CLB-08852; No. of pages: 5; 4C: Clinical Biochemistry xxx (2014) xxx–xxx

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Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers M. Patout a,⁎, M. Salaün a, V. Brunel b, S. Bota a, B. Cauliez b, L. Thiberville a a b

Clinique Pneumologique, Hôpital Charles Nicolle, CHU de Rouen, 1 rue de Germont, 76031 Rouen Cedex, France Institut de Biologie Clinique, Hôpital Charles Nicolle, CHU de Rouen, 1 rue de Germont, 76031 Rouen Cedex, France

a r t i c l e

i n f o

Article history: Received 25 May 2014 Received in revised form 30 August 2014 Accepted 2 September 2014 Available online xxxx Keywords: Small-cell lung cancer Liver metastasis Procalcitonin Prognostic factor Non-small-cell lung cancer

a b s t r a c t Objectives: Procalcitonin (PCT) is widely used for the diagnosis of bacterial infections. The aim of this study was to evaluate PCT as a tumor and as a prognostic marker in patients with primary lung cancer. Design and methods: We retrospectively performed a PCT dosage in the frozen serum samples of 147 patients with pulmonary neoplasia for whom a test of neuron-specific enolase (NSE) had been conducted at the time of diagnosis. Results: We show that a PCT serum level above 0.15 ng/mL was independently linked to the presence of a neuroendocrine component in the tumor (HR = 5.809 95% CI [1.695–19.908] p: 0005). Thus, median PCT serum levels were significantly more elevated in small-cell lung cancers than in pulmonary adenocarcinomas: 0.33 ng/mL versus 0.07 ng/mL (p b 0.001). However, the diagnostic value of serum PCT levels for diagnosing carcinoma with a neuroendocrine component remains low (sensitivity 63.8%; specificity 71.9%). In this series, serum PCT levels were significantly more elevated in the presence of liver metastases: 0.37 ng/mL versus 0.09 ng/mL in the absence of liver metastasis (p b 0.001). In uni- and multivariate analyses, a serum PCT level above 0.15 ng/mL and the presence of metastases and of sepsis at the time of diagnosis were independent factors of unfavorable prognosis. Conclusions: Serum PCT is elevated in patients with lung cancer with neuroendocrine component or with liver metastases. As a consequence, in this population, PCT has a poor specificity for bacterial infection. At diagnosis, an elevated serum PCT is an independent predictive factor of bad prognosis. © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Introduction Serum procalcitonin (PCT) is a biomarker for the early diagnosis of bacterial infections. PCT, the precursor of calcitonin, is a protein composed of 116 amino acids encoded by the CALC gene. PCT is mainly synthesized by the thyroid gland. Extrathyroidal synthesis of PCT has been reported, particularly pulmonary and hepatic synthesis [1]. Testing serum levels of PCT is used to diagnose bacterial infections in their initial phase, due to its greater specificity and earlier elevation compared with C-reactive protein (CRP) with a sensitivity of 60% and a specificity of 100% in patients with febrile neutropenia [2]. Its use as a marker for infection has been validated in numerous clinical situations, including cancer patients [3–6]. PCT is also employed to adapt the usage strategy of antibiotics in intensive care patients [7,8]. PCT has been identified as a prognostic marker for sepsis [7].

⁎ Corresponding author at: Hôpital Charles Nicolle, Rouen University Hospital, 1 rue de Germont, 76031 Rouen, France. Fax: +33 2 32 88 82 40. E-mail address: [email protected] (M. Patout).

PCT can, however, be elevated when there is no infectious process, in particular in tumorous diseases like medullary thyroid cancer, in which PCT is secreted by the tumor cells. Elevated PCT is associated with shorter survival in medullary thyroid cancer [8]. PCT is also elevated in the presence of liver metastases regardless of the primary neoplasm [9]. Lung cancer is the most common cause of cancer-related death in Europe [10]. Tumors with neuroendocrine differentiation represent 15–20% of all lung cancers [11]. Neuroendocrine lung cancers are known to express neuroendocrine markers such as Chromogranin A, Synaptophysin and Neuron Specific Enolase (NSE). Among these potential tumor markers, NSE is the most used as a serum tumor marker with a sensitivity of 72% and a specificity of 94% for the diagnostic of small cell lung carcinoma [12]. In 1980, it was shown that bronchial cancer could be accompanied by an increase in serum calcitonin concentrations [13, 14]. In these studies, however, the assay techniques used could not distinguish calcitonin from PCT. Later, it has been shown that small-cell lung cancer cell lines could produce PCT in vitro [15]. To our knowledge, no data is available on the PCT secretion levels in patients with neuroendocrine bronchopulmonary neoplasia.

