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ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 8  |  Page : 39-42

Butyrylcholinesterase: An economical marker of disease activity in oral squamous cell carcinoma before and after therapy


1 Department of Oral Pathology and Microbiology, Sri Aurobindo College of Dentistry, Indore, Madhya Pradesh, India
2 Department of Periodontics, Sri Aurobindo College of Dentistry, Indore, Madhya Pradesh, India

Date of Submission08-Mar-2016
Date of Decision29-Aug-2020
Date of Acceptance04-Sep-2020
Date of Web Publication28-Dec-2020

Correspondence Address:
Gagan Rajesh Jaiswal
FH-325, Scheme Nu-54, Vijay Nagar, Indore - 452 010, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_207_16

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 > Abstract 


Introduction: Biomarkers which can predict disease progression and serve as prognostic indicators are necessary for better management of oral cancer. Studies have shown that Cholinesterase plays an important role in cellular proliferation, differentiation and may have a possible involvement in tumor growth.
Aim and Objective: The present study is aimed to determine the utility of serum Butyrylcholinesterase (BChe) levels as a marker for progression of oral squamous cell carcinoma (OSCC) in relation to the grade of the tumor and to determine if any variation occurred in the levels of BChe before and after therapy.
Materials and Methods: A total of 120 patients were included in the study and divided into two groups as Group A-30 patients (healthy individuals) and Group B-90 cases of histopathologically diagnosed OSCC. The blood sample was collected before surgery, re-collected after the completion of radiotherapy (i.e., 3 and 6 months postsurgery) and analyzed biochemically for the concentration of BCh.
Statistical Analysis: Paired t-test, ANOVA, and post hoc test (Bonferroni) were used for determining the statistical significance.
Results: BChe levels were lower in OSCC (2940.32–1405.50 u/l when compared with controls (11149.60–11243.07 unit/l) and this difference was statistically significant. Postoperatively at 3 months, the serum BChe levels of OSCC patients increased almost two-fold compared to the preoperative values, and this difference was also statistically significant (P = 0.000) After 6 months, these levels further increased but did not reach those of controls.
Conclusion: BChe can be used as an inexpensive, easy to use, noninvasive biomarker for the evaluation of disease-free survival in OSCC patients.

Keywords: Butyrylcholinesterase, oral squamous cell carcinoma, prognosis


How to cite this article:
Jaiswal SG, Jaiswal GR. Butyrylcholinesterase: An economical marker of disease activity in oral squamous cell carcinoma before and after therapy. J Can Res Ther 2020;16, Suppl S1:39-42

How to cite this URL:
Jaiswal SG, Jaiswal GR. Butyrylcholinesterase: An economical marker of disease activity in oral squamous cell carcinoma before and after therapy. J Can Res Ther [serial online] 2020 [cited 2021 Jan 25];16:39-42. Available from: https://www.cancerjournal.net/text.asp?2020/16/8/39/305133




 > Introduction Top


Numerous studies have been carried out in the past to understand the molecular mechanism of cancer. Head and neck squamous cell carcinoma is a heterogeneous disease with complex molecular events visible at the tissue and blood level.[1] Several tumor-specific biomarkers such as vascular endothelial growth factor, and other pro-inflammatory and proangiogenic cytokines have been identified, validated and used for screening, diagnosing and for target therapy of tumors.[2],[3] However, most of these markers are expensive, and hence, their use in clinics becomes difficult.

Cholinesterases are enzymes found in plasma and other body fluids. They can be divided into two categories based on their substrate specificity and susceptibility to inhibitors as acetylcholinesterase or “true cholinesterase” (AChE) and butyrylcholinesterase (BChe) also known as pseudocholinesterase, nonspecific cholinesterase, or simply cholinesterase (BChe). BChe is synthesized in the liver and secreted into plasma.[4] BChe has been documented in various reports as a biochemical marker for cervical cancer. Various studies have been conducted in this direction to understand the nature of various biochemical changes and their impact on tumors.[5] To improve the existing knowledge on BChe this study, we aimed to evaluate the variation occurring in BChe levels before and after surgery in patients of oral squamous cell carcinoma (OSCC) at 3 and 6 months, thus trying to validate the usefulness of BChe as a biochemical marker in OSCC.


