Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
Users Online: 210
Home | About us | Editorial board | Search | Ahead of print | Current issue | Archives | Submit article | Instructions | Subscribe | Contacts | Advertise | Login 

Table of Contents
Year : 2017  |  Volume : 11  |  Issue : 1  |  Page : 22-26

Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status of breast cancers in women visiting the Jos University Teaching Hospital

1 Department of Histopathology, Jos University Teaching Hospital, Jos, Nigeria
2 Department of Histopathology, Kaduna State University, Kaduna, Nigeria

Date of Web Publication15-Feb-2018

Correspondence Address:
Innocent Emmanuel
Department of Histopathology, Jos University Teaching Hospital, Jos
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/anm.anm_6_17

Rights and Permissions

Introduction: Breast cancer remains the most common malignancy in women and the leading cause of morbidity and mortality in this gender. The disease in the indigenous African woman is associated with an inherent aggressive biology and worst clinical outcome. As the malignancy is a heterogeneous entity, each case must be individually categorized for efficient therapy. Current clinical practice employs the use of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), as biomarkers to appropriately select patients that would benefit from targeted therapy against these major molecular pathways of the disease. This study aims at establishing the ER, PR, and HER2 status of breast cancer in women visiting the Jos University Teaching Hospital.
Materials and Methods: All histologically confirmed cases of breast cancer at the Jos University Teaching Hospital, between January 1, 2010, and December 31, 2012, with sufficient clinical records, were subjected to immunohistochemistry for the ER, PR, and HER2 status.
Results: A total of 96 cases of female breast cancers were histologically diagnosed during the period of the study. Sixty-three (65.6%) cases met the inclusion criteria. The predominant histological type was invasive carcinoma (no special type) accounting for 54 (85.7%) cases. Scarf Bloom Richardson Grade 1, 2, and 3 for the cancer cases were: 18 (28.6%), 29 (46.0%), and 16 (25.4%), respectively. The rate of ER, PR, and HER2 positivity were 36.5%, 28.6%, and 33.3%, respectively. There were 26 (41.3%) triple-negative cases.
Conclusion: The study shows a relatively low rate of hormone-receptor positivity, and higher HER2 positivity of breast cancers in our locality, which may be responsible for poor prognosis in our patients.

Keywords: Breast, cancer, estrogen, human epidermal growth factor receptor 2, Jos, progesterone, receptor

How to cite this article:
Emmanuel I, Mandong BM, Kwaghe BV, Yakubu D. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status of breast cancers in women visiting the Jos University Teaching Hospital. Ann Nigerian Med 2017;11:22-6

How to cite this URL:
Emmanuel I, Mandong BM, Kwaghe BV, Yakubu D. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 status of breast cancers in women visiting the Jos University Teaching Hospital. Ann Nigerian Med [serial online] 2017 [cited 2021 May 11];11:22-6. Available from: https://www.anmjournal.com/text.asp?2017/11/1/22/225612

   Introduction Top

Breast cancer remains the most common malignancy in women globally.[1],[2],[3],[4],[5],[6],[7],[8] In Jos (Nigeria), it is followed closely by cancers of the cervix, prostate, Non-Hodgkin's lymphoma, liver, and colorectum, respectively, for all cancers in both males and female.[9]

The breast cancer burden is increasing in developing countries. It is estimated that 70% of new cancer cases will occur in inhabitants of developing countries by the year 2020, and a vast number of these cancers occurring in females, would be of the breast.[10],[11],[12]

More disturbing about the management of breast cancer is the issue of late presentation in the African population and black American women.[5],[13],[14],[15],[16]

