Immunohistochemical Expression of Interleukin-17 and Hormonal Receptors in Benign and Malignant Breast Lesions

doi:10.21203/rs.3.rs-31991/v1

Download PDF

Research note

Immunohistochemical Expression of Interleukin-17 and Hormonal Receptors in Benign and Malignant Breast Lesions

https://doi.org/10.21203/rs.3.rs-31991/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 23 Jun, 2020

Read the published version in BMC Research Notes →

You are reading this older preprint version

Read the latest preprint version →

Objectives:IL17 is a critical pro-inflammatory cytokine that is involved in inflammation, multidrug resistance and growth persistence pathways in cancer. This study is aiming at studying the expression of IL17 and hormonal receptors expressionin benign and malignant breast lesions using immunohistochemical staining methods.

Results:A total of 137 cases of breast lesions were studied,97 (70.8%) were malignant and 40 (29.2%) were benign cases. Age range for malignant and benign cases were between 26 to 80 years [mean age 50±2 years], and 20 to 70 years[mean age 41±4 years], respectively, Odds ratio= 2.3 [1.78-1.99, 95% CI].The majority of the histopathological diagnosis of the benign and malignant lesions were 21 (15.3%) fibro-adenomas and 87 (63.5%) invasive ductal carcinoma, respectively. Expression of IL17 and age were insignificantly negatively correlated for both groups; benign cases [r= -0.054, P value 0.742] and malignant cases [r= -0.080, P value 0.444]. IL17 expression was showing insignificant association with age group, P value 0.065. IL17 expression showed a statistical significance based on the different histopathological diagnosis, P value 0.035. Expression levels of estrogen, progesterone, and human epidermal receptors were showing insignificant difference among IL17 expression categories, P values 0.678, 0.623, and 0.361, respectively.

Immunology

Cancer Biology

Interleukin-17

Immunohistochemistry

Breast Lesions

Breast Cancer

Breast cancer (BC) is one of the global prevalent malignancies among females [1]. According to 2019 cancer statistics, the incidence of BC is surprisingly increasing compared to earlier reports in 2018. Not surprisingly, the rate of mortality is very high in the African developing countries owing to socioeconomic factors [2]. Importantly, the majority of women in these countries were diagnosed at late stages of the disease that ominously, has been metastasized [2]. in a previous study, among 120 patients diagnosed with benign lesion and were followed up for almost 20 years, 34% of all palpable lesions were found to be malignant tumors followed by fibro-adenoma (28%), fibrocystic diseases (11%), inflammatory changes (11%), and other phylloid tumors and lactation changes (6%) [3]. According to the WHO there are several features in present in the benign lesions that are well known as pre-cancerous signs [4].

Metastasis and drug resistance constitute important problems in BC management and survival as well [5]. Lately, a number of studies have addressed the role of several mediators in determining the underlying mechanisms of BC invasion and persistence. These studies investigated the role of cytokines expression among both benign and malignant cancer patients, their finding was quite unique to further investigate the role of cytokines expression not only to understand the invasion mechanism, but also as diagnostic and prognostic markers for cancer development [6, 7].

Recently, cytokines and other ligands of immune system have been reported as instrumental factors in tumor microenvironment, and many of them are considered as prognostic and therapeutic targets in cancer [8, 9]. Basically, Interleukin-17 (IL17) is one of these important mediators which have strong potential mechanism to induce inflammation by enhancing several processes such as neutrophil migration, angiogenesis, and matrix metalloproteinase production [10–12]. In addition to its pivotal role in inflammation, IL17 can induce other important signaling pathways in tumor cell itself such as Kras and epithelial-mesenchymal transition which were reported as imperative pathways in cancer growth and metastasis [12–14]. IL17 was also involved by triggering several pathways in tumor that lead to growth persistence against cancer therapy [15].

Status of steroid and growth factor receptors expression such as Estrogen Receptor (ER), Progesterone Receptor (PR), and Hunan Epidermal Receptor-2 (HER2) play a key role in term of diagnosis and treatment of BC [16–18], since IL17 is directly related to production of steroid hormones and growth factors [19–21]. Consequently, the production of IL17 in tumor microenvironment suggested to play other significant clinical roles in BC development depending on receptors expression [19–21]. previous facts indicate a crucial role of IL17 in cancer initiation, prognosis and treatment, therefore, giving great interest to study its expression in benign and malignant breast lesions. This study is aiming at studying the expression of IL17 and hormonal expression in benign and malignant breast lesions using immunohistochemical staining methods.

