creatine kinase b subunit as a biomarker for small cell carcinoma of the lung: comparison with...

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264 pertile 12124 U/1, range 1268-15280 U/1) were higher than in the bronchitis groxp (median 507 U/1, 16 percentile 96 U/l, 84 percentile 3498 U/l, range 84-3800 U/1). In seven patients with bronchial carcinoma ke- ratin was present in the bronchial lavage in concentrations between 0.2-1.2 mg/l. In addition, the connection between the pre- sence of free keratin in the bronchial la- vage and the expression of this protein in the cytoskeleton from tumour cells could be confirmed by showing that free keratin was also present in the culture medium of a bronchial tumour-cell line. Role of Biological Markers and Probes in Lung Carcinomas. Dorreen, M.S. Department of Respiratory Medicine, Royal Hallamshire Hospital, Sheffield SI0 2JF, U.K. Clin. Respir. Phy- siol. 22: 137-146, 1986. Bronchial carcinomas are frequently as- sociated with ectopic secretion of hormo- nes which may be responsible for paraneo- plastic syndromes. In non small cells carci- nomas, serum calcitonin levels may be rai- sed. Hypercalcaemia can be found in squamous carcinomas and secretion of hCG (respon- sible for gynaecomastia) in large cells carcinomas. In small cell carcinoma, many hor- mones (ACTH, MSH, ADH, calcitonin) can be produced; however, their serial measurements as well as that of the carcino-embyonic antigen add nothing to the information available with standard staging investi- gations. More recent studies have identified three proteins products: the BB-isoenzyme of creatine kinase, bombesin and neurone- specific enolase. The latter seems a prom~- sing marker to follow up the course of the disease. Tumour-associatedMarkers in Malignant Lung Cancers. Piancino, G., Racca, P., Rayneri, W. et al. Ospedale Maggiore S. Giovanni Battista, Torino, Italy. Minerva Med. 77: 19-25, 1986. The usefulness of assaying tumoral mar- kers in lung cancer is examined. 63 patients (56 men and 7 women) suffering from various types of malignant lung cancer were examined and compared with 44 patients hsopitalised for benign lung complaints. The markers used were CEA, Ferritin, GICA and TPA. Ferritin proved the most sensitive marker with 73% positive results for tumours as opposed to 47.6% for CEA and GICA and only 19% for TPA. The division of tumours into histological types (adenocarcinomas, squamous cell carci- nomas, microcytomas and large cell anapla- stic carcinomas) showed that Ferritin is the best marker for lung cancer (70% posi- tive results in adenocarcinomas and squa- mous cell carcinomas, 62.5% in microcytomas, 87.5% in large cell anaplastic carcinomas). ~Aand GICA display almost the same level of sensitivity in the different histological types: the sensitivity of TPA is low in all cases. Specificity was found to be satis- factory for all markers examined. It may be concluded that best results are obtained by combining the Ferritin assay with CEA and/or GICA tests. Evaluation of a Radioinmunoassay for Neuron Specific Enolase in Small Cell Lung Cancer. cooper, E.H., Splinter, T.A.W., Brown, D.A. et al. Unit for Cancer Research, University of Leeds, Leeds LS2 9JT, U.K. Br. J. Cancer 52: 333-338, 1985. A radioimmunoassay for neuron specific enolase (NSE), a marker of neuroendocrine differentiation, has been evaluated in small cell lung cancer (SCLC). In untreated patients 25/38 (68%) with localized SCLC had raised blood levels of NSE (>13 ng/ml ), in exten- sive disease 34/39 (87%) patients had raised NSE levels. In patients with non-small cell lung cancer (NSCLC) the serum levels were raised in 16/94 (17%). In extensive tumours of non-pulmonary origin NSE levels were increased in 24/116 (20%) patients. Longitu- dinal studies indicated a good correlation between the response to chemotherapy and fall of NSE levels. Tumour progression was accom- panied by a rising NSE in 25/29 patients~ with doubling times of 7-90 days. In patients with progression with a normal NSE the recur- rence was a NSCLC. Cerebral metastases oc- curring.as the only recurrence during clinical complete remission were not accompanied by a rise of NSE. Serum NSE levels provides a va- luable monitor for SCLC during and after chemo- therapy. Creatine Kinase B Subunit as a Biomarker for Small Cell Carcinoma of the Lung: Comparison with Ganmm-enolase. Kato, K., Ariyoshi, Y., Nakajima, T. Depart- ment of Biochemistry, Institute for Develop- ment Research, Aichi Prefectural Colony, Aichi 480-03, Japan. Jpn. J. Cancer Res., Gann 76: 1162-1167, 1985. Concentrations of creatine kinase (CK) B subunit (CK-B) in tumor tissues and in sera of patients with various lung carcinomas were determined, together with the concen- trations of neuron-specific gamma-enolase (gamma subunit of alphagamma and gammagamma enolases), by theuse of a sensitive enzyme immunoassay method. The CK-B and gamma-eno- lase levels were enhanced in tissues of small cell carcinoma of the lung. The average tis- sue contents of CK-B in small cell carcinoma (SCCL), adenocarcinoma (ADCL) and squamous cell carcinoma (ECCL) of the lung, and nor- mal lung were 2320, 308, 163, and 372 ng/mg protein, respectively. The contents of gamma- enolase in those tissues were 1460, 276, 225, and 42.7 ng/mg protein, respectively. Serum