Breast cancer does present as a systemic disease from the onset, with some patients with early breast cancer developing metastases whatever the treatment undertaken.[17] Moreover, the intensity of local treatment does not correlate with survival and the risk of metastatic recurrence.[18] A possible explanation for this is blood-borne micro-metastases that are present at the time of initial diagnosis. These observations lead to a more conservative approach to surgical intervention in breast cancer and the concurrent use of medical therapy.[18] Since breast cancer, is a disease with significant clinical diversity, an individualized approach to management and treatment decision is necessary.[19],[20] In concurrent clinical practice, breast cancer biomarkers including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are routinely assessed to help select patients who are appropriate candidates for treatment that target these major molecular pathways of the disease.[20],[21],[22],[23],[24],[25],[26],[27],[28]

The purpose of this study was to establish the hormone receptors, and HER2 status of female breast cancers seen at our centre between January 2010 and December 2012, and to relate this finding with the age, histological type, and grade of the malignancy.

   Materials and Methods Top

Sixty-three cases of histologically confirmed breast cancers with complete bio-data were retrieved from the records of the diagnosis register of the Department of Histopathology, Jos University Teaching Hospital. This covered the period between January 1, 2010, and December 31, 2012.

All cases with sufficient bio-data were included while those with unsuitable tissue blocks were excluded from the study.

Histologically, confirmed breast cancers were subtyped and graded using the modified Bloom-Richardson system.[29],[30]

These cases were subjected to immunohistochemistry with immune-peroxidase (Avidin-Biotin complex technique) staining for estrogen, progesterone, and HER2 receptors. The antibody clone for ER, PR, and HER2 used were (dilution 1:100): NCL-L-ER; L-PGR; and NCL-L-CB11, respectively, all from Leica.

Paraffin-embedded tissue was cut at 3 microns thick and allowed to cool on a hot plate for an hour. Sections were taken into various stages of processing which included: water, xylene, alcohol, and finally water. Antigen retrieval was performed using citric acid solution (PH 6.0) in a microwave at power 100 for 15 min.

Sections were equilibrated by gently displacing the hot citric acid with running tap water for 3 min. Peroxidase was blocked in tissue using peroxidase block for 15 min. Sections were washed for 2 min with phosphate-buffered saline (PBS) mixed with Tween 20. Sections were then blocked with protein block for 15 min. Sections were washed for 2 min with PBS. Sections were incubated with primary antibody for 45 min. Sections were washed for 5 min with PBS. Secondary antibody was added for 15 min. Sections were washed twice with PBS. Polymer was added for 15 min. Sections were washed twice with PBS and diaminobenzidine (DAB) (diluted 1/100 with DAB substrate) for 5 min.

Sections were washed with water and counterstained for 2 min with hematoxylin. Sections were washed, dehydrated, cleared, and mounted.

The LEICA DM 500 (LEICA ICC500 HD) microscope was used to review the histological slides and acquire photomicrographs [Figure 1].
Figure 1: Photomicrographs of grade 2 breast cancer staining positively with H/E, ER, PR, and HER2 stains Section shows sheets of malignant epithelial cells exhibiting (a) marked pleomorphism, hyperchromasia, increased nucleocytoplasmic ratio, and occasional mitosis (H/E). (b and c) Strong nuclear staining for estrogen receptor antibody. (d and e) Strong nuclear staining for progesterone receptor antibody. (f and g) Intense and complete membrane staining for HER 2

Click here to view

The scoring system for ER and PR status was based on J score which scores the percentage of tumor cells with nuclear staining. Scores 0 was classified as negative; scores 1 and 2 as intermediate; and score 3 as positive.[31],[32]

HER2 staining was scored based on membrane staining pattern (intensity and completeness) - Hercept Test. 32 Score 0 and 1+ were classified as negative; Score 2+ as inconclusive (weakly positive); and score 3+ as positive.[32]

   Results Top

A total of 96 cases of breast cancers were diagnosed histologically at the Jos University Teaching Hospital during the period of the study. A total of 63 (65.6%) cases of these were included in this study, as they have adequate records and were sufficient for staining with the three immunomarkers.