Materials And Methods:

Study design and sample collection

A descriptive cross-sectional hospital-based study conducted in National Central Khartoum Lab between 2017 and 2018. Simple random sampling method has been done; to collect Archival paraffin blocks from 127 female patients diagnosed with any type of breast lesion. Patients' age and diagnosis were obtained from hospital`s record. Cancer grade and immunohistochemical expression of ER, PR, and HER2 for malignant cases were also obtained from the records which are done according to automated Ventana BanchMark XT system.

Paraffin sections preparation and Immunohistochemical Technique

One paraffin sections of 3–5 micrometers thickness was cut for IHC staining using rotary microtome. Immunohistochemical expression of IL17 was detected according to manufacturer instructions using the commercially available kit Mouse and Rabbit specific HRP/DAB Detection kit (ab64264, Abcam, Cambridge, UK). Briefly, tissue sections were de-waxed by xylene and rehydrated through gradients ethanol into water. For antigen retrieval, sections were heated in Citrate buffer (pH 6.0) for 20 minutes at 95 °C and quenched for endogenous peroxidase activity using 3% H₂O₂ in methyl alcohol. Sections were then washed in phosphate buffer saline (PBS) and the nonspecific binding of protein and antibody was blocked using protein block, then protein block was blotted off. Sections were incubated overnight at 4 ⁰C with primary antibody against IL17 (ab136668) at 1:100 dilution, after adjustment of the dilution and incubation period by using tonsil as a positive control for this antigen. After that, sections were washed with PBS then incubated with biotinylated secondary antibody. After several proper washes with washing buffer, the color was developed using HRP/DAP kit. Sections were lightly counterstained with hematoxylin and blued by running tap water, followed by dehydration and mounting in DPX.

Immunohistochemical Scoring System

The cytoplasmic staining scoring for IL17 in all tissue sections was performed semi-quantitatively based on the overall intensity of staining by two different pathologists into no expression, mild expression, moderate expression, and strong expression, according to the overall percentage of stained cells; no cells express the IL17, 10–30% of cells express IL17, 40–60% of cells express IL17, 60–80% of cells express IL17, and > 80% of the cells express IL17, respectively.

Statistical analysis:

Data were analysed using the Statistical Package for Social Science (SPSS, v16). Chi-Square test was used to analyze different categories. a P value of < 0.05 was considered statistically significant. Pearson correlation of IL17 expression in regards to age of cases and hormonal receptors expression besides Odds ratios were also calculated.

Patients demographics and sample categorization

The present study included 137 cases of breast lesions. Their age ranged between 20 to 80 years with a mean age of 47 ± 2 years. Notably, on categorizing patients by age, the age group 41 to 60 years constituted the majority of studied population 85 (62.0%), followed by 21 to 40 years 30 (21.9%). When categorizing the breast lesions-based malignancy, a total of 97 (70.8%) were malignant and 40 (29.2%) were benign. The malignant cases their age ranged between 26 to 80 years with a mean of 50 ± 2 years, whereas, the benign cases their age ranged between 20 to 70 years with a mean age of 41 ± 4 years, Odds ratio = 2.3 [1.78–1.99, 95% CI].

The benign cases based on the histopathological diagnosis included; fibro-adenomas (FA) which constituted the vast majority of the benign lesions 21 (15.3%), followed by duct ectasia (DE) 11 (8.0%), fibrocystic change (FC) 4 (2.9%), lipoma 2 (1.5%) and benign phylloid tumor (PTS) 2 (1.5%). While the malignant cases included 87 (63.5%) cases reported as invasive ductal carcinoma (IDC), 7 (5.1%) cases were invasive lobular carcinoma (ILC) and 3 (2.2%) cases were intraductal invasive carcinoma (IDIC). The type of breast lesion was statistically significant with age group, P value 0.003. as well, classification based on the histopathological examination was showing significant association when grouped according to age group, P value 0.000.

IL17 immunohistochemical expression

The expression of IL17 and age of cases were insignificantly negatively correlated for both groups; benign cases [r= -0.054, P value 0.742] and malignant cases [r= -0.080, P value 0.444]. According to the different age groups, the levels of IL17 expression among cases aged between 41 to 60 years, more than 60 years, and between 21 to 40 years were 29.4% strong, 47.1% moderate, and 16.7% mild, respectively. IL17 expression was showing insignificant association when categorized based on age groups, P value 0.065. IL17 was expressed in 63/97 (64.9%) of the malignant cases and 17 (42.5%) of the benign cases.

