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Journal of Cancer Research and Therapeutics
Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI)
ISSN: 0973-1482 EISSN: 1998-4138
Vol. 4, Num. 1, 2008, pp. 21-25

Journal of Cancer Research and Therapeutics, Vol. 4, No. 1, January-March, 2008, pp. 21-25

Original Article

Prognostic and diagnostic value of serum pseudocholinesterase, serum aspartate transaminase, and serum alinine transaminase in malignancies treated by radiotherapy

Arun Chougule, Sofia Hussain, Prasad Agarwal Dwaraka

Department of Radiotherapy, SMS Medical College and Hospital, Jaipur
Correspondence Address: II - 38, Gandhinagar, Jaipur - 302 015
arunchougle@rediffmail.com

Code Number: cr08006

Abstract

Background: There is substantial evidence that environmental factors cause or accelerate the onset of malignancy. Environmental factors, due to the presence of many pollutants and carcinogenic agents, alter cellular growth, which leads to biochemical changes in the blood.
Materials and Methods:
In the present study, we estimated serum pseudocholinesterase (PCHE), serum aspartate transaminase (AST), and serum alanine transaminase (ALT) in 92 patients with head and neck cancer and 71 patients with cancer of the uterine cervix; all of them were patients attending our department for radiation therapy. We also estimated PCHE, AST, and ALT levels in 30 healthy normal individuals. The estimations in cancer patients were done before the start of radiotherapy, midway through radiotherapy (30 Gy dose), at the end of radiotherapy, and during subsequent monthly follow-up visits over a period of at least 6 months.
Results and d0 iscussion:
We have observed that the PCHE levels were lower (31-49% of normal value) in all patients with malignancies, except in those with stage II head and neck cancers. We also found that the levels start increasing as radiotherapy progresses. The patients with no detectable/visible disease activity at 6 months follow-up showed PCHE values in the normal range. Similarly, the AST and ALT values were much higher (138-229% of normal value) in all the malignant cases as compared to the normal healthy individuals. The values decrease and approach normal levels as radiotherapy progresses and, in 92% of head and neck cancer cases [stages IIA, IIB, and IIIA] with no disease activity, the PCHE, AST, and ALT were normal or near normal; the corresponding figure in cancer cervix cases was 89%. From the present study we conclude that PCHE, AST, and ALT can be used as good prognostic biochemical tumor markers in the management of malignancies of the head and neck and uterine cervix.

Keywords: Biochemical markers, malignancy, pseudocholinesterase, radiotherapy, serum alanine transaminase, serum aspartate transaminase

Introduction

With the advances in molecular biology and clinical enzymology, it is now clear that malignancy can be explained on the basis of biochemical changes in the tissue. Its relevance can be addressed in several categories; for example molecular level knowledge provides a better understanding of the chemical processes responsible for malignancy. Concrete or better corrective measures can be taken to check the malignancy. Biochemical markers as an adjunct for diagnosis and prognosis of disease have either been developed or are under development. Literature scan reveals that a large number of parameters have been studied to develop a reliable marker, but efforts so far have met with only limited success. The ideal biochemical marker for different types of malignancies must have the following characteristics:
  1. It should be produced by the tumor cell and be readily detectable in body fluids.
  2. It should not be present in the healthy or in those with benign diseases.
  3. It should be present frequently and early enough in the development of malignancy so that it can be useful in screening.
  4. It should directly reflect the bulk and stage of malignancy.
  5. It should be detectable even before there is clinical evidence of tumor.
  6. It should correlate with the results of anticancer therapy.

At present no single biochemical marker is capable of meeting all these criteria.

The present study attempted to find out the role of some of the biochemical markers, i.e., serum pseudocholinesterase (PCHE), serum aspartate transaminase (AST), and serum alanine transaminase (ALT), in malignancies of the head and neck and the uterine cervix; these two major malignancies in the males and females in India comprise the major bulk of the malignancies (about 30% and 25%, respectively).

Materials and Methods

In present study, we estimated serum PCHE, AST, and ALT levels in 30 normal healthy individuals and have taken those values as representing the normal level. We also measured the levels in blood samples from patients with biopsy-proven cancer of the head and neck ( n = 92) and cervix ( n = 71) who were attending our department for radiation therapy. The levels were estimated before start of therapy (BT); midway (MT) through therapy, i.e., after delivery of 30 Gy radiation dose; at the end (CT) of radiation therapy; and during subsequent monthly follow-up visits over at least 6 months.