The mean age at the diagnosis of breast cancers was 46.7 ± 11.1 years while the median age was 46 years. The age range was 28–74 years [Table 1].
Table 1: Age distribution of female patients diagnosed with breast cancer

Click here to view

The number of ER, PR, and HER2-positive cases were: 23 (36.5%), 18 (28.6%), and 21 (33.3%), respectively [Table 2] and [Table 3].
Table 2: Distribution of female breast cancer according to histological type, with respect to estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status

Click here to view
Table 3: Distribution of female breast cancer according to histological grade, with respect to estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status

Click here to view

The predominant histological type of breast cancers was invasive carcinoma no special type (NST) (54 cases) constituting 85.7% of cases. Of these, 18 (33.3%), 14 (25.9%), and 17 (32.7%) were positive for ER, PR, and HER2, respectively [Table 2].

The predominant histological grade was Grade 2 (29 cases) accounting for 46.0% of cases. Grades 1 and Grade 3 recorded 18 (28.6%) and 16 (25.4%) case, respectively.

   Discussion Top

The mean age realized in this study (46.7 years) is in conformity with an earlier study in our hospital, and many other African reports.[33],[34],[35],[36],[37],[38] This finding mirrors the earlier occurrence of breast cancer in Africans than in Caucasians, a fact attributed to a shorter life expectancy in the former than in the later.[7],[37],[38],[39] As fewer Africans attain an elderly age, only cancers occurring at an earlier age are seen.

Invasive carcinoma (NST) was the predominant histological subtype in our study. This finding has been corroborated by many reports across the world.[40],[41],[42],[43],[44]

A low rate of ER, and PR positivity was seen in this study. These lower representations for hormone-receptors positivity are consistent with a previous report from our center and other reports of African studies.[33],[45],[46],[47],[48] It follows, therefore, that fewer women in our locality and Africa would benefit from hormonal therapy employed against this disease.[27] This treatment option for hormone receptor-positive tumors involves blocking estrogen production with aromatase inhibitors (e.g., anastrazole), or blocking the action of estrogen on its receptor with receptor blocking agents (e.g., tamoxifen).[49]

The rate of positivity for human epidermal growth factor 2 in our study is consistent with values from earlier studies in Africa.[45],[46],[48],[50],[51] This is relatively higher than the rate of 12%–25% reported in Caucasians.[52],[53],[54],[55] Positivity for HER2 is predictive of favorable response to targeted therapy against HER2. This therapy against this receptor, either as adjuvant or neoadjuvant form is achieved using the monoclonal antibody trastuzumab (herceptin).[56] Trastuzumab targets HER2-positive breast cancers, inhibiting cell proliferation, and inducing cell death through various mechanisms, improving survival. More women in the African setting, therefore, are likely to benefit from this therapy relative to their Caucasian counterparts.

The proportional distribution between hormone receptor positivity and histological grade in this study showed that Grade 2 breast cancers have the highest percentage while Grades 1 and 3 have approximately equal number of cases. This finding is not in agreement with the decreasing pattern seen in studies from Algeria, and India, with Grade 1 having the highest percentage while Grade 3 the lowest.[57],[58],[59] As ER-positive tumors have been shown to have better prognosis, it is expected that most cases should be concentrated in Grade 1 (a mild histological grade). The discordant finding in this study could be attributed to small sample size.