Mild expression of IL17 was noted among 22 (22.7%) of the malignant cases, while moderate expression was recorded among 10 (25.0%) of the benign cases and 15 (15.5%) of the malignant cases. Whereas benign and malignant cases recorded to show strong IL17 expression were 7 (17.5%) and 26 (26.8%), respectively (Fig. 1). A statistical significance was noted for the different expression categories among the benign and malignant cases, P value 0.002.

A strong expression of IL17 in malignant tissue sections was 28.7% among DC cases and 33.3% in IDC cases. For ILC cases, mild and moderate expression of IL17 was 28.6% for each. However, among the benign cases, DE and FA were mostly showing moderate expression; 36.4% and 28.6%, respectively. While phylloid and fibrocystic changes were showing strong expression; 100% and 50.0%, correspondingly. Benign cases which diagnosed histopathologically as lipoma did not showed any expression of IL17.

IL17 expression showed a statistical significance based on the different histopathological diagnosis, P value 0.035. With respect to hormonal receptors expression, the expression levels of ER, PR, and HER2 were showing insignificant difference among the different IL17 expression categories, P values 0.678, 0.623, and 0.361, respectively. The results of IL17 expression based on age groups, tumor type, histopathological diagnosis and hormonal receptors were illustrated in Table 1 (Table 1).

Table 1

IL17 expression based on age groups, tumor type, histopathological diagnosis, and hormonal receptors
	IL17 Expression				Total (n = 137)	P value
	No Expression	Mild	Moderate	Strong	Total (n = 137)	P value
Age Group
Not more than 20	1 (100%)	0 (0.0%)	0 (0.0%)	0 (0.0%)	1 (0.7%)	0.065
21 to 40 years	13 (43.3%)	5 (16.7%)	7 (23.3%)	5 (16.7%)	30 (21.9%)
41 to 60 years	38 (44.7%)	13 (15.3%)	9 (10.6%)	25 (29.4%)	85 (62.0%)
Above 60 years	5 (29.4%)	2 (11.8%)	8 (47.1%)	2 (11.8%)	17 (12.4%)
Tumor Type
Benign	23 (57.5%)	0 (0.0%)	10 (25.0%)	7 (17.5%)	40 (29.2%)	0.002
Malignant	34 (34.1%)	22 (22.7%)	15 (15.5%)	26 (26.8%)	97 (70.8%)	0.002
Diagnosis of Breast Lesion
IDC	30 (34.5%)	19 (21.8%)	13 (14.9%)	25 (28.7%)	87 (63.5%)	0.035
DE	7 (63.6%)	0 (0.0%)	4 (36.4%)	0 (0.0%)	11 (8.0%)
FA	12 (57.1%)	0 (0.0%)	6 (28.6%)	3 (14.3%)	21 (15.3%)
FC	2 (50.0%)	0 (0.0%)	0 (0.0%)	2 (50.0%)	4 (2.9%)
IDIC	2 (66.7%)	1 (33.3%)	0 (0.0%)	0 (0.0%)	3 (2.2%)
ILC	2 (28.6%)	2 (28.6%)	2 (28.6%)	1 (14.3%)	7 (5.1%)
Lipoma	2 (100%)	0 (0.0%)	0 (0.0%)	0 (0.0%)	2 (1.5%)
PTS	0 (0.0%)	0 (0.0%)	0 (0.0%)	2 (100%)	2 (1.5%)
ER*
Mild	10 (37.0%)	7 (25.9%)	3 (11.1%)	7 (25.9%)	27 (19.7%)	0.678
Moderate	3 (21.4%)	4 (28.6%)	4 (28.6%)	3 (21.4%)	14 (10.2%)
Strong	5 (29.4%)	5 (29.4%)	1 (5.9%)	6 (35.3%)	17 (12.4%)
No Expression	16 (41.0%)	6 (15.4%)	7 (17.9%)	10 (25.6%)	39 (28.5%)
PR*
Mild	9 (37.5%)	6 (25.0%)	3 (12.5%)	6 (25.0%)	24 (17.5%)	0.623
Moderate	3 (30.0%)	3 (30.0%)	1 (10.0%)	3 (30.0%)	10 (7.3%)
Strong	1 (8.3%)	3 (25.0%)	2 (16.7%)	6 (50.0%)	12 (8.8%)
No Expression	21 (41.2%)	10 (19.6%)	9 (17.6%)	11 (21.6%)	51 (37.2%)
HER2*
Mild	7 (35.0%)	7 (35.0%)	0 (0.0%)	6 (30.0%)	20 (14.6%)	0.361
Moderate	7 (46.7%)	2 (13.3%)	3 (20.0%)	3 (20.0%)	15 (10.9%)
Strong	8 (33.3%)	3 (12.5%)	4 (16.7%)	9 (37.5%)	24 (17.5%)
No Expression	12 (31.6%)	10 (26.3%)	8 (21.1%)	8 (21.1%)	38 (27.7%)
*ER: Estrogen Receptor, PR: Progesterone Receptor, HER2: Human Epidermal Receptor-2.

