Neural markers in carcinoma of the lung

Dhillon, Amar P.; Rode, J.; Dhillon, D P; Moss, E; Thompson, R.J.; Spiro, Stephen; Corrin, B.

doi:10.1038/bjc.1985.97

Cited by 46 publications

(20 citation statements)

References 20 publications

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“…Similar findings have been reported by others (Bergh et al, 1985;Said et al, 1985;Rode et al, 1985;Dhillon et al, 1985;Linnoila et al, 1988b;Graziano et al, 1989). The detection of CK-BB immunoreactivity in 67% of SCLC and 14% of squamous cell tumours compares well with previous radioimmunoassay data (Ruberry et al, 1983).…”

Section: Discussionsupporting

confidence: 80%

“…These include L-dopa decarboxylase (Baylin et al, 1980;Berger et al, 1981;Gazdar et al, 1988a), peptide hormones including calcitonin (Berger et al, 1981) and gastrin releasing peptide (Yamaguchi et al, 1985) and neurone specific enolase (NSE) (Bergh et al, 1985;Said et al, 1985;Rode et al, 1985;Dhillon et al, 1985;Linnoila et al, 1988b;Graziano et al, 1989). Although elevated levels of neuroendocrine (NE) markers have been detected in NSCLC tumours, the expression of more than one NE marker, though common in small cell lung cancer (SCLC) occurs much less frequently in NSCLC (Berger et al, 1981).…”

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confidence: 99%

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Neuroendocrine differentiation and clinical behaviour in non-small cell lung tumours

Sundaresan

Reeve²,

Stenning³

et al. 1991

Br J Cancer

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Summary The present study examines the relationship between neuroendocrine (NE) differentiation and the clinical behaviour of non-small cell lung cancer (NSCLC). Retrospective (n = 315) and prospective (n = 44) cohorts of non-small cell tumours were obtained from surgically treated cases of lung cancer, comprising 218 squamous cell carcinomas, 65 adenocarcinomas, 51 adenosquamous carcinomas, and 25 large cell undifferentiated carcinomas. Paraffin wax embedded and fresh frozen tissue sections were stained for the NE markers neurone specific enolase, creatine kinase-BB, bombesin, neurotensin, chromogranin A, synaptophysin and UJ-13A. The expression of two or more markers was observed in 30% of cases, and was taken to identify NE-NSCLC. A statistically significant correlation between nodal status and NE differentiation (P = 0.05), and disease stage and NE differentiation (P = 0.04) was observed. However, there was no correlation between NE differentiation and survival. These findings suggest that NE-NSCLC, analogous to SCLC is more highly metastatic than non-NE-NSCLC.

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Section: Discussionsupporting

confidence: 80%

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confidence: 99%

Neuroendocrine differentiation and clinical behaviour in non-small cell lung tumours

Sundaresan

Reeve²,

Stenning³

et al. 1991

Br J Cancer

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“…However i t became evident that patients with small cell lung carcinoma s well s patients with non-small cell lung carcinoma may exhibit high concentrations of γ-enolase in plasma or serum (3)(4)(5)(6)(7)(8)10). These results, confirmed by our measurements, possibly reflect some uncertainties in the exact histological classification, caused by mixed type carcinomas (24)(25)(26). Alternatively, during tumour progression, non small cell lung cancers cells could also develop the ability to produce γ-enolase isoenzymes s a result of de-differentiation processes.…”

Section: Discussionsupporting

confidence: 80%

“…γ-Enolase isoenzymes have also been detected immunohistochemically in neuroendocrine tumours (22,23), s well s in carcinomas of the lung (3,24,25). Carney and coworkers were the first (4) to use the determination of γ-enolases s a marker for assessing the extent of the disease, and response to therapy of small cell lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Enolase Isoenzymes as Tumour Markers