   Conclusion Top

The study shows a relative low rate of hormone receptor, and higher rate of HER2-positive breast cancers in our locality, which may be responsible for poor prognosis in our patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, et al. The global burden of cancer 2013. JAMA Oncol 2015;1:505-27.  Back to cited text no. 1
Gudilla V. Knowledge and attitude towards breast cancer among women in Rombo district, Kilmanjaro region. Dar Es Salaam Med Stud J 2007;14:44-7.  Back to cited text no. 2
Celko AM. Breast cancer epidemiology in Czech Republic. Cent Eur J Public Health 1996;4:106-9.  Back to cited text no. 3
Saunders C, Vijay V, Stein J, Baum M. Setting up a breast cancer family history clinic. Ann R Coll Surg Engl 1999;81:393-8.  Back to cited text no. 4
Clegg-Lamptey J, Hodasi W. A study of breast cancer in Korle Bu Teaching Hospital: Assessing the impact of health education. Ghana Med J 2007;41:72-7.  Back to cited text no. 5
World Cancer Report. International Agency for Research on Cancer; 2008. Available from: http//www.globocan.jarcfr/factsheets/population/factsheet.asp?uno=900. [Last retrieved on 2015 Oct 02].  Back to cited text no. 6
Ohanaka CE, Ofoegbu RO. The pattern of surgical cancers in Nigeria: The Benin experience. Trop Doct 2002;32:38-9.  Back to cited text no. 7
Adebamowo CA, Ajayi OO. Breast cancer in Nigeria. West Afr J Med 2000;19:179-91.  Back to cited text no. 8
Mandong BM, Madaki KA, Manasseh AN. Malignant diseases in Jos: A follow up. Ann Afr Med 2003;2:49-53.  Back to cited text no. 9
Fregene A, Newman LA. Breast cancer in sub-Saharan Africa: How does it relate to breast cancer in African-American women? Cancer 2005;103:1540-50.  Back to cited text no. 10
Jones SB. Cancer in the developing world: A call to action. BMJ 1999;319:505-8.  Back to cited text no. 11
Kumar V, Abbas AK, Fausto N, editors. Pathologic Basis of Disease. 8th ed. Philadelphia: Saunders and Elsevier; 2010. p. 1065-96.  Back to cited text no. 12
Adesunkanmi AR, Lawal OO, Adelusola KA, Durosimi MA. The severity, outcome and challenges of breast cancer in Nigeria. Breast 2006;15:399-409.  Back to cited text no. 13
Brewster DH, Thomson CS, Hole DJ, Black RJ, Stroner PL, Gillis CR, et al. Relation between socioeconomic status and tumour stage in patients with breast, colorectal, ovarian, and lung cancer: Results from four national, population based studies. BMJ 2001;322:830-1.  Back to cited text no. 14
Vorobiof DA, Sitas F, Vorobiof G. Breast cancer incidence in South Africa. J Clin Oncol 2001;19:125S-127S.  Back to cited text no. 15
Oluwole SF, Fadiran OA, Odesanmi WO. Diseases of the breast in Nigeria. Br J Surg 1987;74:582-5.  Back to cited text no. 16
Christian MC, McCabe MS, Korn EL, Abrams JS, Kaplan RS, Friedman MA, et al. The national cancer institute audit of the national surgical adjuvant breast and bowel project protocol B-06. N Engl J Med 1995;333:1469-74.  Back to cited text no. 17
Ahmed MI, Lennard TW. Breast cancer: Role of neoadjuvant therapy. Int J Surg 2009;7:416-20.  Back to cited text no. 18
Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race, breast cancer subtypes, and survival in the Carolina breast cancer study. JAMA 2006;295:2492-502.  Back to cited text no. 19
Yaziji H, Taylor CR, Goldstein NS, Dabbs DJ, Hammond EH, Hewlett B, et al. Consensus recommendations on estrogen receptor testing in breast cancer by immunohistochemistry. Appl Immunohistochem Mol Morphol 2008;16:513-20.  Back to cited text no. 20
Allred DC, Carlson RW, Berry DA, Burstein HJ, Edge SB, Goldstein LJ, et al. NCCN task force report: Estrogen receptor and progesterone receptor testing in breast cancer by immunohistochemistry. J Natl Compr Canc Netw 2009;7 Suppl 6:S1-21.  Back to cited text no. 21
