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ORIGINAL ARTICLE
Year : 2016  |  Volume : 29  |  Issue : 2  |  Page : 337-340

Evaluation of interleukin-6 and C-reactive protein in patients with breast cancer at Menoufia University Hospitals


Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission22-Feb-2015
Date of Acceptance16-Apr-2015
Date of Web Publication18-Oct-2016

Correspondence Address:
Mona T Ahmed El-Gendy
Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Gamal Abdel Nasser Street, Shebin Al-Kom, Al-Menoufia, 32511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.192447

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  Abstract 

Objectives:
The aim of this study was to determine the serum level of interleukin-6 (IL-6) and C-reactive protein (CRP) in patients with breast cancer and to correlate them with the staging of the disease.
Background:
Breast cancer is a disease that continues to plague women. IL-6 and CRP are found to be elevated in various inflammatory and malignant diseases, and their levels are found to correlate with the extent of the disease.
Patients and methods:
A total of 39 female patients with breast cancer were identified for the study. Serum level of IL-6 was assessed with enzyme-linked immunosorbent assay, and CRP was measured by means of immunoturbidimetry. The patients were classified into six groups on the basis of the pathological Tumor-Node-Metastasis (TNM) system. Statistical analyses of the data were then processed.
Results:
Increase in cancer invasion and staging are generally associated with increase in preoperative serum IL-6 and CRP level. IL-6 and CRP level correlate with lymph node metastasis (P > 0.001) and distant metastasis (P > 0.001). Serum IL-6 and CRP level correlate with TNM staging (P > 0.001).
Conclusion:
The levels of IL-6 and CRP have a positive correlation with the TNM staging system of breast cancer. Hence, IL-6 and CRP could be used as parameters to assess the prognosis of breast cancer patients.

Keywords: breast cancer, C-reactive protein, interleukin-6


How to cite this article:
El Saeed GK, Hosny Abou-elela DM, Ahmed El-Gendy MT. Evaluation of interleukin-6 and C-reactive protein in patients with breast cancer at Menoufia University Hospitals. Menoufia Med J 2016;29:337-40

How to cite this URL:
El Saeed GK, Hosny Abou-elela DM, Ahmed El-Gendy MT. Evaluation of interleukin-6 and C-reactive protein in patients with breast cancer at Menoufia University Hospitals. Menoufia Med J [serial online] 2016 [cited 2019 Nov 21];29:337-40. Available from: http://www.mmj.eg.net/text.asp?2016/29/2/337/192447


  Introduction Top


Breast cancer is a disease affecting millions of women, as well as men, all over the world. The Tumor-Node-Metastasis (TNM) system of classification is used for staging of the disease, which has a strong influence on the prognosis of the patient [1]. Interleukin-6 (IL-6) is a typical pleiotropic cytokine that modulates a variety of physiological differentiation, survival, and apoptosis [2]. IL-6 has a role in cancer; IL-6 regulates chronic inflammation, which can create a cellular microenvironment beneficial to cancer growth [3].

IL-6 is also a growth factor for lymphatic, renal, bladder, and colorectal cancer cells [4] and is involved in the control of cell proliferation and apoptosis [5]. Despite the large number of publications, the epidemiologic role of IL-6 in cancer remains unclear [6].

C-reactive protein (CRP) is one of the plasma proteins known as acute-phase protein, whose plasma concentration increase (or decrease) by 25% or more during inflammatory disorder. CRP can rise to as high as 1000-fold with inflammation. Conditions that commonly lead to marked change in CRP include infection, trauma, surgery, burns, inflammatory conditions, and cancer. Moderate changes occur after strenuous exercise, heat stroke, and childbirth. Small changes occur after physical stress and in several psychiatric illnesses [7].

CRP is therefore a test of value in medicine reflecting the presence and the intensity of inflammation, although an elevation in CRP is not the diagnostic sign of any one condition [8].

In contrast, CRP is probably the single most commonly used laboratory test for the early diagnosis of neonatal sepsis. It is, however, well known that the CRP concentration does not increase very early during an infection and a low value does not rule out sepsis. The production of CRP does not start until 6 h after the onset of the infection [9].


  Patients and Methods Top


The present study was carried out at the Department of Clinical Pathology, Faculty of Medicine, Menoufia University, between December 2012 and December 2014.

Patients without neoadjuvant chemotherapy were selected from the surgery outpatient clinic in Menoufia University Hospital.

This study included 39 female patients with breast cancer, and their ages ranged from 21 to 80 years. Diagnosis was made on the basis of clinical, radiological, and histopathological examination. In addition, 12 apparently healthy age-matched and sex-matched individuals were involved in this study as a control group.