http://dx.doi.org/10.1016/j.clinbiochem.2014.09.002 0009-9120/© 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Please cite this article as: Patout M, et al, Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers, Clin Biochem (2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.09.002

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M. Patout et al. / Clinical Biochemistry xxx (2014) xxx–xxx

Methods All the serum samples from patients who underwent a NSE test in the University Hospital of Rouen, France, between December 2008 and November 2010 were preserved. The serum samples from patients who had histologically confirmed bronchopulmonary neoplasia and whose test had been conducted before any treatment was initiated were selected. A total of 466 serum NSE samples were available; we excluded 158 (34%) sera from patients with extrapulmonary primary cancers, 100 (22%) sera from patients without cancer and 58 (12%) sera taken from patients with lung cancers treatment initiation. Of the 149 (32%) sera from patients with histologically proven lung cancer sampled before treatment, 2 (1%) were excluded because of insufficiency of sera left in the sample. Finally, 147 (31%) sera samples were included in the study (Fig. 1). Patients Aside from NSE serum levels, patients' clinical data (age and gender), anatomical–pathological data, and data from their initial assessment of tumor extent were collected from the computerized archives of Rouen University Hospital. At enrollment, a note was made regarding the presence of sepsis, defined as febrile illness combined with leukocytosis requiring an antibiotic treatment to be initiated. The data relating to survival was calculated on February 28, 2011. Median follow-up was 162 days (63–292). At the time of analysis, 88 (60%) patients were deceased. Median age was 63 (56–71). Men accounted for 73% of the patients. Fifty-seven (39%) patients exhibited a tumor with a neuroendocrine component. Sixty-seven (46%) patients had lung adenocarcinomas cancer, 51 (35%) had small cell lung cancer, 21 (14%) had squamous-cell lung cancer, 6 (4%) had large cell cancers with neuroendocrine contingent and 2 (1%) had sarcomas. Metastatic patients numbered 103 (71%): 47 (46%) had liver metastasis, 38 (37%) had bone metastasis, 33 (32%) had cerebral metastasis, 32 (31%) had adrenal metastasis, 24 (23%) had pleural metastasis and 24 (23%) had contralateral lung metastasis.

Fig. 1. Sample flowchart.

In this study, we tested the hypothesis that the serum PCT concentrations could be elevated in bronchial cancer without any bacterial infection. We also assessed its diagnostic and prognostic value as a tumor marker compared with NSE. The preliminary results of this study have been reported at the annual meeting of the American Society of Clinical Oncology and at the European Respiratory Society in 2011.

Biological tests The PCT and CRP biological tests were conducted on the patients' frozen serum samples that had been used for the initial NSE test. Serum NSE was assessed using the immunometric assay (Immulite

Table 1 Predictors of increased PCT levels above 0.15 ng/mL in univariate and multivariate analyses.

Age Sex Sepsis Neuroendocrine component Lymph node status Metastasis status C-reactive protein Neuronspecific enolase

Under 65 years old Over 65 years old Female Male No Yes No Yes N0 N1/2/3 No Yes Inferior to 10 mg/L Superior to 10 mg/L Inferior to 16 μg/L Superior to 16 μg/L

Patients with PCT level above 0.15 ng/mL

Univariate analysis

n (% of all study population)

OR [CI 95%]

38 (63) 26 (30) 10 (26) 54 (50) 47 (41) 9 (81) 26 (30) 38 (67) 6 (32) 58 (45) 13 (30) 51 (50) 9 (28) 55 (48) 22 (27) 42 (65)

1 0.2 [0.06–0.6] 1 2.9 [1.3–6.5] 1 6.6 [1.4–31.9] 1 4.6 [2.3–9.4] 1 1.8 [0.6–5] 1 2.45 [1.1–5.3] 1 2.3 [1–5.5] 1 4.9 [2.5–10.1]

Multivariate analysis p 0.006 0.01 0.019 b0.001 0.265 0.023 0.05 b0.001

OR [CI 95%]

p

1 0.46 [0.1–1.9] 1 1.8 [0.6–5.3] 1 5.6 [1–31.6] 1 5.1 [1.3–20.2] 1 0.4 [0.06–2.6] 1 6.01 [1.7–21.7] 1 3.11 [0.99–9.8] 1 2.06 [0.6–6.9]

