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ORIGINAL ARTICLE
Year : 2012  |  Volume : 8  |  Issue : 6  |  Page : 123-125

Salivary lactate dehydrogenase levels in oral leukoplakia and oral squamous cell carcinoma: A biochemical and clinicopathological study


1 Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of Dental Sciences, Nitte University, University Enclave, Deralakatte, Mangalore, Karnataka, India
2 Department of Biochemistry, Central Research Laboratory Nitte University, University Enclave, Deralakatte, Mangalore, Karnataka, India

Date of Web Publication24-Jan-2012

Correspondence Address:
Shishir Ram Shetty
Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of Dental Sciences, Nitte University, University Enclave, Deralakatte, Mangalore - 575 018, Karnataka
India
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Source of Support: ICMR-STS 2009 21/KA/ABS-11/09-BMS, Conflict of Interest: None


DOI: 10.4103/0973-1482.92226

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 > Abstract 

Background: Oral cancer is the third most common form of malignancies in India. In many cases it develops at the site of premalignant lesion. Transformation of normal tissue to premalignant lesion and further to oral cancer results in alteration in glycolytic pathway and hence the lactate dehydrogenase levels. Therefore, a study was carried out to determine the changes in the salivary alterations in lactate dehydrogenase (LD) levels oral leukoplakia (OL) and oral cancer (OC).
Methods: Seventy-five patients reporting to department of oral medicine and radiology, were enrolled into the study which includes 25 patients each of oral leukoplakia, 25 of oral cancer and 25 healthy controls (HC). Unstimulated whole saliva measuring 1 mL will be collected from each of these patients by spit method in centrifuged and evaluated for LDH levels using the standard kit method. The data obtained were subjected to statistical analysis using the SPSS software version 17.
Results: The mean salivary lactate dehydrogenase levels were higher in males in comparison to females in all three study groups OL, OC and HC. The salivary lactate dehydrogenase levels in the controls group, oral leukoplakia group and oral cancer were 79.50 ± 4.67 IU/L, 136.46 ± 3.36 IU/L and 148.77 ± 4.83 IU/L, respectively. There was a significant difference in the mean salivary levels of the above groups.
Conclusion: Salivary lactate dehydrogenase levels are consistently higher in oral precancer and cancer hence it could be future marker

Keywords: Oral cancer, oral leukoplakia, salivary lactate dehydrogenase


How to cite this article:
Shetty SR, Chadha R, Babu S, Kumari S, Bhat S, Achalli S. Salivary lactate dehydrogenase levels in oral leukoplakia and oral squamous cell carcinoma: A biochemical and clinicopathological study. J Can Res Ther 2012;8, Suppl S2:123-5

How to cite this URL:
Shetty SR, Chadha R, Babu S, Kumari S, Bhat S, Achalli S. Salivary lactate dehydrogenase levels in oral leukoplakia and oral squamous cell carcinoma: A biochemical and clinicopathological study. J Can Res Ther [serial online] 2012 [cited 2019 Dec 13];8:123-5. Available from: http://www.cancerjournal.net/text.asp?2012/8/6/123/92226


 > Introduction Top


The term oral cancer encompasses all malignancies that originate in the oral tissues and remains a major public health problem throughout the world as an important case of poor health and illness. [1] The disease is characterized by high degree of morbidity and mortality (about 50%). [2] Head and neck cancer account for 9.8% of the estimated 644,600 incidental cancer cases in India. [3] Oral Squamous cell carcinoma (OSCC) is a multistage process, from normal to dysplastic cells (precancerous lesions) and ultimately to squamous cell carcinoma. [4] Oral leukoplakia (OL) is the most commonly occurring precancerous lesion (OPC) of the oral cavity representing 85% of such lesions. [4] The development of cancer is associated with a high glycolytic activity with a shift from aerobic to anaerobic glycolysis. With the increase in the glycolytic activity the concomitant increase in lactate dehydrogenase (LDH) enzyme may be reflected in certain tissues. [5] Studies in the past have been carried out to evaluate the LDH isoenzymes in patients with leukemia, wherein an elevated enzyme level was observed. [5] However, another study involving LDH isoenzymes ratio concluded that there was no significant alteration in ratio of patients with oral cancer or precancer. [6] When biopsy tissue LDH isoenzyme ratios of oral cancer (OC), oral submucous fibrosis (OSMF) and oral leukoplakia with healthy oral tissues, it was found that the ratios were significantly altered in OC and OSMF. [7] Salivary LDH levels have been rarely studied in OC and OPC. The aim of our study was to evaluate the LDH levels in oral leukoplakia and oral cancer using the relatively noninvasive saliva as the diagnostic tool.