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Page 1: Creatine kinase B subunit as a biomarker for small cell carcinoma of the lung: Comparison with gamma-enolase

264

pertile 12124 U/1, range 1268-15280 U/1) were higher than in the bronchitis groxp (median 507 U/1, 16 percentile 96 U/l, 84 percentile 3498 U/l, range 84-3800 U/1). In seven patients with bronchial carcinoma ke- ratin was present in the bronchial lavage in concentrations between 0.2-1.2 mg/l. In addition, the connection between the pre- sence of free keratin in the bronchial la- vage and the expression of this protein in the cytoskeleton from tumour cells could be confirmed by showing that free keratin was also present in the culture medium of a bronchial tumour-cell line.

Role of Biological Markers and Probes in Lung Carcinomas. Dorreen, M.S. Department of Respiratory Medicine, Royal Hallamshire Hospital, Sheffield SI0 2JF, U.K. Clin. Respir. Phy- siol. 22: 137-146, 1986.

Bronchial carcinomas are frequently as- sociated with ectopic secretion of hormo- nes which may be responsible for paraneo- plastic syndromes. In non small cells carci- nomas, serum calcitonin levels may be rai- sed. Hypercalcaemia can be found in squamous carcinomas and secretion of hCG (respon- sible for gynaecomastia) in large cells carcinomas. In small cell carcinoma, many hor- mones (ACTH, MSH, ADH, calcitonin) can be produced; however, their serial measurements as well as that of the carcino-embyonic antigen add nothing to the information available with standard staging investi- gations. More recent studies have identified three proteins products: the BB-isoenzyme of creatine kinase, bombesin and neurone- specific enolase. The latter seems a prom~- sing marker to follow up the course of the disease.

Tumour-associatedMarkers in Malignant Lung Cancers. Piancino, G., Racca, P., Rayneri, W. et al. Ospedale Maggiore S. Giovanni Battista, Torino, Italy. Minerva Med. 77: 19-25, 1986.

The usefulness of assaying tumoral mar- kers in lung cancer is examined. 63 patients (56 men and 7 women) suffering from various types of malignant lung cancer were examined and compared with 44 patients hsopitalised for benign lung complaints. The markers used were CEA, Ferritin, GICA and TPA. Ferritin proved the most sensitive marker with 73% positive results for tumours as opposed to 47.6% for CEA and GICA and only 19% for TPA. The division of tumours into histological types (adenocarcinomas, squamous cell carci- nomas, microcytomas and large cell anapla- stic carcinomas) showed that Ferritin is the best marker for lung cancer (70% posi- tive results in adenocarcinomas and squa- mous cell carcinomas, 62.5% in microcytomas,

87.5% in large cell anaplastic carcinomas).