The patients were classified into six groups on the basis of the pathological TNM staging system:

  1. Primary tumor (T1 = 2 cm, T2 = 2–5 cm, T3 = >5 cm, T4 = chest wall or skin infiltration).
  2. Nodal stage (N1 = 1–3 nodes, N2 = 4–9 nodes, N3 = >10 nodes).
  3. Absence (M0) or presence (M1) of metastasis.


Group I included three patients with T2 N0 M0 (stage IIa).

Group II included 10 patients with T2 N1 M0 (stage IIb).

Group III included seven patients with T3 N1 M0 and T2 N2 M0 (stage IIIa).

Group IV included eight patients with T4 N1 M0 and T4 N2 M0 (stage IIIb).

Group V included six patients with T3 N3 M0 and T2 N3 M0 (stage IIIc)

Group VI included five patients with T3 N1 M1, T2 N2 M1, and T3 N4 M1 (stage IV).

All patients were subjected to the following:

  1. Full history taking and clinical examination.
  2. Radiological investigation including mammography with complementary ultrasound, chest radiography, abdominal ultrasound, and bone scan.
  3. Routine laboratory investigation including liver and renal function tests, complete blood picture, and routine breast tumor markers including estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2.
  4. Blood sample investigation for IL-6 and CRP level on admission.


IL-6 was evaluated with Orgenium Laboratories' Koivu-Mankkaan tie 6 B, 02101 Espoo, Finland human IL-6 enzyme-linked immunosorbent assay kit. It is an in-vitro enzyme-linked immunosorbent assay for the quantitative measurement of human IL-6 in serum, plasma, cell culture supernatants, and urine. The assay uses an antibody specific for human IL-6 [0].

The normal value of IL-6 in the serum is less than 7 pg/ml [0].

CRP was measured with the Orion Diagnostica Turbox assay for CRP. It is a liquid-phase, immunoprecipitation assay with nephelometric endpoint detection. The resulting light scattering is directly proportional to CRP concentration in the sample [1].

The normal value in human serum is less than 5 mg/l [1].

The results were tabulated and statistically analyzed using SPSS (Statistical Package SPSS) version 17.0 SPSS Inc., Chicago, IL on IBM compatible computer.


  Results Top


In this study the mean age of the control group was 44.5, whereas the mean age of the study group was 51.95, which was not statistically significant.

Moreover, in the present study, there was significant relation between the study group and the control group as regards CRP (P<0.05), and there was a highly significant relation between them as regards IL-6 (P < 0.01).

In this study, the median level of IL-6 increased proportionally with the stage of the cancer. The median level of IL-6 was 8.0–4.44 pg/ml in stage IIa, 11.45 ± 5.14 pg/ml in stage IIb, 16.57 ± 4.64 pg/ml in stage IIIa, 20.25 ± 2.7 pg/ml in stage IIIb, 27.08 ± 3.67 pg/ml in stage IIIc, and 38.2 ± 4.82 pg/ml in stage IV; this difference was statistically significant (P<0.001).

In addition, serum IL-6 levels were significantly higher in patients with distant metastasis (38.2 ± 4.82 pg/ml) compared with those without distant metastasis (18.15 ± 6.63 pg/ml); the difference was also statistically significant (P<0.001).

In this study, we also noted significant differences in the CRP level in cancer stage. The median level of CRP was 7.0 ± 0.0 mg/dl in stage IIa, 6.5 ± 2.07 mg/dl in stage IIb, 7.43 ± 3.60 mg/dl in stage IIIa, 5.5 ± 2.45 mg/dl in stage IIIb, 17.33 ± 7.17 mg/dl in stage IIIc, and 36.4 ± 13.57 in stage IV (P<0.001).

Moreover, there was a significant increase in the level of CRP in patients with distant metastasis (36.4 ± 13.57) compared with patient without distant metastasis (8.41 ± 5.53).

There was a high significant progressive increase in the mean value of serum IL-6 and CRP from group I to group V in breast cancer patients.


  Discussion Top


In this study, the median level of IL-6 increased proportionally with the stage of the cancer. The median level of IL-6 was 8.0–4.44 pg/ml in stage IIa, 11.45 ± 5.14 pg/ml in stage IIb, 16.57 ± 4.64 pg/ml in stage IIIa, 20.25 ± 2.7 pg/ml in stage IIIb, 27.08 ± 3.67 pg/ml in stage IIIc, and 38.2 ± 4.82 pg/ml in stage IV; this difference was statistically significant (P<0.001).

The result of this study was in agreement with that of Ravishankatan and Karunanithi [2], who found that the serum levels of both IL-6 and CRP were statistically significant and related to the stage of breast cancer.

Pierce et al. [3] performed their study on 202 breast cancer patients and reported that IL-6 level increases as the aggrieve behavior of tumor increases (IL-6 level increase as the stage of cancer increase).

