|Year : 2016 | Volume
| Issue : 1 | Page : 355-358
Diagnostic value of bronchoalveolar lavage fluid and serum tumor markers for lung cancer
Hongmin Wang1, Xiaohong Zhang2, Xinkui Liu3, Kangdong Liu4, Yuexia Li1, Haijiang Xu1
1 Department of Respiratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
2 Department of Respiratory, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China
3 Department of Medical Records Management, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4 Department School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
|Date of Web Publication||13-Apr-2016|
Department of Respiratory, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou - 450 052
Source of Support: None, Conflict of Interest: None
Objective: To analyze the changes of bronchoalveolar lavage fluid (BALF) and serum tumor markers in lung cancer.
Materials and Methods: Fifty patients with lung cancer (study group) and 50 cases with benign lung lesions (control group) were selected from May, 2010 to May, 2013. The observation group included squamous cell carcinoma subgroup (n = 25), adenocarcinoma subgroup (n = 19), and small cell undifferentiated carcinoma subgroup (n = 6). The carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment (CYFRA21-1) concentration were compared; and the comparisons among subgroups were also performed.
Results: Three kinds of tumor markers in BALF and serum of the observation group were higher than that of the control group. NSE concentration of small.cell lung cancer was the highest, CYFRA21.1 concentration was highest in the squamous cell carcinoma, and CEA concentration was highest in the adenocarcinoma group; the former increased more significantly.
Conclusion: BALF and serum NSE, CEA, and CYFRA21.1 elevated in lung cancer, which had prompt value for pathology, especially significant for BALF.
Keywords: Bronchoalveolar lavage fluid, lung cancer, serum tumor markers
|How to cite this article:|
Wang H, Zhang X, Liu X, Liu K, Li Y, Xu H. Diagnostic value of bronchoalveolar lavage fluid and serum tumor markers for lung cancer. J Can Res Ther 2016;12:355-8
|How to cite this URL:|
Wang H, Zhang X, Liu X, Liu K, Li Y, Xu H. Diagnostic value of bronchoalveolar lavage fluid and serum tumor markers for lung cancer. J Can Res Ther [serial online] 2016 [cited 2019 Nov 12];12:355-8. Available from: http://www.cancerjournal.net/text.asp?2016/12/1/355/162111
| > Introduction|| |
Lung cancer was one of common clinical malignant tumor. The latest survey showed that the incidence of cancer in men ranked first, and third in women. As one of the important diagnostic aid in early diagnosis of lung cancer, lung tumor markers included carcinoembryoinc antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1), CK19-2G2, and others. NSE showed a promising predictive value of SCEC, the concentration of which also predicted the sensitivity of therapy effectiveness. High serum levels of CEA and/or CYFRA 21-1 were associated with poor outcome of patients with non-small cell undifferentiated carcinoma (NSCLC). Besides advanced lung cancer, CYFRA21-1 also had remarkable prognostic significance for epithelial ovarian cancers.
Currently, more researches about lung cancer tumor markers were serum-based., The number of studies taking bronchoalveolar lavage fluid (BALF) for markers still needed to be increased, which represented a promising noninvasive source of lung cancer-specific protein biomarkers with high diagnostic accuracy. Although infiltration of inflammatory cells and production of pro-angiogenic factors were important in lung cancer immunity, the higher levels of interleukin (IL)-8 and vascular endothelial growth factor (VEGF) contributed to the lung cancer. Changes of the cytokines in BALF reflected immunologic reactions of the lung in pulmonary malignancies, such as transforming growth factor (TGF)-β1, but TGF-α and IL-6 has poor diagnostic value for lung cancer.
In this study, 100 hospitalized patients admitted to thoracic medicine department of our hospital from May, 2010 to May 2013 were randomly selected and divided into observation group (patients diagnosed with lung cancer) and control group (benign lung disease). Electric chemiluminescence method and enzyme-linked immunosorbent assay were performed. The BALF and serum CEA, NSE, and CYFRA21-1 concentration of the two groups were collected, and the results were compared to preliminarily understand the BALF and serum tumor markers in the diagnosis of lung cancer, and the lung cancers of the patients were divided into small cell lung cancer, squamous cell carcinoma, and adenocarcinoma in accordance with the pathological findings. The concentration differences of these tumor markers in three different pathological features of lung cancer were observed to aim at improving the ability of lung cancer diagnosis. The detailed report was as follows.