Concerning the correlation of ER, PR, and HER2 expression and IL17 expression in the breast lesions, no statistically significance correlation was shown for these receptors and IL17 expression (Table 2).

Table 2

The correlation of Estrogen receptor, Progesterone receptor, and Human epidermal receptor-2 expression with IL17 expression in the breast lesions.
	Pearson’s r	P value	95% CI [Lower bound - Upper bound]
Estrogen receptor	-0.001	0.993	2.70 [1.44–3.96]
Progesterone receptor	-0.024	0.813	2.93 [1.65–4.21]
Human epidermal receptor-2	0.043	0.679	2.83 [1.66–3.98]

Pro-inflammatory cytokines can play a key role in cancer microenvironment and some of these cytokines were associated with bad prognosis in breast cancer [20, 25, 26]. The current study has described the expression of IL17 in different subsets of benign and malignant lesions of the breast. Notably, malignant cases had strong positive expression in both number of cells and intensity of the reaction when compared with the benign ones. These findings were consistent with previous exhaustive studies pointing that IL17 is more associated with malignant breast lesions [27][28][29]. Furthermore, similar results were also stated in malignant and benign lesions in the thyroid and salivary gland cancers [30][31].

Benign lesions in this study were found to produce considerable levels of IL17 in epithelial cells of lobules; the highest production was detected in PTS and FA. Nonetheless, the data regarding cytokines expression in benign tumors is limited and strongly focused on FA subset of benign tumor; the most common benign lesions in the breast [32]. Thus, to our knowledge, this study is among the first to address IL17 among other breast lesions. Positive expression was also obtained in DE and FC in which expression was restricted to the inflammatory cells and stroma. In DE, the large numbers of foamy cells expressing IL17 might be attributed, mainly, to the inflammatory reactions associated with this condition [38].

The majority of studies demonstrated in-situ expression of IL17 in breast cancer along with T lymphocyte and innate immune cells being the main expression site for this cytokine in other types of cancers [39–41]. Recently IL17 was shown to be expressed by other cells like plasma cells and paneth cells in gut [42, 43]. However, in the current study the main site of IL17 expression was malignant cells themselves in addition to tumor stroma. This finding is in accordance with Li et al. [44] and Al-Samadi et al. [45] who found high prevalence of breast cancer and colon cancer cells expressing IL17, correspondingly.

Regarding the association between IL17 expression and hormonal expression (ER, PR and HER2) among malignant cases, the obtained results disclose no significant association between IL17 expression in breast tissue and the previously mentioned receptors (P values > .05). Conversely to our study, IL17 was more associated with ER- and triple negative BC [20][46]. However, in concordance to our study Chavey et al. [47] found that IL17 is one of the cytokines that are not related with steroid receptors expression. Furthermore, Slattery et al. [48] found that the relationship between cytokines and steroid receptors expression is affected by particular variants of cytokines with no association between IL17 variants and these receptors expression in the breast. Therefore, these results indicate that IL17 role in breast cancer might be independent of hormonal receptors expression.

IL17 is expressed in a variety of cell types including benign and malignant cells; most notably tumor cells in addition to tumor associated stromal cells. Malignant cells significantly express higher levels of IL17 when compared to benign tumor cells. These results indicate that the role of IL17 in BC might be independent of hormonal receptors expression.

This study evaluated the expression of IL17 in a small cohort of breast lesions, including benign and malignant lesions without providing dual staining to specify cells types.

Breast Cancer; DE:Duct Ectasia; ER:Estrogen Receptor; FA:Fibro-Adenomas; FC:Fibrocystic Change; HER2:Hunan Epidermal Receptor-2; IDC:Invasive Ductal Carcinoma; IDIC:Intraductal Invasive Carcinoma; IL17:Interleukin-17; ILC:Invasive Lobular Carcinoma; PBS:Phosphate Buffer Saline; PR:Progesterone Receptor; PTS:Benign Phylloid Tumor.