~Aand GICA display almost the same level of sensitivity in the different histological types: the sensitivity of TPA is low in all cases. Specificity was found to be satis- factory for all markers examined. It may be concluded that best results are obtained by combining the Ferritin assay with CEA and/or GICA tests.

Evaluation of a Radioinmunoassay for Neuron Specific Enolase in Small Cell Lung Cancer. cooper, E.H., Splinter, T.A.W., Brown, D.A. et al. Unit for Cancer Research, University of Leeds, Leeds LS2 9JT, U.K. Br. J. Cancer 52: 333-338, 1985.

A radioimmunoassay for neuron specific enolase (NSE), a marker of neuroendocrine differentiation, has been evaluated in small cell lung cancer (SCLC). In untreated patients 25/38 (68%) with localized SCLC had raised blood levels of NSE (>13 ng/ml ), in exten- sive disease 34/39 (87%) patients had raised NSE levels. In patients with non-small cell lung cancer (NSCLC) the serum levels were raised in 16/94 (17%). In extensive tumours of non-pulmonary origin NSE levels were increased in 24/116 (20%) patients. Longitu- dinal studies indicated a good correlation between the response to chemotherapy and fall of NSE levels. Tumour progression was accom- panied by a rising NSE in 25/29 patients~ with doubling times of 7-90 days. In patients with progression with a normal NSE the recur- rence was a NSCLC. Cerebral metastases oc- curring.as the only recurrence during clinical complete remission were not accompanied by a rise of NSE. Serum NSE levels provides a va- luable monitor for SCLC during and after chemo- therapy.

Creatine Kinase B Subunit as a Biomarker for Small Cell Carcinoma of the Lung: Comparison with Ganmm-enolase. Kato, K., Ariyoshi, Y., Nakajima, T. Depart- ment of Biochemistry, Institute for Develop- ment Research, Aichi Prefectural Colony, Aichi 480-03, Japan. Jpn. J. Cancer Res., Gann 76: 1162-1167, 1985.

Concentrations of creatine kinase (CK) B subunit (CK-B) in tumor tissues and in sera of patients with various lung carcinomas were determined, together with the concen- trations of neuron-specific gamma-enolase (gamma subunit of alphagamma and gammagamma enolases), by theuse of a sensitive enzyme immunoassay method. The CK-B and gamma-eno- lase levels were enhanced in tissues of small cell carcinoma of the lung. The average tis- sue contents of CK-B in small cell carcinoma (SCCL), adenocarcinoma (ADCL) and squamous cell carcinoma (ECCL) of the lung, and nor- mal lung were 2320, 308, 163, and 372 ng/mg protein, respectively. The contents of gamma- enolase in those tissues were 1460, 276, 225, and 42.7 ng/mg protein, respectively. Serum

Page 2: Creatine kinase B subunit as a biomarker for small cell carcinoma of the lung: Comparison with gamma-enolase

CK-B concentrations in healthy adults (n = i00) were 0.53 + or - 0.22 ng/ml and ranged from 0.25 to 1.44 ng/ml, but they were sig- nificantly increased (> 1.5 ng/ml) in some patients with SCCL (26/42 cases, 62%), ADCL (7/36, 19%), ECCL (7/37, 19%), and large cell carcinoma of the lung (LCCL, 4/13, 31%). Serum CK-B was also enhanced in some patients with breast carcinoma and in a few cases in carcinomas of the stomach, colon and pancreas. Serum concentrations of CK-B were well correlated with those of gamma-enolase in patients with SCCL (r= 0.667, n=83, P<0.01) and LCCL (r=0.689, n=20, P<0.01), but poorly in patients with ADCL and ECCL. Since serum CK-B concentra- tions in patients with SCCL changed in pa- rallel with the clinical course during treatment, serum CK-B may also be a useful biomarker, as well as neuron-specific gam- ma-enolase, for monitoring the clinical course of patients with SCCL.