0.282 0.296 0.05 0.02 0.329 0.006 0.053 0.244

Please cite this article as: Patout M, et al, Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers, Clin Biochem (2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.09.002

M. Patout et al. / Clinical Biochemistry xxx (2014) xxx–xxx

2000, DPC, USA). PCT and CRP tests were conducted in a blinded manner with regard to the histological diagnosis, the assessment of tumor extent, and all other demographical and clinical data. The serum samples chosen were kept at a temperature of − 20 °C. The PCT test was conducted with the KRYPTOR automated system (B.R.A.H.M.S, Germany) using TRACE technology based on immunoluminometric assay, which use two monoclonal antibodies specific to two residues of PCT. The test required 50 μL of serum and has a sensitivity to detect a change of 0.06 ng/mL of PCT with a probability of 95%. The CRP test was conducted by nephelometry with the automated analyzer BN II (SIEMENS, Germany). The test required 40 μL of serum. Statistical analysis

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and 0.37 ng/mL (0.10–1.37) in its presence. This difference was not found for the other tumor locations (Table 2). Similarly, NSE was elevated in the presence of hepatic metastases regardless of the histological type, the median going from 63 (14–309) in their presence to 11.24 (8.1–25.4) in their absence. Overall, 64 (44%) tests were above the 0.15 ng/mL threshold value and 33 (22%) tests were above the threshold of 0.5 ng/mL, the value used for diagnosing systemic bacterial infection. Of these 33 patients, 25 did not display any signs of bacterial infection at the time of sampling. Calculated sensitivity of the PCT assay for the diagnostic of bacterial infection was: 36%, 50% and 67% for the entire group of patients, the neuroendocrine tumor group and liver metastasis group, respectively. Calculated specificity of the PCT assay for the diagnostic of bacterial infection was: 78, 62% and 59% for the entire group of patients, the neuroendocrine tumor group and liver metastasis group, respectively.

Comparisons were made using Chi-squared, Mann–Whitney and Kruskal–Wallis tests when appropriate. Survival data were analyzed using the Kaplan–Meier method and Log-rank test. The association between the various parameters and survival was analyzed by means of a Cox model with a 95% confidence interval and forward selection with an entry threshold of 5% and a deletion threshold of 10%. The diagnostic value of PCT was assessed by means of ROC curves. All tests were two-tailed with a threshold of 5%. The analyses were performed by means of PASW Statistics v.19® (IBM, USA) and Excel 2011, Mac Edition® (Microsoft, Seattle, USA). Results Of the 466 serum samples available, 147 were included in the study (Fig. 1). The median concentration of PCT was 0.12 ng/mL (0.063–0.416), that of CRP was 32 mg/L (11–82), and that of NSE was 13.7 μg/L (9–41). In univariate analysis, PCT was significantly more elevated in men (p: 0.0089), in patients aged under 65 years (p: 0.004), in those with sepsis (p: 0.031), as well as in those with neuroendocrine neoplasia (p b 0.001) or metastases (p: 0.025). PCT was significantly more elevated in patients who displayed a concentration of CRP above 10 mg/L (p b 0.012) and of NSE above 16 μg/L (p b 0.001). In multivariate analyses, the neuroendocrine nature of the tumor (HR = 5.8; 95% CI [1.7–19.9] p: 0005), the presence of sepsis upon the PCT test (HR = 7.1; 95% CI [1.3–40.4]; p: 0.026), and the presence of metastases (HR = 3.8; CI 95% [1.3–10.7]; p: 0.012) were factors that were independently associated with a PCT concentration above 0.15 ng/mL (Table 1). Median serum concentrations of PCT varied significantly depending on histological type (p b 0.001). Median PCT concentration was 6.79 ng/mL (0.057–14.58) for large-cell carcinoma with a neuroendocrine component; 0.33 ng/mL (0.11–0.99) for small-cell carcinoma; 0.11 ng/mL (0.06–0.16) for large-cell carcinoma; 0.1 ng/mL (0.05–0.18) for squamous carcinoma; and 0.07 ng/mL (0.05–0.14) for adenocarcinoma. Regardless of histological type, PCT levels were significantly more elevated if there was hepatic metastasis, with a median concentration of 0.09 ng/mL (0.051–0.18) in the absence of hepatic metastasis

Table 2 Serum procalcitonin levels depending on metastasis sites. Metastasis site

