., Steinholtz, L. et al. Department of Pathology, University of Uppsala, Uppsala, Sweden. Am. J. Clin. Pathol. 84: 1-7, 1985. An anti-serum against human neuronspecific enolase (NSE), raised in sheep, has been characterized and used for immunocytochemical localization of NSE in paraffin sections of normal tissues and lung cancers. Of the small cell carcinomas (SCC), 69 out of 99 (70%) cases stained with the anti-serum. Maltreated biopsies showed a lower frequency of positive staining (19/39), indicating the importance of well-preserved biopsies. There was no clear difference in the staining between the oat cell and intermediate cell type of SCC. A majority (14 out of 21) of the non-SCC's (large cell, adenocarcinoma and squamous cell carcinoma) were also stained by the anti-serum. Generally,
this staining was weak and it could be blocked by preabsorption of the anti-serum by purified NSE. It is concluded that NSE expression, in conjunction with traditional histology, serves as a useful but not exclusive marker for SCC,
Histochemical Studies of Dense-Core Granulated T~nors of the Lung. Neuron-Specific En01ase as a ~ r k e r for Granulated Cells. Wilson, T.S., McDowell, E.M., Marangos, P.J., Trump, B.F. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, U.S.A. Arch. Pathol. Lab. Med. 109: 613-620, 1985. It is well known that carcinoid tumors and some small-cell carcinomas of the lung contain densec6re granules (DCGs). Moreover, a small number of tumors presenting with epidermoid, large-cell, or adenocarcinoma histologic characteristics (so-called atypical endocrine tumors), also contain DCGs. Herein, we describe certain histochemical features of DCG tumors and compare them with other major lung tumor types that lack DCGs (non-DCG tumors). All DCG tumors contained neuron-specific enolase and many contained serotonin. These markers were not present in any non-DCG tumor. Other histochemical markers (glycogen, mucosubstances, corticotropin, betahuman chorionic gonadotropin, keratin, somatostatin, and calcitonin) were found in a proportion of DCG and non-DCG tumors, but were, in general, more common in non-DCG tumors and atypical endocrine tumors than in carcinoids and small-cell carcinomas. Alpha-fetoprotein was rarely found in non-DCG tumors, and was never observed in DCG tumors. The atypical endocrine group represents a class of tumors with a remarkably mixed and varied phenotype. Their potential significance is discussed and methods to facilitate their diagnosis are suggested.
The U l t r a s t r u c t u r e of Small Cell Lung Carcinoma i n Bronchial Biopsy Specimens. Elema, J.D., Keuning, H.M. Department of Pathology, University of Groningen, 9713 EZ Groningen, Netherlands. Hum. Pathol. 16: 1133-1140, 1985. Forty-three bronchial biopsy specimens from patients with small cell lung cancer (SCLC) were studied by electron microscopy. In 38 specimens the diagnosis was based on the light microscopic examination of Epon-embedded tissue; 36 of these specimens contained dense-core granules on electron microscopic examination. In five cases the light microscopic diagnosis was either different from the electron microscopic diagnosis or in doubt. Electron microscopy revealed dense-core granules as the only sign of differentiation, and the diagnosis was changed to SCLC. The tumor cell populations in the biopsy specimens were quite heterogeneous. Cells of the oat cell type were always present and, on electron microscopic examination, always showed degenerative changes. It was therefore decided that this cell type represents an artifact. The true SCLC tumor cell, which constitutes only a small portion of the tumor in biopsy specimens, is characterized by a regular oval or rounded cell with pale cytoplasm and a ground-