 > Materials and Methods Top


An observational study was conducted in the Department of Oral Pathology and Microbiology in association with the Department of Oncology of Sri Aurobindo College of Dentistry, Indore. The study spanned a period of 2 years in which all the patients visiting the oncology department of SAIMS were screened. Biopsy-proven OSCC cases which were classified using TNM staging criteria as stage II, III, and IV were included in the study. Stage I cases were excluded as radiotherapy is not a part of the treatment regimen for these cases. One hundred and thirty-three patients (Stage II (38), III (51), and IV (44)) visiting the oncology department were included in the study. However, contact was lost with 14 patients after surgery and 21 patients could not be followed up after 3 months. Hence, a total of 98 patients could be followed up for 6 months, but for even distribution of sample for statistical analysis, 8 patients were excluded during the analysis; thus, a sample size of 90 OSCC patients was available for the statistical analysis. These patients were of either sex between 26 and 75 years and were divided into three groups of equal size (n = 30) according to clinical staging (Stage II, Stage III, and Stage IV), 30 age-matched healthy controls that underwent an oral examination to rule out all possible benign or malignant oral diseases were taken as controls.

Exclusion criteria

For cases

Oral cancers, which were not squamous cell carcinomas, recurrent cases of squamous cell carcinoma, patients with any other systemic illness, especially involving the liver, patients on immunosuppressant, patients on long-term medication, and chronic alcoholics.

For control

Patients with any other systemic illness such as diabetes mellitus, hypertension, or any disorder involving the liver and patients on long-term medication for any reason.

Method

Blood sample was collected before surgery and analyzed biochemically for the concentration of BChe. Blood sample was re-collected after the completion of radiotherapy at 3 and 6 months after surgery and analyzed biochemically for the concentration of BChe.

Statistical analysis

The data were analyzed using statistical software SPSS version 17.0 (IBM). Statistical analyses included both descriptive and inferential methods. Continuous variables were expressed as mean ± standard deviation (SD).

Paired t-test was used to identify the significance of mean differences in serum BChe levels. One way analysis of variance (ANOVA) was carried out to identify the significance of mean differences in serum BChe among all (controls and cases) subjects preoperatively and among cases with different clinical staging in OSCC postoperatively at 3 and 6 months. The post hoc test was also carried out to observe the multiple comparisons by using the Bonferroni test. The probability value P = 0.05 was considered significant, while P = 0.001 was considered as highly significant.


 > Results Top


This observational study included 120 subjects, of which 63 were male (52.5%) and 57 were female (47.5%). The mean age and SD of all subjects were 43.39 ± 14.79 years.

The mean pretreatment serum BChe levels were higher in controls as compared to OSCC. Among the OSCC stages, they were highest in Stage II, followed by Stage IIIand Stage IV OSCC patients, as shown in [Table 1]. This differences were highly significant (P = 0.000). On comparing the mean serum BChe levels postoperative at 3 months, they were the highest in stage II followed by cases of Stage III and stage OSCC patients, and this was also highly significant (P = 0.000) [Table 2]. The post hoc test was identified by using the Bonferroni test to judge the multiple comparisons, which was highly significant (P = 0.000).
Table 1: Comparison of butyrylcholinesterase differences preoperatively among cases and controls

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Table 2: Comparison of butyrylcholinesterase levels postoperatively among clinical stages of oral squamous cell carcinoma at 3 months

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The postoperative values at 6 months were the highest for Stage II followed by Stage III and stage IV; this difference was also highly significant (P = 0.000) [Table 3]. The posttreatment BChe levels had increased as compared to the pretreatment levels but did not reach baseline that is that of controls [Table 4].
Table 3: Comparison of butyrylcholinesterase levels posttreatment at 6 months among different clinical staging in oral squamous cell carcinoma

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Table 4: Comparison of butyrylcholinesterase levels between pretreatment and post operatively at 3 and 6 months in oral squamous cell carcinoma patients