Absent median 1st–3rd quartile

Present median 1st–3rd quartile

P

Liver Bone Adrenal gland Lung Pleura Brain

0.09 (0.051–0.18) 0.108 (0.061–0.333) 0.108 (0.058–0.416) 0.111 (0.062–0.376) 0.108 (0.061–0.416) 0.107 (0.062–0.373)

0.37 (0.1–1.37) 0.207 (0.065–0.946) 0.147 (0.081–0.474) 0.137 (0.061–1.169) 0.123 (0.093–0.466) 0.159 (0.059–0.466)

b0.001 0.155 0.175 0.572 0.586 0.65

Fig. 2. ROC curves of PCT and NSE for the diagnosis of neuroendocrine tumors (Panel A) and of hepatic metastases (Panel B).

Please cite this article as: Patout M, et al, Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers, Clin Biochem (2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.09.002

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M. Patout et al. / Clinical Biochemistry xxx (2014) xxx–xxx

Fig. 3. Kaplan–Meier overall survival curves of patients with primary lung cancers according to serum PCT levels at the time of diagnosis (Log-rank test, p b 0.001).

Diagnostic value of PCT for the diagnostic of neuroendocrine tumors has been calculated at the threshold of 0.15 ng/mL. Fig. 2 shows the ROC curves of PCT and NSE for diagnosing neuroendocrine tumors. The sensitivity of PCT was 63.8% and its specificity was 71.9% for detecting the existence of a neuroendocrine component in the tumor (small-cell carcinoma and large-cell neuroendocrine carcinoma). The NSE test performed better for the same indication than the PCT test. PCT's sensitivity was 66% and its specificity was 69.4% for diagnosing liver metastases all histological classifications taken together (Fig. 2). NSE performed similarly for the diagnosis of hepatic metastases. Fig. 3 shows the survival curves, regardless of the histological type, according to the serum concentration of PCT at a threshold of 0.15 ng/mL. Median length of survival was 156 days for all the patients taken together. The length of survival was significantly shorter in the group whose PCT was above 0.15 ng/mL at diagnosis than it was in the group whose PCT was below 0.15 ng/mL (median survival = 91; 95% CI [53–129] vs. 353; 95% CI [238–468]; p b 0.001).

In univariate analysis, the level of PCT and the presence of sepsis or metastases at diagnosis were factors that were significantly associated with survival (Table 3). However, analysis of the causes of death showed that no death occurred because of sepsis in the days following the taking of the serum sample on which the PCT test was conducted. In multivariate analyses, the independent factors that were significantly associated with shorter survival were a PCT value above 0.15 ng/mL (HR = 1.67; 95% CI [1.05–2.22]; p: 0.029); the presence of sepsis at the time of the PCT test (HR = 3.49; 95% CI [1.72–7.07]; p: 0.001); and the presence of metastases (HR = 2.072; 95% CI [1.19–3.62]; p: 0.01). Discussion This study shows that PCT levels are elevated in the presence of tumors with a neuroendocrine component or of liver metastases of lung cancer. This results in a lower specificity of the PCT assay for the

Table 3 Predictors of mortality in univariate analysis.

Gender Sepsis at dosage Histology Lymph node status Metastasis status Age Procalcitonin C-reactive protein Neuronspecific enolase

Female (n: 39) Male (n: 108) No (n: 116) Yes (n: 11) Absence of neuroendocrine contingent (n: 57) Presence of neuroendocrine contingent (n: 89) N0 (n: 18) N1/2/3 (n: 128) Absence of metastases (n: 42) Presence of metastases (n: 105) Under 65 years old Over 65 years old Inferior to 0.15 ng/mL Superior to 0.15 ng/mL Inferior to 10 mg/L Superior to 10 mg/L Inferior to 16 μg/L Superior to 16 μg/L

Median survival (95% CI)

HR (95% CI)

279 (150–408) 212 (50–374) 247 (117–377) 23 (0–62) 146 (65–321) 156 (56–284) 349 (85–611) 212 (110–315) 348 (219–477) 125 (1–249) 183 (85–293) 117 (34–296) 210 (101–351) 89 (28–255) 214 (91.5–343) 124 (45–282) 125 (37–285) 164 (79–314)