Ethics approval and consent to participate

Samples collection and conduction of the study was approved by the Faculty of Medical Laboratory Sciences Research Ethics Committee – University of Khartoum, Sudan. Informed consent was obtained from each participant prior to hospital enrollment using writing and verbal informed consent in case of illiterate patients.

Consent to publish

Not applicable

Availability of Data and Materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

Not applicable

Authors' contributions

ETA and MAMM performed samples collection and immunohistochemical technique regarding tissue samples. EES and AMME performed scoring and interpretation of immunohistochemical staining. MAMM and AMME performed general supervision and guidance in the research process. NSM, AA, and MSM performed data analysis and interpretation, ETA, EES, and NSM drafted the manuscript. All authors read and approved the final manuscript.

Acknowledgements

We gladly thank the staff of Medical Laboratory Sciences, University of Khartoum for their support and great help. And also great thanks to all participants contributed to this work.

Author’s Information

Eman Taha Ali

Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Khartoum, Sudan.

Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, National University, Sudan. Email: [email protected]

Mai Abdulrahman Mohammed Masri

Molecular Biology Department, Faculty of Zoology, University of Khartoum, Khartoum, Sudan. Email: [email protected]

Emmanuel Edwar Siddig

Research Assistant, Mycetoma Research Center, University of Khartoum, Khartoum, Sudan.

Nile College – School of medicine, Khartoum, Sudan

Department of Histopathology and Cytology, Alfarrabi College for Science and Technology, Khartoum, Sudan. Email: [email protected]

Ayman Ahmed

Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan. Email: [email protected]

Mohamed S. Muneer

Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.

Department of Radiology, Mayo Clinic, Jacksonville, FL, USA

Department of Internal Medicine, Faculty of Medicine, University of Khartoum, Khartoum, Sudan. Email: [email protected]

Nouh Saad Mohamed

Department of Parasitology and Medical Entomology, Alfarrabi College for Science and Technology, Khartoum, Sudan.

Departments of Parasitology and Medical Entomology, Faculty of Medical Laboratory Sciences, Nile University, Khartoum, Sudan

Department of Parasitology, Faculty of Medicine, Sinnar University, Sinnar, Sudan. Email: [email protected]

Ali Mahmoud Mohammed Edris

Department of Histopathology and Cytology, Faculty of Medical Laboratory Sciences, University of Khartoum, Khartoum, Sudan

Department of Histopathology and Cytology, Faculty of Applied Medical Sciences, University of Bisha, Bisha, Kingdom of Saudi Arabia. Email: [email protected]