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 > Discussion Top


Biochemical changes in blood and other body fluids provide an easy, simple yet substantial pathway for understanding the changes that may, in some way, be responsible for the development or progression of malignancy. Several studies have been carried out on tumor tissue to explore various tumor markers that may serve as adjuvant in diagnosis, prognosis, and treatment planning.[6],[7],[8],[9],[10],[11],[12],[13]

OSCC is the most commonly encountered malignancy in the head and neck region. Its early detection and therapy help to improve the quality of life of the patient and the overall life expectancy. Several biochemical markers have been identified in the past, which would help diagnosis and prognosis. The important characteristics of a good marker include: (1) it should be less expensive, (2) should be easily available, (3) tests should be easily repeatable, (4) should be able to differentiate between normal and pathologic conditions, and (5) should be less explored. BChe is extensively used in forensic medicine as a treatment modality for organophosphorous poisoning. Its utility as a marker has been extensively studied in cervical cancers but is relatively less explored in the head-and-neck tumors. Moreover, it is less expensive as compared to other markers and is present in body fluids normally. It is available in the market in the form of ready to use kits, which are inexpensive and hence can be used routinely in clinical practice. As BChe could satisfy most of the requirement of a good marker hence we aimed to evaluate if it could be used as a biochemical marker for OSCC.

It was found that the BChe levels in controls were higher than that in OSCC cases. We also found that There was a consistent decrease in mean BChe levels with increasing grades of carcinoma. The mean pretreatment serum BChe levels were lowest in Stage IV, followed by Stage III and stage II OSCC patients. The mean differences of BChe levels among different stages in OSCC patients and controls were highly significant (P = 0.000) and strongly different for all groups [Table 1]. This was in accordance with Chougle et al.[14] who found BChe levels were lower than normal in all head and neck tumors, but contrast to that of Prabhu et al.[15] who found increasing levels of BChe with increasing grades of tumor.

We re-evaluated on re-evaluating the levels of BChe in OSCC at regular intervals after surgery and radiotherapy at 3 months and it was found that the BChe levels had started increasing compared to those recorded before surgery. These values were highest in stage II and lowest in stage IV. This could be due to the debulking of the tumor and hence indicative of the body returning to normalcy, however due to incomplete recovery the levels were still lower than normal. We re-evaluated On re-evaluating the serum BChe levels at 6 months and it was found observed that the Bche levels, which were low preoperatively increased gradually postoperatively but did not reach that of controls [Table 4]; this was in accordance with that studied by Chougle et al.[14] who also found that serum BChe levels, which were low in all patients with epithelial malignancies like head and neck and uterine cervix cancers, started increasing after radiotherapy. This finding has also been substantiated by Ghooi et al.[16] who studied pseudocholinesterase levels in various malignancies and found that the levels were lower than normal in advanced malignancies with hepatic metastasis. Our results were also similar to that stated by Sen et al.[17] who studied the PCHE levels in healthy individuals and compared them with those of leukoplakia and OSCC, they found that the levels decreased from leukoplakia to OSCC and hence said that it could definitely be used as a diagnostic marker.

We wanted the study aimed to follow-up our patients for a longer duration, but due to time constraints and other factors, it was not possible were unable to do so. Commenting on prognosis becomes difficult in 6 months, but we it can definitely be said that the positive results encountered by us definitely validates the utility of BChe as a biochemical marker to evaluate disease progression as these levels will increase with a decrease in tumor load but will decrease with increase in tumor aggressiveness and in probable metastasis as already proven by Chougle et al.[14]


 > Conclusion Top


Thus, it can be concluded that serum BChe can definitely be used as an inexpensive prognostic marker helping the clinician to evaluate the disease activity at regular intervals as its values will start decreasing with an increase in disease aggressiveness, thereby giving an indication of probable recurrence of the disease.

Limitations of the study

Limited follow-up of 6 months and unicentric nature of the study.