| > Materials and Methods|| |
The subjects were 100 hospitalized patients randomly selected from thoracic medicine department of our hospital from May, 2010 to May, 2013, and divided into observation and control group. The 50 cases in the observation group were diagnosed to be lung cancer by histology, cytology, and other techniques, including 29 male and 21 female cases, aged 35–81 years with mean age of 55.7 ± 4.9 years. The observation group included 25 cases with squamous cell carcinoma, 19 cases with adenocarcinoma, and six cases with NSCLC. The 50 cases in the control group were diagnosed to be benign lung disease by bacterial culture, imaging, and pathology; including 27 male cases and 23 female cases, aged 36–82 years with mean age 56.3 ± 5.1 years. The control group included 21 cases with pneumonia, eight cases with tuberculosis, six cases with lung abscess, five cases with bronchiectasis, four cases with chronic bronchitis, and six cases with lung fibrosis. There were no significant differences in patient aspects such as gender and age, which was comparable, P > 0.05 [Table 1]. This study was conducted in accordance with the Declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Zhengzhou University. Written informed consent was obtained from all the participants.
Tumor marker acquisition
The patients in the observation and the control group both underwent bronchoscopy routine operation. The tumor and other lesion sites of the cancer patients were selected as bronchial openings, the fiber bronchi were wedged in. The diffused lesions were rinsed from the left lingual lobe and right middle lobe, the sterile normal saline was slowly injected through biopsy opening, 50 ml for each time, the injecting dose was 200ml, and collected the BALF by 50–100 mmHg negative after lavage. Around 60–90 ml recovery amount was obtained, the collected BALF was filtered to remove mucus, centrifuged at 2,000 rpm for 10 min, and the supernatant was transferred to a glass bottle for the inspection of tumor markers. On the day accepting bronchoscopy detection, 4 ml fasting cubital venous blood was obtained, and separated serum into a glass bottle for tumor markers inspection.
Tumor marker detection
Electrochemiluminescence was performed on CEA and CYFRA21-1. Enzyme-linked immunosorbent assay test was carried out for NSE, the kit was provided by Germany Roche (Mannheim, Germany).
Relevant data obtained in the study were processed and analyzed using Statistical Package for Social Sciences (SPSS) 12.0 statistical software. The parameters were presented as mean ± standard deviation (x–± s), and analyzed using t and χ2 test. P < 0.05 was considered to be statistically significant.
| > Results|| |
Comparisons of tumor markers for BALF
In the BALF of patients in both groups, the concentration of the three tumor markers for observation group were significantly higher than that in the control group. Of which, CYFRA21-1 increased most significantly for about 20 times of the control group. CEA and NSE elevated more than two times compared with the control group. Significant differences existed between the groups (P < 0.01) [Table 2].
|Table 2: Comparisons of three kinds of tumor markers in BALF of the two groups (x̄±s, μg/L)|
Click here to view
Comparisons of serum tumor markers
In the serum of patients in both groups, the concentration of the three tumor markers for the observation group were significantly higher than that of the control group. Of which, NSE and CYFRA-21 increased more significantly for about seven to eight times of the control group. CEA increased more than four times compared with the control group. Significant differences existed between the groups (P < 0.01) [Table 3].
|Table 3: Comparison of three kinds of tumor markers in serum between the two groups (x̄±s, μg/L)|
Click here to view
Comparisons of tumor markers in BALF for patients with pathological type
In BALF, the compared results of CEA concentration among the three kinds of patients with pathological types showed no significant differences (P > 0.05). The comparisons of NSE concentrations in patients with the three pathological type showed that the small cell lung cancer group was significantly higher than that of squamous cell carcinoma and adenocarcinoma groups, the data were statistically significant differences (P < 0.01). The comparisons of the CYFRA21-1 concentration among the patients with the three kinds of pathology showed that the concentrations of squamous cell carcinoma was significantly higher than the small-cell lung and adenocarcinoma groups, the difference was statistically significant (P < 0.01) [Table 4].
|Table 4: Comparisons among the tumor markers in BALF of patients with three kinds of pathological types in the observation group (x̄±s, μg/L)|
Click here to view
Comparisons of tumor markers in the serum of patients with pathological type
In serum, the comparisons of CEA concentration among patients with three kinds of pathology showed that adenocarcinoma group was significantly higher than squamous cell carcinoma and small cell lung cancer groups, the data were statistically significantly different (P < 0.05). NSE concentration comparisons among patients with the three kinds of pathological types showed that small cell lung cancer group was significantly higher than squamous cell carcinoma and adenocarcinoma group, the data had statistically significant difference (P < 0.01). The CYFRA21-1 concentration comparisons among the patients with three kinds of pathology showed that squamous cell carcinoma was significantly higher than small cell lung cancer and adenocarcinoma group, the data had statistically significant differences (P < 0.01) [Table 5].
