|Year : 2018 | Volume
| Issue : 1 | Page : 10-13
Evaluation of Serum IgA level in nontreated and treated oral squamous cell carcinoma patients
Richa Mishra1, Thimmarasa V Bhovi1, Prashant P Jaju1, Manas Gupta1, Kriti Shrivastava1, Ritu Mishra2
1 Department of Oral Medicine and Radiology, Rishiraj College of Dental Science and Research Center, Bhopal, Madhya Pradesh, India
2 Department of 1Oral Pathology and Microbiology, Rishiraj College of Dental Science and Research Center, Bhopal, Madhya Pradesh, India
|Date of Submission||13-Nov-2017|
|Date of Acceptance||17-Feb-2018|
|Date of Web Publication||23-Apr-2018|
Dr. Richa Mishra
Department of Oral Medicine and Radiology, Rishiraj College of Dental Science and Research Center, Gandhi Nagar, Bhopal - 462 036, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Research in early cancer detection has led to discovery of many immunological tumor markers that contribute considerably to supplement the method of diagnosis. High serum immunoglobulin A (IgA) values in patients with cancer have been used as tumor markers. Aims and Objectives: To evaluate and compare the serum IgA levels in nontreated, treated oral squamous cell carcinoma (SCC) patients, and control group. Materials and Methods: A total of 60 patients were included in the study. 20 biopsy confirmed oral SCC patients, who have received no medical treatment, 20 oral SCC patients treated with surgery and/or radiotherapy and 20 normal healthy individuals. Venous blood samples were collected from anterior cubital vein and were delivered to the biochemistry laboratory for the estimation of serum IgA level by nephelometry method. Statistical Analysis Used: Statistical method employed were the Pearson's Chi-square test and One-way analysis of variance (Welch) followed by Games-Howell post-hoc test. Results: We observed significant difference for serum IgA between study subjects in control, nontreated and treated oral SCC patients (P < 0.001). Serum IgA level in nontreated group was significantly higher than treated group and there was an approximately two-fold increase in serum IgA level in nontreated oral SCC patients when compared to that of the normal healthy individuals. Conclusion: Serum level of IgA might be employed as diagnostic and prognostic indicators in oral cancer.
Keywords: Oral squamous cell carcinoma, serum IgA, serum immunoglobulins
|How to cite this article:|
Mishra R, Bhovi TV, Jaju PP, Gupta M, Shrivastava K, Mishra R. Evaluation of Serum IgA level in nontreated and treated oral squamous cell carcinoma patients. J Indian Acad Oral Med Radiol 2018;30:10-3
|How to cite this URL:|
Mishra R, Bhovi TV, Jaju PP, Gupta M, Shrivastava K, Mishra R. Evaluation of Serum IgA level in nontreated and treated oral squamous cell carcinoma patients. J Indian Acad Oral Med Radiol [serial online] 2018 [cited 2019 May 22];30:10-3. Available from: http://www.jiaomr.in/text.asp?2018/30/1/10/230881
| Introduction|| |
Oral cancer is the 15th most prevalent cancer worldwide. Among the oral cancers, 90% of them are squamous cell carcinomas (SCC). Although there have been significant advances in surgery and radiation therapy, the 5-year survival of the patient has remained at about 52% for the past few decades.,
Research in early cancer detection has led to discovery of many immunological tumor markers that contribute considerably to supplement the established method of diagnosis. The term “tumor marker” is applied to indicate the risk of cancer and its future behavior. The different tumor markers for the study of human cancers include oncofetal proteins, enzymes, hormones, polyamines, tumor associated antigens, circulating immune complexes (CIC), lipids, viral markers, immunoglobulin (Ig), and glycol proteins.
Igs are protein molecules produced by the terminal cells of B-cell differentiation known as “plasma cells” and are localized in the beta and gamma-globulin fractions of the serum. On the basis of differences in physicochemical properties and antigenic structure, five different Ig classes can be distinguished today, IgM, IgG, IgA, IgD, and IgE.,,
IgG is the predominant Ig in normal serum (70–75%, approximately 1000 mg/dL). IgA is the next most predominant Ig, accounting for approximately 15–20% (approximately 200 mg/dL).