Future prospects

A larger sample size with a follow-up of 3 years is recommended, which will further validate the utility of this marker and reduce the financial burden on patients suffering from OSCC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Jaiswal G, Jaiswal S, Kumar R, Sharma A. Field cancerization: Concept and clinical implications in head and neck squamous cell carcinoma. J Exp Ther Oncol 2013;10:209-14.  Back to cited text no. 1
    
2.
Jaiswal SG, Gadbail AR, Chaudhary MS, Jaiswal GR, Gawande M. Correlation of serum levels of vascular endothelial growth factor with TNM staging, histopathologic grading, and surgical therapy for oral squamous cell carcinoma. Quintessence Int 2011;42:771-9.  Back to cited text no. 2
    
3.
Chen Z, Malhotra PS, Thomas GR, Ondrey FG, Duffey DC, Smith CW, et al. Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. Clin Cancer Res 1999;5:1369-79.  Back to cited text no. 3
    
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Nese Cokugras A. Butyrylcholinesterase: Structure and physiological importance. Turk J Biochem 2003;28:54-61.  Back to cited text no. 4
    
5.
Bradamante V, Smigovec E, Bukovic D, Geber J, Matanic D. Plasma cholinesterase activity in patients with uterine cervical cancer during radiotherapy. Coll Antropol 2000;24:373-80.  Back to cited text no. 5
    
6.
Bergmeyer HU. Cholinesterase. In: Whittaker M, editor. Methods of Enzymatic Analysis, Enzyme 2: Esterases, Glycosidases, Lyases, Ligases. 3rd ed., Vol 4. Weinheim: Verlag Chemie GmbH; 1984. p. 63-74.  Back to cited text no. 6
    
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Oyama T, Kawamoto T, Matsuno K, Osaki T, Matsumoto A, Isse T, et al. A case-case study comparing the usefulness of serum trace elements (Cu, Zn and Se) and tumor markers (CEA, SCC and SLX) in non-small cell lung cancer patients. Anticancer Res 2003;23:605-12.  Back to cited text no. 7
    
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Yanagitani N, Kaira K, Sunaga N, Naito Y, Koike Y, Ishihara S, et al. Serum amylase is a sensitive tumor marker for amylase-producing small cell lung cancer? Int J Clin Oncol 2007;12:231-3.  Back to cited text no. 8
    
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Pietropaoli MP, Damron TA, Vermont AI. Bone metastases from squamous cell carcinoma of the head and neck. J Surg Oncol 2000;75:136-41.  Back to cited text no. 9
    
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Chougule A, Hussain S, Agarwal DP. Serum CEA levels as an index of disease activity in various carcinogenic conditions. J Clin Radiother Oncol 2004;4:44.  Back to cited text no. 10
    
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Chougule A. Management of malignancies by radiotherapy and role of biochemical parameters. Asian J Exp Sci 1999;13:39.  Back to cited text no. 11
    
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Chougule A. Role of some biochemical markers in management of malignancy. In: Goel SC, editor. Advances in Radiation Biology and Peace. Uttar Pradesh: Utter Pradesh Zoological Society Publishers; 1999. p. 69.  Back to cited text no. 12
    
13.
Hoffmann RR, Yurgel LS, Campos MM. Endothelins and their receptors as biological markers for oral cancer. Oral Oncol 2010;46:644-7.  Back to cited text no. 13
    
14.
Chougule A, Hussain S, Agarwal DP. Prognostic and diagnostic value of serum pseudocholinesterase, serum aspartate transaminase, and serum alinine transaminase in malignancies treated by radiotherapy. J Cancer Res Ther 2008;4:21-5.  Back to cited text no. 14
    
15.
Prabhu K, Naik D, Ray S, Vadiraj, Rao A, Kamath A. Significance of serum butyrylcholinesterase levels in oral cancer. Australas Med J 2011;4:374-8.  Back to cited text no. 15
    
16.
Ghooi AM, Malviya GM, Kashyab A. A comparative study of LDH and PCHE in sera of cancer patients – A prelimnary report. Indian J Cancer 1980;17:31.  Back to cited text no. 16
    
17.
Sen R, Sur R, Dasgupta R, Mazumder GC. Serum pseudocholinesterase activity & protein bound fucose level in oral malignancy. Indian J Cancer 1987;24:242-50.  Back to cited text no. 17
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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