|Table 5: Comparisons of tumor markers in serum of patients with three kinds of pathological types in the observation group (x̄±s, μg/L)|
Click here to view
| > Discussion|| |
At this stage, lung cancer was a larger disease threat to people's lives and health security, the probability of its incidence was increasing year by year. The earlier the detection of lung cancer, the sooner the effective treatment of lung cancer were carried out, the better it helped to recover after surgery. BALF was a solution mixture of the surface covered BALF and the injected saline. In recent years, BALF was gradually applied to the clinical diagnosis of lung cancer. The relevant medical studies showed that early diagnosis of lung cancer, tumor markers in the bronchial lavage fluid of the patient's body had features such as earlier appearance and higher concentrations compared with tumor markers in serum. The fiberoptic bronchoscopy and bronchoalveolar lavage were operated together, which can be effectively act the early and surrounded type of lung cancers.
In this study, the concentration of tumor markers CEA, NSE, and CYFRA21-1 in BALF and serum for patients with lung cancer and benign lung diseases were examined; the results showed that the concentration differences among the three kinds of tumor markers in the benign and malignant lesions had statistical significance. In the metabolism of cancer cells, CEA could accumulate in the lesions, then released into the blood circulation through accumulating section. According to this theory, CEA concentrations' unconventional changes in BALF occurred earlier and were more significant than that in the serum, which was also confirmed in this research results. But the CEA concentration of lung cancer with different types of pathology in BALF did not reflect the significant difference. Therefore, CEA was more suitable for early judgment of the nature of benign and malignant lung lesions. To further explore whether the pathological markers of different types of lung cancer would vary, this study also examined the concentrations of NSE and CYFRA21-1. NSE was a kind of sugar-metabolizing enzymes, primarily located in the neuroendocrine tissue-derived tumor tissues, which was a specific and sensitive tumor marker for small cell lung cancers. The results of this study showed that BALF and serum NSE concentration of the patients with small cell lung cancers was relatively high. Therefore, NSE can be regarded as highly specific tumor markers for small-cell lung cancer patients. In addition, its pretreatment concentrations were also important factors for predicting tumor progression. CYFRA21-1 constituted lung and acidic proteins of breast epithelial cells. The cancerous epithelial cells released into the blood, importantly influencing lung cancer development, differentiation, and metastasis. Large number of medical reports proved that CYFRA21-1 was one of the important serum tumor markers in patients with NSCLC. CYFRA21-1 expressed the tumor load in body of patients in a certain extent, which had good clinical value for the diagnosis of NSCLCs. The results of this study showed that CYFRA21-1 concentrations of squamous cell carcinoma, both in BALF and serum, were significantly higher than that of small cell lung cancer and adenocarcinoma, suggesting that the two had good correlation.
In summary, the BALF and serum tumor markers detection had a good clinical value and significance in the diagnosis of lung cancer, pathology type, and other aspects. The significance of BALF detection was better than serum detection, which should be introduced in clinical practice.
| > References|| |
Dyzmann-Sroka A, Malicki J. Cancer incidence and mortality in the greater poland region-analysis of the year 2010 and future trends. Rep Pract Oncol Radiother 2014;19:296-300.
Barlési F, Gimenez C, Torre JP, Doddoli C, Mancini J, Greillier L, et al
. Prognostic value of combination of Cyfra 21-1, CEA and NSE in patients with advanced non-small cell lung cancer. Respir Med 2004;98:357-62.
Qin HF, Qu LL, Liu H, Wang SS, Gao HJ. Serum CEA level change and its significance before and after Gefitinib therapy on patients with advanced non-small cell lung cancer. Asian Pac J Cancer Prev 2013;14:4205-8.
Kostovski M, Petrushevska G. Antigenic phenotype of lung carcinomas: Usual spectrum of distribution of thyroid transcription factor-1, cytokeratin 7, cytokeratin 20, and neuron specific enolase-basic immunohistochemical study of 21 cases. Prilozi 2014;35:199-207.
Gao J, Lv F, Li J, Wu Z, Qi J. Serum cytokeratin 19 fragment, CK19-2G2, as a newly identified biomarker for lung cancer. PLoS One 2014;9:e101979.
Heng SC, Chen SC, Morrissey CO, Thursky K, Manser RL, De Silva HD, et al
. Clinical utility of Aspergillus galactomannan and PCR in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies. Diagn Microbiol Infect Dis 2014;79:322-7.
