Study of role of serum LDH in carcinoma of breast as a prognostic biomarker

 

 

Abstract               Background: Carcinoma breast is commonest cancer in urban and rural females in India. Presently, India already has one of the worst survivals from breast cancer, in the world. Cancer is a group of diseases that cause cells in the body to change and grow out of control. While considering the strategy of treatment, accurate estimation of prognosis in breast cancer is very important. Diagnosis at advanced stages of disease contributes to the high mortality rate among women due to breast cancer. There is no way we can prevent breast cancer, but we can definitely detect it early and treat adequately. There is need for simple biochemical investigations which can be easily assayed and are less expensive. Materials and Methods: The present cross-sectional analytical study was conducted in department of biochemistry in collaboration with surgery department. Total of 200 subjects of 25-75 age group were included in the study out of which 100 were cases of breast cancer and 100 age and sex matched healthy controls. Serum levels of LDH were estimated in all subjects. Result: The present study shows that there was statistically significant increase in serum LDH in cases compared to controls. Conclusion: Serum LDH levels were found to be higher in breast cancer cases than controls which may serve as biomarker in carcinoma breast. It may help in assessing progression of the disease. It can be easily assayed in laboratories.

Key Word: Carcinoma of breast, Lactate dehydrogenase

 

 

 

INTRODUCTION

Carcinoma breast is commonest cancer in urban and rural females in India^{1, 2.} With over one million new cases in the world each year, breast cancer is the commonest malignancy in women (23% of all the cancers), ranking second overall when both sexes are considered together³. Cancer is a group of diseases that cause cells in the body to change and grow out of control. Breast cancers begin in the parts of the breast tissue that are made up of glands for milk production, called lobules, and ducts that connect the lobules to the nipple. It is a clonal disease. A malignant proliferation of epithelial cells lining the ducts or lobules of breast occurs in breast cancer. The rate of rise of breast cancer in developing nation like India is so rampant. If we do not act now, we will be in a major shock in the next twenty years. In India, around 1, 55,000 new cases were diagnosed with the breast cancer, burden in India has almost reached about 2/3rds of that of the US and is steadily rising. For the years 2015, around 76000 deaths are reported⁴. The mean age of occurrence is about 42 in India as compared to 53 in white women. While considering the strategy of treatment, accurate estimation of prognosis in breast cancer is very important. Breast cancer has a long and variable clinical course. It started with primary breast cancer and complicated by its secondary spread to regional lymph nodes, followed by metastasis to distant organs e.g. soft tissues, bones, etc. Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. It catalyzes the conversion of lactate to pyruvic acid. LDH is involved in tumor initiation and metabolism. Cancer cells rely on increased glycolysis resulting in increased lactate production in addition to aerobic respiration in the mitochondria, even under oxygen-sufficient conditions a process known as the Warburg effect⁵. This mechanism allows tumorous cells to convert the majority of their glucose stores into lactate regardless of oxygen availability. For this reason, LDH and the possibility of inhibiting its activity has been identified as a promising target in cancer treatments focused on preventing carcinogenic cells from proliferating. While recent studies have shown that LDH activity can act as a general marker in the prognosis of cancers. Diagnosis at advanced stages of disease contributes to the high mortality rate among women due to breast cancer, which can be attributed to low levels of awareness, cumbersome referral pathways to diagnosis, limited access to effective treatment at regional cancer centers and incomplete treatment regimens.^{6,7,8,9,10,11.} There is no way we can prevent breast cancer, but we can definitely detect it early and treat adequately. Only and only with early detection, we can achieve a longer survival. Several tumor markers are available these days.

 

AIMS AND OBJECTIVES

The analytical methods of many of these are unapproachable for general population as facilities for these are available only at sophisticated and well equipped centers with latest technology and are expensive. There is therefore need for simple biochemical investigations which can be easily assayed and are less expensive¹². So making use of some simple, easily available and easy to assessserum biochemical parameters may prove beneficial for diagnosis or assessing prognosis in cancer patients. In view of that present study is carried out

1. To study serum levels of lactate dehydrogenase in cases of breast cancer and normal healthy age and sex matched controls.

2. To evaluate whether the serum levels of lactate dehydrogenase are significantly higher in cases of breast cancer as compared to controls.

 

 

MATERIALS and METHODS

1. Study design: Cross sectional analytical study.

2. Study period: May 2015 to October 2016.

3. Study place: Department of Biochemistry and Surgery, Tertiary Care Hospital.

4. Sample size determination: a total of 200 subjects were included in the present study. Sample size was calculated by using MedCalc Statistical Software.¹³

5. Study population: The study consisted of 2 groups of 100 subjects each between 25-75 years of age as follows:

1. 100 cases of breast cancer.                                    

2. 100 Age and sex matched healthy controls.

The study protocol was approved by the Institutional Ethical Committee.

Inclusion Criteria

Cases: Criteria for breast cancer patients:

Histopathologically confirmed female patients of carcinoma breast, of stage I, II and III, IV between 25-75 years of age.                