Patients with malignancies of the head and neck and cervix were treated with a telecobalt unit at 80 cm SSD with 200 cGy/F dose up to a total dose of 60-70 Gy in 6-7 weeks. All the patients were assessed weekly for tumor status till the completion of therapy and were advised to come for regular monthly follow-up thereafter.

For estimation of levels of the biochemical markers, 5 cc of venous blood was collected, serum was separated, and estimation of PCHE, AST, and ALT was done according to standard procedures.

Results

The observed levels of PCHE in cases of cancer of the head and neck and cervix are given in [Table - 1],[Table - 2]. The results of the statistical analysis to find the significance of PCHE, AST, and ALT levels at start of therapy, midway through therapy, and at the end of therapy in head and neck cancer cases and in carcinoma cervix cases is tabulated in [Table - 7],[Table - 8], respectively. It is observed that the PCHE levels are significantly lowered in all patients suffering from head and neck cancers (except stage II) and cancer cervix as compared to controls, and a statistically significant rise was observed as therapy progressed. It is further observed that in all cases of cancer of the head and neck and cancer cervix, the AST and ALT levels are higher than the normal levels and they approach the normal levels as therapy continues, which is statistically significant.

Discussion

Extensive biochemical studies have been carried out on tumor tissue and peripheral blood to explore the etiology of cancers and to establish tumor markers. [1],[2] Warburg [3],[4] has reported that cancer tissue exhibited a greater rate of aerobic glycolysis than normal tissue and for the first time suggested the study of biochemical markers in neoplasms. Authors [5],[6],[7],[8],[9],[10] have also studied serum alkaline phosphate, serum amylase, serum lactate dehydrogenase, CEA, serum calcium, serum magnesium, serum copper, serum zinc, and the copper/zinc ratio in various malignancies as possible diagnostic and prognostic biochemical markers. We did not find any study in literature on the role of AST and ALT in malignancies of the head and neck and cervix.

The process of transamination was first observed by Needhan. [11] Since then, AST and ALT have received wide application for diagnosis and prognosis. Increased levels of AST and ALT are commonly found in liver diseases, particularly in infective hepatitis. Pryse-Davis [12] reported that in 50% of cancer patients with liver metastasis, the AST activity was elevated, and very high values were noted in patients with massive secondary involvement of the liver accompanied by extensive liver cell necrosis. Wilkinson [13] reported that primary tumors of the large intestine were associated with elevated transaminase activity.

Cholinesterase is an enzyme which hydrolyses ester of choline to give choline and the acid. Two types have been distinguished: true cholinesterase and pseudocholinesterase. Cholinesterase is the best indicator available to assess the degree of exposure in different types of environmental stresses. A little literature is available regarding its values as a tumor marker. Ghooi et al. [14] studied PCHE levels in various malignancies and reported low PCHE levels in advanced malignancies with hepatic metastases. Sen et al . [15] studied PCHE levels in healthy persons with oral leukoplakia and in patients with oral carcinoma; he observed diminishing activity with advancement of cancer and suggested PCHE as a definite biochemical marker in the diagnosis and prognosis of oral malignancy.

In the present study, PCHE levels in 30 normal healthy individuals were estimated in addition to that in 92 head and neck cancer and 71 cancer cervix patients; levels were checked before start of radiotherapy, midway between radiotherapy, at end of radiotherapy, and at subsequent monthly follow-ups for 6 months. The levels in malignancy were lower than that in normal subjects. The levels in normal subject were 236.3 ± 61.0 units, whereas the levels were 256.3 ± 66.2, 163.6 ± 18.8 (69% of normal value), and 120.4 ± 17.8 (49% of normal value) units in stages IIA, IIB, and IIIA head and neck cancers, respectively [Table - 1]. As radiotherapy progressed the levels rose and returned to normal levels in patients with no detectable/ visible disease activity. The results of the statistical analysis, given in [Table - 7], indicates that the PCHE levels are significantly lower than the normal levels, and the variation in levels after treatment has significance for the prognosis. Similarly, the PCHE levels were lower than the normal at all the stages of cancer cervix [Table - 2]. The statistical analysis given in [Table - 8] indicates the role of PCHE in malignancy of the cervix. Therefore, serum PCHE estimation can be used as a good diagnostic and prognostic tumor marker in the management of malignancies of the head and neck and the cervix.