Fiala O, Pesek M, Finek J, Benesova L, Minarik M, Bortlicek Z, et al
. Predictive role of CEA and CYFRA 21-1 in patients with advanced-stage NSCLC treated with erlotinib. Anticancer Res 2014;34:3205-10.
Bastawisy AE, Azzouny ME, Mohammed G, Allah AA, Behiry E. Serum cytokeratin 19 fragment in advanced lung cancer: Could we eventually have a serum tumor marker? Ecancermedicalscience 2014;8:394.
Wu HH, Wang PH, Yeh JY, Chen YJ, Yen MS, Huang RL, et al
. Serum cytokeratin-19 fragment (Cyfra 21-1) is a prognostic indicator for epithelial ovarian cance. Taiwan J Obstet Gynecol 2014;53:30-4.
Burotto M, Thomas A, Subramaniam D, Giaccone G, Rajan A. Biomarkers in early-stage non-small-cell lung cancer: Current concepts and future directions. J Thorac Oncol 2014;9:1609-17.
Zhou F, Chen J, Tao G, Zhu M, Xie W, Cao X. Increased levels of exhaled sICAM1, sVCAM1, and sE-selectin in patients with non-small cell lung cancer. Respir Med 2014;108:1670-6.
Uribarri M, Hormaeche I, Zalacain R, Lopez-Vivanco G, Martinez A, Nagore D, et al
. A new biomarker panel in bronchoalveolar lavage for an improved lung cancer diagnosis. J Thorac Oncol 2014;9:1504-12.
Chen L, Li Q, Zhou XD, Shi Y, Yang L, Xu SL, et al
. Increased pro-angiogenic factors, infiltrating neutrophils and CD163(+) macrophages in bronchoalveolar lavage fluid from lung cancer patients. Int Immunopharmacol 2014;20:74-80.
Chen Z, Xu Z, Sun S, Yu Y, Lv D, Cao C, et al
. TGF-β1, IL-6, and TNF-α in bronchoalveolar lavage fluid: Useful markers for lung cancer? Sci Rep 2014;4:5595.
Yin QQ, Jiao WW, Han R, Jiao AX, Sun L, Tian JL, et al
. Rapid diagnosis of childhood pulmonary tuberculosis by Xpert MTB/RIF assay using bronchoalveolar lavage fluid. Biomed Res Int 2014;2014:310194.
Yin X, Xie L, Chai Y, Fan H, Han X, Feng Z. Surfactant protein b expression in bronchoalveolar lavage fluid of full-term neonates with respiratory distress syndrome. Acta Clin Croat 2014;53:161-5.
Houston KA, Henley SJ, Li J, White MC, Richards TB. Patterns in lung cancer incidence rates and trends by histologic type in the United States, 2004-2009. Lung Cancer 2014;86:22-8.
Kong J, Xu F, He M, Chen K, Qian B. The incidence of lung cancer by histological type: A population-based study in Tianjin, China during 1981-2005. Respirology 2014;19:1222-8.
Bia D, Zócalo Y, Armentano R, Camus J, Forteza Ed, Cabrera-Fischer E. Increased reversal and oscillatory shear stress cause smooth muscle contraction-dependent changes in sheep aortic dynamics: Role in aortic balloon pump circulatory support. Acta Physiol (Oxf) 2008;192:487-503.
Yang H, Mi R, Wang Q, Wei X, Yin Q, Chen L, et al
. Expression of neuron-specific enolase in multiple myeloma and implications for clinical diagnosis and treatment. PLoS One 2014;9:e94304.
Sreenarasimhaiah J, Lara LF, Jazrawi SF, Barnett CC, Tang SJ. A comparative analysis of pancreas cyst fluid CEA and histology with DNA mutational analysis in the detection of mucin producing or malignant cysts. JOP 2009;10:163-8.
Buil-Bruna N, López-Picazo JM, Moreno-Jiménez M, Martín-Algarra S, Ribba B, Trocóniz IF. A population pharmacodynamic model for lactate dehydrogenase and neuron specific enolase to predict tumor progression in small cell lung cancer patients. AAPS J 2014;16:609-19.
Krebs MG, Hou JM, Sloane R, Lancashire L, Priest L, Nonaka D, et al
. Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. J Thorac Oncol 2012;7:306-15.
Woodhams R, Nishimaki H, Fujii K, Kakita S, Hayakawa K. Usefulness of multidetector-row CT (MDCT) for the diagnosis of non-occlusive mesenteric ischemia (NOMI): Assessment of morphology and diameter of the superior mesenteric artery (SMA) on multi-planar reconstructed (MPR) images. Eur J Radiol 2010;76:96-102.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]