Ig serves as a specific link between antigenic determinants on tumor cell and the host-effectors cells. Many authors have studied specific Ig response caused by cancer. Literature review reveals multifarious observations, with increased, decreased, and even normal levels of IgA. In addition, the severity of the immune derangements resulting from surgery, radiotherapy, or chemotherapy may be more important than pretherapy status in determining prognosis.,
Hence, this study was designed to quantitatively evaluate IgA in serum of oral SCC patients before and after the treatment, thereby to observe any possible association of this Ig in the pathogenesis of disease and for the prognosis of the disease.
| Materials and Methods|| |
This prospective study was conducted in Department of Oral Medicine and Radiology, Rishiraj College of Dental Science & Research Centre and Jawaharlal Nehru Cancer Hospital, Bhopal (M.P.), after obtaining institutional ethical committee clearance and informed written consent from the subjects. The patients having oral SCC reporting to the above centers were included in the study based on random selection.
A total of 60 patients with age range of 35–70 years were included in the study among these 20 were nontreated oral SCC patients, 20 were those who have undergone surgical and/or radiotherapy treatment, and 20 were normal healthy individuals. In all, extreme care was taken to selectively exclude the subjects having metastatic tumors in the oral cavity, patients with carcinoma of other parts of the body, control group with compromising systemic conditions and neoplastic disorders.
The data was obtained from those subjects satisfying the criteria and 5 mL of venous blood samples were collected from the anterior cubital vein in blood tubes. The blood was allowed to clot for 60 min and centrifuged at 2000 rpm for 10 min. The serum was separated and was delivered to the biochemistry laboratory for the estimation of serum IgA level by nephelometry method.
| Results|| |
Statistical analysis was done using Statistical Package for Social Sciences (SPSS) v. 21. Frequencies, percentages, mean, standard deviation (SD), and minimum and maximum values of variables were calculated. For categorical data [gender, diagnosis, tumor, node and metastasis (TNM) staging], Pearson's Chi-square test was applied for analysis. When expected frequency in any cell was less than 5, Chi-square test with Yates' correction was applied.
In our study, age range for all 60 subjects was 35–70 years with a mean age in control, nontreated and treated groups were 49.45 years, 48.10 years, and 49.35 years respectively. Mean and SDs of serum IgA in control, nontreated and treated groups were 302.65 ± 49.15 mg/dL, 642.80 ± 100.45 mg/dL, and 322.80 ± 76.03 mg/dL respectively. Minimum and maximum values of serum IgA in control group were 228.00 mg/dL and 387.00 mg/dL, in nontreated group were 390.00 mg/dL and 788.00 mg/dL and in treated group were 190.00 mg/dL and 434.00 mg/dL [Table 1] and [Figure 1]. There was a statistically significant difference for serum IgA between study subjects in control, nontreated and treated groups (P < 0.001). Serum IgA level in nontreated group was significantly higher than control group (mean difference = -340.15 mg/dL, P < 0.001). Serum IgA level in nontreated group was significantly higher than treated group (mean difference = 320.00 mg/dL, P < 0.001). There was no significant difference for serum IgA levels between control and treated groups (mean difference = -20.15 mg/dL, P > 0.05). Increased levels of mean IgA values were found among oral SCC patients when compared to control group [Table 2] and [Figure 2].
|Table 1: Comparison of serum immunoglobulin A (IgA) of study subjects in control, non-treated, and treated groups|
Click here to view
|Figure 1: Comparison of serum IgA of study subjects in control, non-treated and treated groups|
Click here to view
|Table 2: Pairwise comparison of serum immunoglobulin A (IgA) in control, nontreated, and treated groups using Games–Howell post-hoc test|
Click here to view
|Figure 2: Pairwise comparison of serum IgA in control, non-treated and treated groups using Games-Howell post-hoc test|
Click here to view
In the present study, nontreated and treated oral SCC patients were grouped in different stages following the American Joint Committee on Cancer (AJCC) TNM staging system as stage I, stage II, stage III, and stage IV. Serum levels of IgA was increased in the patients with oral SCC when compared to control group, which also correlated with clinical staging of the malignancies and treated group in all four clinical stages of oral SCC and the greatest rise of serum IgA was seen in stage IV patients [Table 3] and [Figure 3]. After 3 months of treatment, fall in serum IgA level was significant in all four stages of oral SCC but greatest fall in serum IgA level was seen in stage I and stage II patients. There was no significant difference for serum IgA levels between control and post treatment groups in these clinical stages [Table 3] and [Figure 3].