 > Materials and Methods Top


The study involved 75 subjects with age range of 20 to 65 years reporting to the Department of Oral Medicine and Radiology. Twenty-five clinically diagnosed and histopathologically confirmed cases of oral leukoplakia formed the first group (OL). Twenty-five histopathologically confirmed cases of oral cancer comprised the second group (OC). Twenty-five age and sex matched healthy controls formed the third group (HC). Each of the study groups had five female subjects. Patients with a history of myocardial infarction, liver disease, renal disease and muscle dystrophy were excluded from the study. Patient with history of previous malignancy were also excluded from the study. Unstimulated saliva samples were collected from each of the patients by the spit method in the calibrated test tube. Care was taken to see that the volunteers did not consume food, smoke or chew gum at least one hour before the saliva collection procedure. The samples were diluted in 1:1 ratio with saline and assayed using the standard kit and measured sphectrophotometrically at 340 nm (results multiplied by factor 2, this procedure measures total LDH levels irrespective of its tissue or organ origin). The LDH concentrations were expressed in terms of IU/L. The data were analyzed by using SPSS statistical software version (17). One-way ANOVA was used to compare the data among the groups and the difference was considered to be statistically significant if 'P' values were 0.05 or less.


 > Results Top


Mean salivary LDH level in HC, OL and OC groups were 79.50 ± 4.67 IU/L, 136.46 ± 3.36 IU/L and 148.77 ± 4.83 IU/L, respectively. The mean salivary LDH levels in male subjects in HC, OL and OC groups were 90.67 ± 4.06 IU/L, 145.69 ± 3.72 IU/L and 152.67 ± 4.33 IU/L, respectively. The mean salivary LDH levels of female subjects in the corresponding groups were 68.34 ± 3.90 IU/L, 127.23 ± 3.33 IU/L and 144.87± 4.11 IU/L, respectively [Figure 1]. The salivary LDH levels were significantly higher (P=0.01) in males when compared to female subjects in all three study groups. There was a highly statistically significant difference (P=0.001) when the mean saliva LDH levels of group HC was compared to group OL. On comparison of the mean salivary LDH levels of group OL to group OC there was a statistically significant difference (P=0.0001). When mean salivary LDH levels of group HC were compared to group OC there was a very high significant difference [Figure 2].
Figure 1: Mean salivary LDH levels in the study groups

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Figure 2: Mean salivary LDH levels

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 > Discussion Top


Lactate dehydrogenase has been described as an ubiquitous enzyme that plays a very important role in the diagnosis of the pathologic process. [8] Studies on serum, tissue and urine LDH levels in detection of various disorders have been conducted in the recent past. [9],[10],[11] Saliva testing, has been promoted as a noninvasive alternative to serum testing in diagnosis and prognosis of oral cancer that may be an effective modality for diagnosis and for prognosis prediction of oral cancer. [12] This study evaluated the LDH levels in saliva of OC, OL patients and healthy controls. In our study, male subjects had relatively higher salivary LDH levels compared to female subjects. This pattern is observed in serum but has not been highlighted in saliva. [13] In our study, salivary LDH levels were higher in OC patients. Studies have reported elevated tissue, salivary and serum LDH levels in different types of malignancies. [9]

A study intended to evaluate LDH as a prognostic marker for histiocytic lymphoma showed that the 2-year-survival rates of patients with serum LDH levels greater than 500 U was only 13% when compared to 67% of those patients whose LDH levels were below 500 U. [9] In another study, salivary LDH levels of 25 otherwise healthy OC patients and 25 healthy age and sex matched controls were evaluated. Salivary LDH levels were significantly higher in oral cancer patients. [10] An immunohistochemical evaluation of LDH in various type of malignant cells showed that irrespective of the malignancy, the levels were higher than that of normal cells. [14] In a study, involving five salivary parameters, elevated salivary LDH levels were observed in tongue cancer patients when compared to healthy controls. [15] Salivary LDH has been considered as reliable molecular marker for oral cancer in some studies. [16] A study examining the effects of radioactive I 131 on salivary gland activity, saliva composition, oxidative profile and related oral discomfort complaints following thyroidectomy due to carcinoma of thyroid gland showed elevated levels of salivary LDH. [17]

In our study, there was a significant difference in the salivary LDH levels between HC and OL subjects. Similar studies involving OL and Oral submucous fibrosis were carried out in Danish and South Indian population yielding similar results. [7] Recent studies have revealed that the salivary LDH levels significantly vary after smoking. [18],[19]

In conclusion, salivary LDH levels could be a reliable maker for oral cancer; thus, alterations in salivary LDH levels could be a crucial factor in pathogenesis of oral cancer.