Walker RA. Immunohistochemical markers as predictive tools for breast cancer. J Clin Pathol 2008;61:689-96.  Back to cited text no. 22
Okobia MN, Bunker CH. Estrogen metabolism and breast cancer risk – A review. Afr J Reprod Health 2006;10:13-25.  Back to cited text no. 23
Osborne CK. Steroid hormone receptors in breast cancer management. Breast Cancer Res Treat 1998;51:227-38.  Back to cited text no. 24
Science daily. NOs Isn't Good for ER- Negative Breast Cancer Patients; 18 October, 2010. Available from: http://www.sciencedaily.com/release/2010/10/10/101018121356.htm. [Last retrieved on 2015 Oct 02].  Back to cited text no. 25
Mohsin SK, Weiss H, Havighurst T, Clark GM, Berardo M, Roanh le D, et al. Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: A validation study. Mod Pathol 2004;17:1545-54.  Back to cited text no. 26
Tamoxifen for early breast cancer: An overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet 1998;351:1451-67.  Back to cited text no. 27
Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN, et al. The HER-2 receptor and breast cancer: Ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 2009;14:320-68.  Back to cited text no. 28
Breast Cancer Grading. Scarf-Bloom-Richardson Grading. Ganfyd. Available from: http://www.ganfyd.org/index.php?title=breast_cancer_grading. [Last retrieved on 2015 Oct 02].  Back to cited text no. 29
Breast Cancer Grading at Lexington Med. CTR. The Elston Modification of the Scarff Bloom-Richardson System. Available from: http://www. Poptop.hypermart.net/brcagrd.html. [Last retrieved on 2015 Oct 02].  Back to cited text no. 30
ER/PR- Source Bioscience Healthcare. Available from: http://www.health.sourcebioscience.com/diagnostic-test/erpr. [Last retrieved on 2015 Oct 02].  Back to cited text no. 31
Immunohistochemistry. Cancer Quest. Available from: http://www.cancerquest.org.pathology-immunohistochemistry. [Last retrieved on 2015 Oct 02].  Back to cited text no. 32
Gukas ID, Jennings BA, Mandong BM, Igun GO, Girling AC, Manasseh AN, et al. Clinicopathological features and molecular markers of breast cancer in Jos, Nigeria. West Afr J Med 2005;24:209-13.  Back to cited text no. 33
Dauda AM, Misauno MA, Ojo EO. Histopathological types of breast cancer in Gombe, North Eastern Nigeria: A seven-year review. Afr J Reprod Health 2011;15:109-11.  Back to cited text no. 34
Ikpat OF, Ndoma-Egba R, Collan Y. Influence of age and prognosis of breast cancer in Nigeria. East Afr Med J 2002;79:651-7.  Back to cited text no. 35
Adebamowo CA, Adekunle OO. Case-controlled study of the epidemiological risk factors for breast cancer in Nigeria. Br J Surg 1999;86:665-8.  Back to cited text no. 36
Ijaduola TG, Smith EB. Pattern of breast cancer among White-American, African-American, and nonimmigrant West-African women. J Natl Med Assoc 1998;90:547-51.  Back to cited text no. 37
Rose DP, Royak-Schaler R. Tumor biology and prognosis in black breast cancer patients: A review. Cancer Detect Prev 2001;25:16-31.  Back to cited text no. 38
Anyanwu SN. Survival following treatment of primary breast cancer in Eastern Nigeria. East Afr Med J 2000;77:539-43.  Back to cited text no. 39
Thike AA, Iqbal J, Cheok PY, Chong AP, Tse GM, Tan B, et al. Triple negative breast cancer: Outcome correlation with immunohistochemical detection of basal markers. Am J Surg Pathol 2010;34:956-64.  Back to cited text no. 40
Ekanem VJ, Aligbe JU. Histopathological types of breast cancer in Nigerian women: A 12-year review (1993-2004). Afr J Reprod Health 2006;10:71-5.  Back to cited text no. 41