|Table 3: Comparison of serum immunoglobulin A (IgA) of study participants in control, nontreated, and treated groups for different stages according to tumour, node and metastasis (TNM)|
Click here to view
|Figure 3: Comparison of serum IgA of study subjects in control, non-treated and treated groups for different stages according to TNM|
Click here to view
| Discussion|| |
Oral cancer is a major health issue in different population and it is responsible for 3–10% of cancer mortality worldwide. The incidence of oral cancer is highest in India, South and Southeast Asian countries. In India, 90–95% of the oral cancer is SCC.,
Early detection of cancer is a continuing goal since decades. Thorough extraoral and intraoral examination of is a prerequisite. Aids to oral examination include vital staining–Toluidine Blue/Lugol's Iodine, VELscope, saliva-based oral cancer diagnostics, DNA Ploidy Quantification of nuclear DNA content, Tumor Markers, and many more. The prognosis of oral cancer has remained relatively unchanged for the past years despite these advances in diagnosis and management.
The tumor antigens can initiate the formation of humoral antibodies and/or elicit cell-mediated immune responses which causes the changes in the quantitative levels of Igs during and after oral cancer treatment.
The serum Igs have been assayed in various diseases. The regulation of serum Igs in human cancers has been reported by various workers such as carcinoma of cervix by Vasudevan et al. (1971), prostate cancer by Ghankari et al. (1993), and nasopharyngeal carcinoma by De-en et al. (1988).
In our study, mean and SDs of serum IgA in control, nontreated and treated groups were 302.65 ± 49.15 mg/dL, 642.80 ± 100.45 mg/dL, and 322.80 ± 76.03 mg/dL respectively. There was a statistically significant difference for serum IgA between study subjects in control, nontreated and treated groups (P < 0.001). Increased levels of mean IgA values were found among oral SCC patients when compared to control groups which may be due to enhancement of Ig synthesis induced by the solid tumor [Table 1] and [Figure 1]. It is also possible that IgA or some other Ig may in fact, be acting as an enhancing antibody. Similar observations were made by Schantz et al. (1988) where they demonstrated significant difference in only IgA titers between cancer patients and controls. Elevated IgA levels in cancer patients are reported by Scully (1982), Vijay Kumar et al. (1986), and recently Parveen et al. (2015). Increased IgA and IgG levels were observed in oral cancer by Brown et al. (1975), whereas Khanna et al. (1982) reported a significant increase in IgA as well as IgM levels, while these findings were contrary to the study done by Lasisi et al. (2013) where they showed that serum IgA concentration was lower in untreated orofacial carcinoma patients than in control group.
Another study was done in 1994 by Neuchrist et al. and in 2003 by De Souza et al. in which the serum concentrations of IgA for oral cancer patients and those for control subjects were similar while in our case serum IgA for oral cancer patients were elevated.
In present study, serum IgA concentration was decreased after the treatment of the oral SCC patients. This was in contrast to the results observed in a study conducted by De-en et al. in (1988) in which relationship of radiation therapy on immune system of oral cancer patients was observed and as a result they found that following radiation therapy, cell-mediated immunity was found to be lower than control but the Ig, CIC, and antinuclear antibody levels stayed at markedly higher levels.
We noticed increased IgA levels with the advancing stage of disease. These observations are consistent with the findings of Lorenz et al., Schantz et al., and Parveen et al. who reported the highest values of IgA in patients with advanced disease.
It is evident that in our study we have noticed a significant increase in serum Igs in patients with nontreated oral SCC when compared to those in the control group. The elevated levels correlated well with the extent of the malignant disease. Increased levels of Ig with advanced stage of cancer are indicative of an adverse prognosis.
| Conclusion|| |
Serum IgA would be a good prognostic indicator and can be considered as tumor markers. Increase in these tumor markers could be due to residual tumor, metastasis, recurrence, or subclinical disease. However, there is scope for further studies to investigate the prognostic efficiency of serum IgA and other serum Igs for oral cancer patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Shah FD, Begum R, Vajaria B, Patel KR, Patel JB, Shukla SN, et al
. A review on salivary genomics and proteomics biomarkers in oral cancer. Ind J Clin Biochem 2011;26:326-34.