Cerebrospinal Fluid ACTH as a Marker of Central Nervous System Metastases from Small Cell Carcinoma of the Lung. Pedersen, A.G., Hamsen, M., Hummer, L., Rogowski, P. Department of Chemotherapy, The Finsen Institute, DK-2100 Copenhagen, Denmark. Cancer 56: 2456-2480, 1985.

Adrenocorticotrophic hormone (ACTH) concentrations were measured in the plasma and cerebrospinal fluid (CSF) of 107 conse- cutive patients with known or suspected central nervous system (CNS) metastases se- condary to small cell carcinoma of the lung. The combined results of computerized tomo- graphy scans, neurologic examination, and autopsy were used to determine the presence or absence of CNS metastases. On the basis of such an assessment, definitive conclu- sions were possible in 77 patients. CNS metastases were present in 52 cases and absent in 25. The median CSF ACTH level was 30 ng/ml in both groups. None of 5 pa- tients with very high CSF ACTH concentra- tions had elevated ACTH concentrations in plasma. Considering the 95th percentile of patients without CNS metastases as the upper limit of normal, 12 patients with metastases and 1 without had an elevated CSF ACTH value. Eleven patients with lep- tomeningeal carcinomatosis (MC) did not constitute a special subgroup in this re- spect. The median ratio of CSF ACTH and plasma ACTH was 1.0 in patients with CNS metastases and 0.4 in those without (P< 0.05). Ten patients with CNS metastases (i with MC) and 1 without exceeded the upper 95th percentile of the CSF/plasma (ACTH) ratio in patients without CNS meta- stases. The significance levels of these findings disappeared, however, when patients with signs of an elevated ACTH concentra-

tion in plasma were excluded. Patients

265

with ectopic ACTH production into CSF do

not necessarily have ectopic ACTH produc- tion outside the CNS, despite the presence of extracerebral metastases. With the cri- teria employed in this study, an elevated level of CSF ACTH diagnosed too few patients for the authors to recommend its determina- tion as a single test in diagnosing CNS me- tastases or MC secondary to small cell car- cinoma of the lung.

Prognostic Value of Serum and Tissue CEA in Lung Cancer. Leonardo, E., Navone, R., Dogliotti, C., Oliaro, A. Universita di Torino, Instituto di Anatomia e Istologia Patologica, Catte- dra di Tecnica e Diagnostica Citopatologica, Torino, Italy. Minerva. Med. 76: 2111-211~, 1985.

Serum concentration of carcinoembryonic antigen (CEA) was determined in 53 lung cancer patients before and 1 month after surgery. Relationships between serum CEA levels after and before surgery and survi- val were demonstrated. Furthermore, histo- logical sections of the neoplastic surgical material were stained with anti human CEA antibody using an immunohistochemical method. The positivity of the neoplastic cells and of the macrophages was then analyzed and discussed.

The Role of Serum T~our Markers to Aid the Selection of Lung Cancer Patients for Sur- gery and the Assessment of Prognosis. Muller, T., Marshall, R.J., Cooper, E.H. et al. Unit for Cancer Research, Leeds Univer- sity, Leeds LS2 9NL, U.K. Eur. J. Cancer Clin. Oncol. 21: 1461-1466, 1985.

We have measured the following ten serum proteins in a sample of 290 patients pre- senting with possible lung cancer: carcino- embryonic antigen (CEA), alpha.-acid gly-

1 coprotein (AGP), C-reactive protein (CRP), ferritin (FER), prealbumin (PAB), third component of complement (C3), immunoglobin E (IgE), alpha2-pregnancy-associated gly- coprotein (PAGI, beta2microglobulin (beta2-m) and retinol binding protein (RBP). It is found that, with the exception of PAG, C3 and IgE, there are significant differences between protein concentrations in the sub- sequently diagnosed cancer and non-cancer patients. However, protein concentrations in the cancer patients who were suitable for surgery do not differ significantly from the concentrations in inoperable pa- tients. The prognostic significance of the proteins in the inoperable and operable cancer patients is also envisaged. In the operable group C3 appears to be useful, whilst AGP and RBP are prognostic indicators in the inoperable group.

Serum Copper and Zinc Levels in Lung Cancer Patients.