Abudu EK, Banjo AA, Izegbu MC, Agboola AO, Anunobi CC, Musa OA, et al. Malignant breast lessions at Olabisi Onabanjo University Teaching Hospital (O.O.U.T.H), Sagamu – A histopathological review. Niger Postgrad Med J 2007;14:57-9.  Back to cited text no. 42
Collins LC, Martyniak A, Kandel MJ, Stadler ZK, Masciari S, Miron A, et al. Basal Cytokeratin and Epidermal Growth Factor Receptor Expression are not predictive of BRCA1 mutation status in women with triple-negative breast cancers. Am J Surg Pathol 2009;33:1093-7.  Back to cited text no. 43
Lin C, Chien SY, Chen LS, Kuo SJ, Chang TW, Chen DR, et al. Triple negative breast carcinoma is a prognostic factor in Taiwanese women. BMC Cancer 2009;9:192.  Back to cited text no. 44
Gukas ID, Girling AC, Mandong BM, Prime W, Jennings BA, Leinster SJ, et al. Acomparison of clinicopathological features and molecular markers in British and Nigerian women with breast cancer. Clin Med Oncol 2008;2:347-51.  Back to cited text no. 45
Adisa AO, Arowolo OA, Akinkuolie AA, Titiloye NA, Alatise OI, Lawal OO, et al. Metastatic breast cancer in a Nigerian tertiary hospital. Afr Health Sci 2011;11:279-84.  Back to cited text no. 46
Mbonde MP, Amir H, Akslen LA, Kitinya JN. Expression of oestrogen and progesterone receptors, ki-67, p53 and BCL-2 proteins, cathepsin D, urokinase plasminogen activator and urokinase plasminogen activator-receptors in carcinomas of the female breast in an African population. East Afr Med J 2001;78:360-5.  Back to cited text no. 47
Iyare FE. Immunohistochemical characteristics of breast cancers in South East Nigeria. Ebonyi Med J 2007;6:9-12.  Back to cited text no. 48
Burstein HJ, Temin S, Anderson H, Buchholz TA, Davidson NE, Gelmon KE, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American society of clinical oncology clinical practice guideline focused update. J Clin Oncol 2014;32:2255-69.  Back to cited text no. 49
Ali MA, Sheta M, El Mohsen AM. Elevated serum and tissue VEGF associated with poor outcome in breast cancer patients. Alexandria J Med 2011;47:217-24.  Back to cited text no. 50
Ohene-Yeboah M, Adjei E. Breast cancer in Kumasi, Ghana. Ghana Med J 2012;46:8-13.  Back to cited text no. 51
Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. J Clin Oncol 2013;31:3997-4013.  Back to cited text no. 52
Lund MJ, Butler EN, Hair BY, Ward KC, Andrews JH, Oprea-Ilies G, et al. Age/race differences in HER2 testing and in incidence rates for breast cancer triple subtypes: A population-based study and first report. Cancer 2010;116:2549-59.  Back to cited text no. 53
Parise CA, Bauer KR, Brown MM, Caggiano V. Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999-2004. Breast J 2009;15:593-602.  Back to cited text no. 54
Jahanzeb M. Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer 2008;8:324-33.  Back to cited text no. 55
Ross JS, Fletcher JA. HER-2/neu (c-erb-B2) gene and protein in breast cancer. Am J Clin Pathol 1999;112:S53-67.  Back to cited text no. 56
Pathak TB, Bashyal R, Pun CB, Shrestha S, Bastola S, Neupane S, et al. Estrogen and progesterone receptor expression in breast cancer. J Pathol Nepal 2011;1:100-3.  Back to cited text no. 57
Baghat VM, Tha BM, Pathel PR. Correlation of hormonal receptor and Her2/Neu expression of breast cancer: Study at a tertiary care hospital in South-Gujarat. Natl J Med Res 2012;2:295-9.  Back to cited text no. 58
Rao C, Shetty J, Kishan Prasad HL. Morphological profile and receptor status in breast carcinoma: An institutional study. J Cancer Res Ther 2013;9:44-9.  Back to cited text no. 59


  [Figure 1]

  [Table 1], [Table 2], [Table 3]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    Materials and Me...
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded389    
    Comments [Add]    

Recommend this journal