1 0.916 (0.575–1.46) 1 3.429 (1.745–6.741) 1 1.048 (0.679–1.618) 1 1.6 (0.8–3.197) 1 1.784 (1.068–2.980) 1 1.519 (0.989–2.333) 1 2.248 (1.466–3.446) 1 1.8 (0.997–3.249) 1 1.136 (0.742–1.74)

p (log-rank test) 0.713 b0.001 0.834 0.182 0.027 0.056 b0.001 0.051 0.557

Please cite this article as: Patout M, et al, Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers, Clin Biochem (2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.09.002

M. Patout et al. / Clinical Biochemistry xxx (2014) xxx–xxx

diagnostic of bacterial infection in this group of patients compared to published values in non cancerous patients. Our findings also show that elevated PCT levels constitute a negative predictive factor of survival that is independent of the presence of sepsis and of metastases. Apart from revealing the secretion of PCT in tumor cell lines of smallcell carcinoma [15], no publication has evaluated PCT values in cancer with a neuroendocrine component till now. In our study, we showed that such an elevation was present in small-cell carcinomas, as well as in large-cell carcinomas with a neuroendocrine component. These results shed new light on previous data regarding calcitonin tests in bronchopulmonary neoplasia [13,14]. They offer new arguments in favor of the existence of PCT synthesis by neuroendocrine cells [16]. Aside from cancers with a neuroendocrine component, elevated PCT levels in patients with hepatic metastases are in line with a previous study that demonstrated significantly higher serum PCT levels in patients who displayed liver metastases compared with healthy subjects and patients without metastases [9]. The increase in serum PCT levels in patients with liver metastases may be linked to the production of PCT by hepatocytes in response to peritumoral inflammation [17], regardless of the tumor's histological type. Owing to its low sensitivity, which is inferior to that of NSE, PCT cannot be considered a useful tumor marker for diagnosing carcinomas with a neuroendocrine component, in particular small-cell carcinomas. PCT at the time of diagnosis is, however, an independent prognostic factor for the extent of the tumor and the presence of sepsis. This data is consistent with that established for medullary thyroid cancers [8]. Our survival results may be accounted for by a greater PCT elevation in the most aggressive tumors, which are associated with a nonspecific inflammatory response secondary to the neoplasia [18–20], as was shown for CRP. On the other hand, the PCT specificity of 62 and 59% for bacterial infection in patients who display bronchial neoplasia with a neuroendocrine component or with liver metastases should lead clinicians to use and interpret PCT results prudently. For instance, using PCT to distinguish a fever related to tumor progression from a fever caused by a bacterial infection does not appear relevant as its elevation may be due to either etiology. The main methodological criticism of our study is that the tests were conducted several months after the samples were taken. However, Meisner et al. [21] showed that PCT was a stable protein that could be assayed at a later time and after freezing. Another potential bias in the study is linked to the selection of the patients based on previous serum NSE analysis, which has selected more patients with small cell histology, and patients with advanced lung cancers; therefore, the conclusions of the present study may not be applicable to early stage non small cell lung cancers, a situation where PCT may remain valuable for the diagnostic of bacterial infection. Further studies are needed to assess the value of PCT in this situation. Conclusion These study results should lead physicians to prudently interpret PCT tests for diagnosing bacterial infection in patients who display lung cancers with a neuroendocrine component or who exhibit a primary lung cancer with liver metastases, regardless of their histology. A PCT above 0.15 ng/mL at diagnosis is an independent factor of bad prognosis in bronchopulmonary tumors but, unlike the case of thyroid tumors, it cannot be used as a useful diagnostic tumor marker.