Controls: Criteria for controls: Age and sex matched healthy females without family H/O carcinoma
breast.

Exclusion Criteria

Cases and controls:                                                                        

1) Patients with benign breast disease.

2) Patients with history of renal impairment in the past or having been diagnosed currently to have some kidney diseases like PCKD, glomerulonephritis, renal failure.

3) Patients with history of hepatic impairment in the past or having been diagnosed currently to have liver disease like cirrhosis, hepatitis.                         

4) Patients with anemia (Hb<10 gm %)

5) Patients having mass or carcinoma anywhere else in the body.                            

6) Patients with – Myocardial infarction, pancreatic disease, Diabetes mellitus.

 Collection of blood: 5mL of venous blood was collected in plain bulb from median cubital vein with all aseptic precautions after obtaining informed consent from all the study subjects. Hemolysed samples were excluded from the study .Samples were analysed immediately.

Equipments for analysis: TRANSASIA ERBA ChemPlusSemi Automatic Analyzer and Serum LDH was estimated using modified IFCC method.

RESULTS

The present study was conducted in the department of Biochemistry, of a tertiary care medical institute. The period of study was from May 2015 to October 2016.         
Study Design: Cross sectional comparative study A total of 200 subjects were enrolled in this study, who were further divided into two groups of 100 subjects, each between 25-75 years of age as histopathologically confirmed breast cancer cases and age, weight matched controls. Data was analyzed using unpaired t test. P< 0.05 was considered to be statistically significant and P< 0.001 was taken as statistically highly significant.

 

Table 1: Age distribution of study subjects

Age distribution of study subjects shows that the mean age was 38.23±9.54 for controls and 40.21 ± 10. 24 for cases. (Table1)

 

Table 2: Comparison of mean of lactate dehydrogenase in study groups (unpaired t test).

 

Graph 1: Comparison of mean of LDH in the study group.

Comparison of the mean of LDH in the study groups show that the mean of LDH in controls and cases were 269.37±65.6 IU/L 616.55±109.04 IU/L respectively. On comparison in the two groups using unpaired t test, was found statistically highly significant with P value <0.001

DISCUSSION

Breast cancer is one of the commonest causes of cancer mortality in females. It is responsible for the death of millions of women worldwide every year. It is so widespread that it has become a genuine problem for public health. India is experiencing rapidly increasing cancer incidences that carry many challenges that are distinctive of developing countries. Human breast carcinoma is a clonal disease in which a single transformed cell which is a product of a series of somatic or germ line mutations, eventually expresses its full malignant potential. It is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast. It is a disease which usually begins as a localized proliferation of cells, which over the course of time, spreads to regional lymph nodes and then to distant tissues in the body (bones, liver, lungs, etc.). Earlier studies focused onalteration in serum levelsLDH^14,23 have found association of alteration in serum levels of LDH. Many studies have tried to evaluate role of tumor markers in diagnosis of carcinoma of breast. In view of this present study was undertaken to study serum levels of Lactate dehydrogenase in cases of breast cancer and normal controls to evaluate serum levels of lactate dehydrogenase are significantly higher in cases of breast cancer compared to normal controls and to find out it’s assessment in the prognosis of breast carcinoma. During our present study one group consisting of histopathologically confirmed 100 cases of breast cancer and another group which contain healthy age matched controls were taken into consideration. The relevance of recorded alterations in the status of serum LDH during the course of present study is presented as follows. The present study shows that there was statistically significant increase in serum LDH in cases compared to controls. This finding is in accordance with findings reported by Guddanti R et al¹⁴, Kaur A et al ¹⁶, Jarari A et al ¹⁸ in which they suggested Serum LDH is the consequence of the disruption of the cell membrane of a large fraction of dividing malignant cells whose metabolic hallmark is anaerobic glycolysis, because of increased LDH enzyme activity increased levels of lactic acid found. This increase in serum LDH levels could be responsible for excretion of large amount of lactic acid by the tumour cells consequent upon the anaerobic glycolytic pathway operating in tumour cells when compared to normal cells. Present study shows the mean of LDH in controls and cases were 269.37±65.6 IU/L 616.55±109.04 IU/L respectively with statistically highly significant with P value <0.001 which suggest an immense potential of LDH as a marker for breast cancer. So this enzyme may therefore be serve as supportive biochemical marker along with clinical and histopathological findings in cases of patients with suspicious diagnosis.

 

CONCLUSION

The present study shows serum LDH levels higher in breast cancer cases than controls. High serum LDH levels may warrant an intervention that could be initiated at an earlier stage of the disease. Monitoring of serum LDH levels can be used as a prognostic indicator in patients with breast cancer. Serial measurement of this enzyme will have a prognostic significance and may help in treatment decisions. Serum LDH is less expensive and can be easily assayed. Advantage of this parameter is that it is simple, accurate, cost effective and can be assayed in smaller laboratories which do not have sophisticated technologies. So serum LDH can be used as biomarker in all suspected carcinoma breast patients as a routine screening test.

 

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