Kd¹,

Schumacher²,

Arnold³

et al. 1986

Clinical Chemistry and Laboratory Medicine

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Summary: a-and γ-enolase isoenzyme substance concentrations were measured in serum and plasma from healthy subjects and from 174 patients with different solid tumours. While α-enolase was found to be increased in the plasma of patients with tumours of quite different origin, γ-enolase apparently reflected malignancies of the neuroendocrine System. Before the beginning of the cytotoxic therapy γ-enolase was increased above the upper limit of the reference r nge (10 μg/l) in 27/27 patients (100%) suffering from small cell lung cancer. Most patients with squamous cell carcinoma of the lung or with prostatic cancer exhibited normal γ-enolase, while both tumour types produced high plasma substance concentrations of the aisoenzymes of enolase. Wertigkeit der Enolase-Isoenzyme als TumormarkerZusammenfassung: Die Substanzkonzentrationen von a-und γ-Enolase-Isoenzym wurden im Serum und Plasma von Gesunden und 174 Patienten mit unterschiedlichen, soliden Tumoren bestimmt. W hrend sich die α-Enolase-Formen als relativ unspezifisch, d. h. bei unterschiedlichen Tumoren im Plasma erh ht fanden, zeigten die γ-Isoenzyme maligne Erkrankungen des neuroendokrinen Systems relativ spezifisch an. Bei einem Kollektiv von 27 Patienten mit kleinzelligem Lungen-Karzinom fand sich vor der Therapie in 100% der F lle ein Anstieg der γ-Enolase ber den oberen Referenzwert (10 Hg/l). Patienten mit Plattenepithel-Karzinom der Lunge und solche mit Prostata-Karzinomen hatten in der Regel normale γ-Enolase-, dagegen erh hte aEnolase-Substanzkonzentrationen im Plasma. Introdiictionstudied and characterized by Marangos* group (2). Cells related to the amine precursor uptake and de-Recently it was found that small cell lung carcinoma carboxylation (APUD) System (1) share several com-cells also express APUD ceU-specific markers such s mon properties, which include the ability to produce bombesin, L-dopa decarboxylase and γ-enolase (3). and secrete peptides, the presence of storage vesicles The first report by Carney et al. (4) that γ-enolase is and a similar enzyine and isoenzyme pattern. One of elevated to a high degree in the serum of most small the marker proteinsforthis System is the γ-isoenzyme cell lung cancer patients was confirmed by others of enolase (neuron-specific enolase, NSE) extensively (5 -14), but it became evident that patients suffering

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“…However, more recently it has been found that immunostaining for neural markers, including NSE, is of little value in the positive identification of SCLC by endobronchial biopsy since a significant number of NSCLC tumours were positively stained for NSE (Dhillon et al, 1985). Furthermore, considerable intratumoral heterogeneity with respect to NSE immunostaining has also been observed in SCLC tumours, with some cells showing strong, and others little, staining (Dhillon et al, 1985;Wilson et al, 1985). Clearly the clinical usefulness of NSE as a diagnostic adjunct for the positive identification of SCLC is a matter of some controversy.…”

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confidence: 99%

Neuron specific enolase expression in carcinoma of the lung

Reeve¹,

Stewart²,

Watson³

et al. 1986

Br J Cancer

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Summary The value of neuron specific enolase (NSE) immunoreactivity as a marker for small cell lung cancer (SCLC) has been assessed using a monoclonal antibody (MCAB) against NSE. MCAB specificity was confirmed using purified enolase isoenzymes, sections of human brain, a panel of lung tumours, neuroendocrine and non-neuroendocrine tumours and normal tissues. Using this MCAB in radioimmunoassay and immunohistochemistry, NSE immunoreactivity was detected in all SCLC material examined. However, considerable reactivity was also observed in a number of non-small cell lung cancer cell lines and tumour biopsy specimens. Furthermore, intratumoral heterogeneity with respect to NSE immunostaining was observed in several cases. Factors which may underlie such intratumoral phenotypic diversity were assessed using flow cytometry together with MCABs directed against both NSE and non-neuronal enolase. Such studies revealed that enolase expression in cells which were no longer actively proliferating differed markedly from that of cells in exponential growth. Furthermore, cells grown under conditions of increasing hypoxia exhibited increased enolase expression relative to those grown under oxygenated conditions. It is concluded from these studies that NSE immunoreactivity per se is an unreliable marker for the SCLC phenotype.

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Neural markers in carcinoma of the lung

Cited by 46 publications

References 20 publications

Neuroendocrine differentiation and clinical behaviour in non-small cell lung tumours

Neuroendocrine differentiation and clinical behaviour in non-small cell lung tumours

Enolase Isoenzymes as Tumour Markers

Neuron specific enolase expression in carcinoma of the lung

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