Serum AST and ALT levels ranged from 5.0-15.5 and 6.0-19.5 IU/l, respectively, in normal subject. Mild to moderate rise of AST and ALT levels was observed in both malignancy of the head and neck and of the cervix [Table - 3],[Table - 4],[Table - 5],[Table - 6]. The levels showed progressive rise with increasing severity of the disease. The most important feature is that the AST levels after 6 months follow-up were 11.3 ± 0.9, 12.2 ± 1.5, 11.4 ± 1.2, and 10.4 IU/l in NED patients of head and neck cancers stage IIA, IIIA, and IIIB, respectively, indicating their significance as markers. The levels were 21.3 ± 0.2, 24.7 ± 0.9, and 21.3 ± 0.1 IU/l in residual tumors of stage IIA, IIB, and IIIA. Similar trends were observed in ALT levels. The statistical analysis given in [Table - 7],[Table - 8] indicates good statistical significance. It does not have diagnostic value but can be used as a prognostic marker. From the present study we observe that PCHE, AST, and ALT can be used as tumor markers in the management of malignancy of the head and neck and the uterine cervix.

References

1.Kshivets OM, Merabishvili VM, Pospelov DA, Kshivetz MS, Gusev VS. , Plaksin IT, et al . The value of biochemical indices of blood in early diagnosis of gastric cancer. Klin Khir 1992;8:16.  Back to cited text no. 1    
2.Hansen M. Serum tumor markers in lung cancer. Eur J Cancer Prev 1993;29A:483.  Back to cited text no. 2    
3.Warburg O. The metabolism tumor (translated by Dickens F). Constable and Co. Ltd.: London; 1930. p. 35.  Back to cited text no. 3    
4.Warburg O, Christian W. Garungsferonen le in blut serum von tumor- ratten. Biochem Itschr 1943;314:399.  Back to cited text no. 4    
5.Hussain S, Chougule A, Singh PP. Estimation of serum amylase levels in patients of cancer head and neck and cervix uterus treated by radiotherapy. Indian J Clin Radiother Oncol 1992;7:24.  Back to cited text no. 5    
6.Chougule A, Hussain S. Prognostic value of alkaline phosphatase in management of carcinoma head and neck and cervix. Indian J Clin Radiother Oncol 1997;12:57.  Back to cited text no. 6    
7.Chougule A, Hussain S. Significance of serum copper, zinc and copper/zinc ratio in cancer head and neck and cervix uterus treated with radiotherapy. Asian J Exp Sci 1998;13:29.  Back to cited text no. 7    
8.Chougule A. Role of some biochemical markers in management of malignancy. Chapter in book "Advances in Radiation Biology and Peace. In : Goel SC, editor. 1999. p. 69.  Back to cited text no. 8    
9.Chougule A. Management of malignancies by radiotherapy and role of biochemical parameters. Asian J Exp Sci 1999;13:39.  Back to cited text no. 9    
10.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    
11.Needhan DM. Quoted from "An introduction to diagnostic enzymology: In : Wilkinson JH, editor. Edward Arnold Pub. Ltd: London; 1960.  Back to cited text no. 11    
12.Pryse-Davies J, Wilkinson JH. Diagnostic value of serum Transaminase activity in hepatic and gastro intestinal disease. Lancet 1958;1:1249-53.  Back to cited text no. 12  [PUBMED]  
13.Wilkinson JH. An introduction to diagnostic enzymology. Pub Edward Arnold Pvt Ltd: London; 1962. p. 187.  Back to cited text no. 13    
14.Ghooi AM, Malviya GM, Kashyab A. A comparative study of LDH and PCHE in sera of cancer patients - preliminary report. Indian J Cancer 1980;17:31.  Back to cited text no. 14    
15.Sen R, Sur R, Dasgupta R, Mazumdar GL. Serum pseudocholinestearse activity and protein bound fucose level in oral malignancy. Indian J Cancer 1987;24:242.  Back to cited text no. 15    

Copyright 2008 - Journal of Cancer Research and Therapeutics


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