 
 > References Top

1.Prabhu SR, Johnson NW, Daftary DK, Wilson DF. Oral Diseases in the Tropics. 1 st ed. USA: Oxford University Press; 1992.  Back to cited text no. 1
    
2.Nagler RM, Barak M, Ben Aryeh H, Peled M, Filatov M, Laufer D. Early diagnostic and treatment monitoring role of cyfra 21-1 and TPS in oral squamous cell carcinoma. Cancer 1999;35:1018-25.  Back to cited text no. 2
    
3.Tavani A, Franceschi S, Levi F, Corrao G, Negri E. Epidemiology and prevention of oral cancer. Oral Oncol 1997;33:302-12.  Back to cited text no. 3
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4.Neville BW, Damm DD, Allen CM, Bouquot JE. Oral and maxillofacial pathology. 2 nd ed. Philadelphia: Saunders; 2002.  Back to cited text no. 4
    
5.Zondag HA, Klein F. Clinical applications of lactate dehydrogenase isoenzymes: Alteration in malignancy. Ann N Y Acad Sci 1968;151:578-80.  Back to cited text no. 5
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6.Langavad E, Roed PB. Studies in oral leukoplakia. Lactate dehydrogenase isoenzyme pattern in oral leukoplakia. Acta Pathol Microbiol Scand 1969;75:193-200.  Back to cited text no. 6
    
7.Langavad E, Zachariah J, Pindborg JJ. Lactate dehydrogenase, isoenzyme pattern in leukoplakia, submucous fibrosis and carcinoma of the oral mucosa in south Indians. Acta Pathol Microbial Scand 1970;78:509-15.  Back to cited text no. 7
    
8.Nagler RM, Lischinsky S, Diamond E, Klein I, Reznick AZ. New insights into salivary lactate dehydrogenase of human subjects. J Lab Clin Med 2001;137:363-9.  Back to cited text no. 8
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9.Schneider RJ, Seibert K, Passe S, Little C, Gee T, Lee BJ, et al. Prognostic significance of serum lactate dehydrogenase in malignant lymphoma. Cancer 1980;46:149-53.  Back to cited text no. 9
    
10.Shpitzer T, Bahar G, Feinmesser R, Nagler RM. A comprehensive salivary analysis for oral cancer diagnosis. J Cancer Res Clin Oncol 2007;133:613-7.  Back to cited text no. 10
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11.Kehrer G, Blech M, Kallerhoff M, Bretschneider HJ. Urinary LDH-release for evaluation of postischemic renal function. J Mol Med 1989;67:477-85.  Back to cited text no. 11
    
12.Nagler RM. Saliva as a tool for oral cancer diagnosis and prognosis. Oral Oncol 2009;45:1006-10.  Back to cited text no. 12
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13.Henry JB. Clinical diagnosis and management by laboratory methods. 1 st ed. Philadelphia: WB Saunders and Company; 1979.  Back to cited text no. 13
    
14.Pan L, Xu J, Isaacson PG. Cellular H- and M-type lactate dehydrogenase (LDH) isoenzymes and tumour diagnosis-an immunohistochemical assessment. J Pathol 1991;163:53-60.  Back to cited text no. 14
    
15.Shpitzer T, Hamzany Y, Bahar G, Feinmesser R, Savulescu D, Borovoi I, et al. Salivary analysis of oral cancer biomarkers. Br J Cancer 2009;101:1194-8.  Back to cited text no. 15
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16.Markopoulos AK, Michailidou EZ, Tzimagiorgis G. Salivary markers for oral cancer detection. Open Dent J 2010;4:172-8.  Back to cited text no. 16
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17.Shalom SI, Durleshter L, Segal E, Nagler RM. Sialochemical and oxidative analyses in radioactive I131-treated patients with thyroid carcinoma. Eur J Endocrinol 2008;158:677-81.  Back to cited text no. 17
    
18.Reznick AZ, Hershkovich O, Nagler RM. Saliva - A pivotal player in the pathogenesis of oropharyngeal cancer. Br J Cancer 2004;91:111-8.  Back to cited text no. 18
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19.Greabu M, Battino M, Totan A, Mohora M, Mitrea N, Totan C, et al. Effect of gas phase and particulate phase of cigarette smoke on salivary antioxidants. What can be the role of vitamin C and pyridoxine? Pharmacol Rep 2007;59:613-8.  Back to cited text no. 19
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