Jane C, Nerurkar AV, Karjodkar FR. Circulating Immune complexes (CIC) as marker for disease progress in oral cancer. Indian J Clin Biochem 2007;22:114-7.
Parveen S, Taneja N, Bathi RJ, Deka AC. Evaluation of circulating immune complexes and serum immunoglobulins in oral cancer patients-a follow up study. Indian J Dent Res 2010;21:10-5.
] [Full text]
Loh RK, Vale S, McLean-Tooke A. Quantitative serum immunoglobulin tests. Aust Fam Physician 2013;42:195-8.
Zegers BJ, Stoop JW, Reerink-Brongers EE, Sander PC, Aalberse RC, Ballieux RE. Serum immunoglobulins in healthy children and adults. Levels of the five classes, expressed in international units per millilitre. Clin Chim Acta 1975;65:319-29.
Divya VC, Sathasivasubramanian S. Estimation of serum and salivary immunoglobulin G and immunoglobulin A in oral pre-cancer: A study in oral submucous fibrosis and oral lichen planus. J Nat Sci Biol Med 2014;5:90-4.
Epstein J, van der Waal I. Oral Cancer. In: Greenberg MS, Glick M, Ship JA, editors. Burket's Oral Medicine. 11th
ed. Hamilton: BC Decker Inc; 2008. p. 153-89.
Lasisi TJ, Yusuf BO, Lasisi OA, Akang E. Salivary and serum IgA evaluation of patients with oro-facial squamous cell carcinoma. Int J Otolaryngol Head Neck Surg 2013; 2:42-5.
Syamsundar B, Rao N, Faheem K. Epidemiological and clinicopathological study of oral cancer in a tertiary care hospital. Int J Med Res 2012;3:2376-80.
Rahman SS, Sarker MK, Khan MHA, Biswas SS, Saha MM. Clinical profile of oral squamous cell carcinoma patients attending a tertiary care hospital. Bang Med J Khulna 2014;47:3-6.
Mehrotra R, Gupta DK. Exciting new advances in oral cancer diagnosis: Avenues to early detection. Head Neck Oncol 2011; 3:1-8.
Vasudevan DM, Balakrishnan K, Talwar GP. Immunoglobulins in carcinoma cervix. Indian J Med Res 1971; 59:1653-59.
Ghankari DL, Goihar KS. An evaluation of serum and tissue bound immunoglobulins in prostatic disease. J Postgrad Med 1993;39:63-7.
Hu DE, Ling XS, Hu J, Li BL, Wang XF, Shen YG, et al
. The effects of radiotherapy on the immune system of patients with nasopharyngeal carcinoma. Br J Radiol 1988;61:305-8.
Schantz SP, Liu FJ, Taylor D, Beddingfield N, Weber RS. The relationship of circulating IgA to cellular immunity in head and neck cancer patients. Laryngoscope 1988;98:671-8.
Scully C. Immunological abnormalities in oral carcinoma and oral keratosis. J Maxillofacial Surg 1982;10:113-5.
Rajendran R, Sugathan CK, Remani P, Ankathil R, Vijayakumar T. Cell mediated and humoral immune responses in oral submucous fibrosis. Cancer 1986;58:2628-31.
Brown AM, Lally ET, Frankel A, Harwick R, Davis LW, Rominger CJ, et al
. The association of the IgA level of serum and whole saliva with the progression of oral cancer. Cancer 1975;35:1154-62.
Khanna NN, Das SN, Khanna S. Serum immunoglobulins in squamous cell carcinoma of the oral cavity. J Surg Oncol 1982;20:46-8.
Neuchrist C, Kornfehl J, Grasl M, Lassmann H, Kraft D, Ehrenberger K, et al
. Distribution of immunoglobulins in squamous cell carcinoma of the head and neck. Int Arch Allergy Immunol 1994;104:97-100.
de Souza RM, Lehn CN, Denardin OV. Serum and salivary immunoglobulin A levels in patients with cancer of the mouth and oropharynx. Rev Assoc Med Bras 2003;49:40-4.
Lorenz KJ, Süsal C, Opelz G, Maier H. Relationship between progression of disease and immunoglobulin A-anti-Fab-/F(ab')2 autoantibodies in patients with head and neck cancer. Otolaryngol Head Neck Surg 1998;118:130-6.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]