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Funding This work was supported by the Groupe Rouennais d'Etudes Pneumologiques (Rouen pulmonology study group), Rouen, France which provided fundings for the PCT test kits. Disclosure The authors have declared no conflicts of interest. References [1] Russwurm S, Stonans I, Stonane E, Wiederhold M, Luber A, Zipfel PF, et al. Procalcitonin and CGRP-1 mrna expression in various human tissues. Shock 2001; 16:109–12. [2] Bernard L, Ferrière F, Casassus P, Malas F, Lévêque S, Guillevin L, et al. Procalcitonin as an early marker of bacterial infection in severely neutropenic febrile adults. Clin Infect Dis 1998;27:914–5. [3] Feld R. Bloodstream infections in cancer patients with febrile neutropenia. Int J Antimicrob Agents 2008;32(Suppl. 1):S30–3. [4] Prat C, Sancho JM, Dominguez J, Xicoy B, Gimenez M, Ferra C, et al. Evaluation of procalcitonin, neopterin, C-reactive protein, IL-6 and IL-8 as a diagnostic marker of infection in patients with febrile neutropenia. Leuk Lymphoma 2008;49: 1752–61. [5] Sandri MT, Passerini R, Leon ME, Peccatori FA, Zorzino L, Salvatici M, et al. Procalcitonin as a useful marker of infection in hemato-oncological patients with fever. Anticancer Res 2008;28:3061–5. [6] Fleischhack G, Kambeck I, Cipic D, Hasan C, Bode U. Procalcitonin in paediatric cancer patients: its diagnostic relevance is superior to that of C-reactive protein, interleukin 6, interleukin 8, soluble interleukin 2 receptor and soluble tumour necrosis factor receptor II. Br J Haematol 2000;111:1093–102. [7] Heper Y, Akalin EH, Mistik R, Akgöz S, Töre O, Göral G, et al. Evaluation of serum Creactive protein, procalcitonin, tumor necrosis factor alpha, and interleukin-10 levels as diagnostic and prognostic parameters in patients with communityacquired sepsis, severe sepsis, and septic shock. Eur J Clin Microbiol Infect Dis 2006;25:481–91. [8] Walter MA, Meier C, Radimerski T, Iten F, Kränzlin M, Müller-Brand J, et al. Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer. Cancer 2010;116:31–40. [9] Matzaraki V, Alexandraki KI, Venetsanou K, Piperi C, Myrianthefs P, Malamos N, et al. Evaluation of serum procalcitonin and interleukin-6 levels as markers of liver metastasis. Clin Biochem 2007;40:336–42. [10] Malvezzi M, Arfé A, Bertuccio P, Levi F, La Vecchia C, Negri E. European cancer mortality predictions for the year 2011. Ann Oncol 2011;22:947–56. [11] Lortet-Tieulent J, Soerjomataram I, Ferlay J, Rutherford M, Weiderpass E, Bray F. International trends in lung cancer incidence by histological subtype: adenocarcinoma stabilizing in men but still increasing in women. Lung Cancer 2014;84: 13–22. [12] Burghuber OC, Worofka B, Schernthaner G, Vetter N, Neumann M, Dudczak R, et al. Serum neuron-specific enolase is a useful tumor marker for small cell lung cancer. Cancer 1990;65:1386–90. [13] Silva OL, Becker KL, Primack A, Doppman JL, Snider RH. Increased serum calcitonin levels in bronchogenic cancer. Chest 1976;69:495–9. [14] Becker KL, Nash DR, Silva OL, Snider RH, Moore CF. Urine calcitonin levels in patients with bronchogenic carcinoma. JAMA 1980;243:670–2. [15] Cate CC, Pettengill OS, Sorenson GD. Biosynthesis of procalcitonin in small cell carcinoma of the lung. Cancer Res 1986;46:812–8. [16] Becker KL, O'Neil WJ, Snider RH, Nylen ES, Moore CF, Jeng J, et al. Hypercalcitonemia in inhalation burn injury: a response of the pulmonary neuroendocrine cell? Anat Rec 1993;236:136–8 [172–3; discussion138–43]. [17] Vermeulen PB, Colpaert C, Salgado R, Royers R, Hellemans H, Van Den Heuvel E, et al. Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia. J Pathol 2001;195:336–42. [18] Monneret G, Pachot A, Laroche B, Picollet J, Bienvenu J. Procalcitonin and calcitonin gene-related peptide decrease LPS-induced tnf production by human circulating blood cells. Cytokine 2000;12:762–4. [19] Whang KT, Vath SD, Becker KL, Snider RH, Nylen ES, Muller B, et al. Procalcitonin and proinflammatory cytokine in interactions in sepsis. Shock 1999;12:268–73. [20] Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860–7. [21] Meisner M, Tschaikowsky K, Schnabel S, Schmidt J, Katalinic A, Schüttler J. Procalcitonin—influence of temperature, storage, anticoagulation and arterial or venous asservation of blood samples on procalcitonin concentrations. Eur J Clin Chem Clin Biochem 1997;35:597–601.

Please cite this article as: Patout M, et al, Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers, Clin Biochem (2014), http://dx.doi.org/10.1016/j.clinbiochem.2014.09.002

Diagnostic and prognostic value of serum procalcitonin concentrations in primary lung cancers.

Procalcitonin (PCT) is widely used for the diagnosis of bacterial infections. The aim of this study was to evaluate PCT as a tumor and as a prognostic...
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