In this study, we also noted significant differences in the CRP level in cancer stage. The median level of CRP was 7.0 ± 0.0 mg/dl in stage IIa, 6.5 ± 2.07 mg/dl in stage IIb, 7.43 ± 3.60 mg/dl in stage IIIa, 5.5 ± 2.45 mg/dl in stage IIIb, 17.33 ± 7.17 mg/dl in stage IIIc, and 36.4 ± 13.57 in stage IV (P<0.001).

These results were in agreement with those of Isabel et al. [4], who found that elevated CRP is linked to poor prognosis and aggressiveness of the breast cancer tumor and therefore represents a consequence of established prognostic factors, such as tumor size and grade. Moreover, this study result was in agreement with that of Touvier et al. [5], who found that higher levels of CRP were also associated with poor clinicopathological features (such as number of metastases and response to chemoendocrine therapy) and poorer overall survival in a prognostic study of metastatic breast cancer ([Table 1],[Table 2],[Table 3],[Table 4]).
Table 1: Statistical comparison between cases and controls as regards C-reactive protein and interleukin-6

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Table 2: Statistical relationship between TNM classification and C-reactive protein

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Table 3: Statistical relationship between TNM classification and interleukin-6

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Table 4: Statistical comparison between different tumor stages as regards C-reactive protein and interleukin-6

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Conflicts of interest

There are no conflicts of interest.[15]

 
  References Top

1.
Ravishankaran P, Karunanithi R. Clinical significance of preoperative serum IL6 and CRP level in breast cancer patients. World J Surg Oncol 2011; 9:18.  Back to cited text no. 1
    
2.
Kamimura D Ishihara K, Hirano T. IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev Physiol Biochem Pharmacol 2003; 149:1–38.  Back to cited text no. 2
    
3.
Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res 2006; 4:221–233.  Back to cited text no. 3
    
4.
Aggarwal BB, Shishodia S, Sandur SK, Pandey MK, Sethi G. Inflammation and cancer: how hot is the link?. Biochem Pharmacol 2006; 72:1605–1621.  Back to cited text no. 4
    
5.
Calo V, Migliavacca M, Bazan V, Macaluso M, Buscemi M, Gebbia N, Russo A. STAT proteins: from normal control of cellular events to tumorigenesis. J Cell Physiol 2003; 197:157–168.  Back to cited text no. 5
    
6.
Heikkila K, Ebrahim S, Lawlor DA. Systemic review of the association between circulating interleukin-6 (DL-6) and cancer. Eur J Cancer 2008; 44:937–945.  Back to cited text no. 6
    
7.
Ridker PM, Libby P. Risk Factors for Atherothrombotic Disease. In: Libby P, Bonow RO, Mann DL, Zipes DP, editors. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 8th ed. Ch. 39. Philadelphia, PA; Saunders Elsevier; 2007.  Back to cited text no. 7
    
8.
Pop-Busui R, Kirkwood I, Schmid H, Marinescu V, Schroeder J, Larkin D, et al. Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction. J Am Coll Cardiol. 2004; 44:2368-2374.  Back to cited text no. 8
    
9.
Bassuoni MA, Helwa MA, Mona MAD. Neutrophil expression of CD46 in the diagnosis of early onset neonatal sepsis. Menoufia Med J 2014; 27:284–289.  Back to cited text no. 9
  Medknow Journal  
10.
Croce MA, Fabian TC, Patton JH Jr, Melton SM, Moore M, Trenthem LL. Partial liquid ventilation decreases the inflammatory response in the alveolar environment of trauma patients. J Trauma 1998; 45:273–282.  Back to cited text no. 10
    
11.
Peltola H, Saarinen UM, Siimes MA. C-reactive protein in rapid diagnosis and follow-up of bacterial septicemia in children with leukemia. Pediatr Infect Dis 1983; 2:370–373.  Back to cited text no. 11
    
12.
Ravishankatan P, Karunanithi R. Clinical significance of preoperative serum interleukin-6 and C-reactive protein level in breast cancer patients. World J Surg Oncol 2011; 9:18.  Back to cited text no. 12
    
13.
Pierce BL, Ballard-Barbash R, Bernstein L, Baumgartner RN, Neuhouser ML, Wener MH, et al. Elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients. J Clin Oncol 2009; 27:3437–3444.  Back to cited text no. 13
    
14.
Sicking I, Edlund K, Wesbuer E, Weyer V, Battista MJ, Lebrecht A, et al. Prognostic influence of pre-operative C-reactive protein in node-negative breast cancer patients. PLoS One 2014; 9:e111306.   Back to cited text no. 14
    
15.
Touvier M, Fezeu L, Ahluwalia N, Julia C, Charnaux N, Sutton A, et al. Association between prediagnostic biomarkers of inflammation and endothelial function and cancer risk: a nested case–control study. Am J Epidemiol 2013; 177:3–13.  Back to cited text no. 15
    



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



 

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