Azim HA, Partridge AH. Biology of breast cancer in young women. Breast cancer research. 2014;16:427.
Lodge M, Corbex M. Establishing an evidence-base for breast cancer control in developing countries. The Breast. 2011;20:65–9.
Shaaban A, Sloane J, West C, Moore F, Jarvis C, Williams E, Foster C. Histopathologic types of benign breast lesions and the risk of breast cancer: case–control study. Am J Surg Pathol. 2002;26:421–30.
Weigelt B, Peterse JL, Van't Veer LJ. Breast cancer metastasis: markers and models. Nature reviews cancer. 2005;5:591–602.
Gelaleti GB, Jardim BV, Leonel C, Moschetta MG, de Campos Zuccari DAP. Interleukin-8 as a prognostic serum marker in canine mammary gland neoplasias. Veterinary immunology immunopathology. 2012;146:106–12.
Al-Hassan A, Al-Ghurabi B, Al-Karkhi I. Prognostic value of proinflammatory cytokines in breast cancer. Biomol Res Ther. 2012;1:2.
Ueno T, Toi M, Saji H, Muta M, Bando H, Kuroi K, Koike M, Inadera H, Matsushima K. Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. Clinical cancer research. 2000;6:3282–9.
Guo Y, Xu F, Lu T, Duan Z, Zhang Z. Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer treatment reviews. 2012;38:904–10.
Chen WC, Lai YH, Chen HY, Guo HR, Su IJ, Chen HH. Interleukin-17‐producing cell infiltration in the breast cancer tumour microenvironment is a poor prognostic factor. Histopathology. 2013;63:225–33.
Numasaki M, Fukushi J-i, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT. Interleukin-17 promotes angiogenesis and tumor growth. Blood The Journal of the American Society of Hematology. 2003;101:2620–7.
Feng M, Wang Y, Chen K, Bian Z, Wu J, Gao Q. IL-17A promotes the migration and invasiveness of cervical cancer cells by coordinately activating MMPs expression via the p38/NF-κB signal pathway. PLoS One 2014, 9.
McAllister F, Bailey JM, Alsina J, Nirschl CJ, Sharma R, Fan H, Rattigan Y, Roeser JC, Lankapalli RH, Zhang H. Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia. Cancer cell. 2014;25:621–37.
Chang SH. Tumorigenic Th17 cells in oncogenic Kras-driven and inflammation-accelerated lung cancer. Oncoimmunology. 2015;4:e955704.
Jiang Y, Yang S, Li P, Luo X, Li Z, Hao Y, Yu P. The promotion of the transformation of quiescent gastric cancer stem cells by IL-17 and the underlying mechanisms. Oncogene. 2017;36:1256–64.
Cochaud S, Giustiniani J, Thomas C, Laprevotte E, Garbar C, Savoye A-M, Curé H, Mascaux C, Alberici G, Bonnefoy N. IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2. Scientific reports. 2013;3:3456.
Park WC, Sung KS, Kim JS, Oh SJ, Choi SH, You YK, Chun HM, Kim IC, Jung SS. Prognostic Significance of Hormonal Receptors in Very Young Women with Early Breast Cancer. Journal of Korean Breast Cancer Society. 2002;5:319–22.
Vorherr H. Endocrinology of breast cancer. Maturitas. 1987;9:113–22.
Hoang T, Rattan R. Common uses of immunohistochemistry in interpreting lesions of the breast: a pictorial review. Breast Cancer Res. 2008;10:P87.
Ramirez F, Fowell D, Puklavec M, Simmonds S, Mason D. Glucocorticoids promote a Th2 cytokine response by CD4 + T cells in vitro. J Immunol. 1996;156:2406–12.
Chen WC, Lai YH, Chen HY, Guo HR, Su IJ, Chen HHJH. Interleukin-17‐producing cell infiltration in the breast cancer tumour microenvironment is a poor prognostic factor. 2013, 63:225–233.
Chavey C, Bibeau F, Gourgou-Bourgade S, Burlinchon S, Boissière F, Laune D, Roques S, Lazennec G. Oestrogen receptor negative breast cancers exhibit high cytokine content. Breast Cancer Res. 2007;9:R15.
Eaton K, Yang W. Registered report: Intestinal inflammation targets cancer-inducing activity of the microbiota. elife. 2015;4:e04186.
Kunts T, Karpukhina K, Mikhailova E, Varaksin N, Autenshlyus A. P64: Cytokine production by malignant and benign breast tumors. Eur J Cancer Suppl. 2015;13:30.
Al-Hassan A, Al-Ghurabi B, Al-Karkhi IJJBRT. Prognostic value of proinflammatory cytokines in breast cancer. 2012, 1:2.
Ueno T, Toi M, Saji H, Muta M, Bando H, Kuroi K, Koike M, Inadera H. Matsushima KJCcr: Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer. 2000, 6:3282–3289.
Guo Y, Xu F, Lu T, Duan Z, Zhang ZJCtr. Interleukin-6 signaling pathway in targeted therapy for cancer. 2012, 38:904–910.
Autenshlyus A, Kunts T, Karpukhina K, Mikhaylova E, Varaksin N, Marinkin I, Lyakhovich V. Cytokine pattern of the breast tumor supernatant. In Doklady Biological SciencesSpringer; 2016: 247–248.
Borj MR, Andalib AR, Mohammadi A, Hoseiniharouni SM, Pourghadamyari H, Azizi H, Golmahammadi T, Ghahfarokhy KM. Evaluation of IL-4, IL-17, and IFN-γ Levels in PatientsWith Breast Cancer. International Journal of Basic Science in Medicine. 2017;2:20–4.
Carvalho G, Faria D, Zanetti BR, Miranda L, Hassumi–Fukasawa MK, Miranda–Camargo F, Crispim JCO, Soares EG. High IL-17 expression is associated with an unfavorable prognosis in thyroid cancer. Oncology letters. 2017;13:1925–31.
Haghshenas MR, Khademi B, Faghih Z, Ghaderi A, Erfani N. Immune regulatory cells and IL17-producing lymphocytes in patients with benign and malignant salivary gland tumors. Immunology letters. 2015;164:109–16.
Elgaili EM, Abuidris DO, Rahman M, Michalek AM, Mohammed SI. Breast cancer burden in central Sudan. International journal of women's health. 2010;2:77.
Gary MT, Chaiwun B, Lau K-M, Scolyer R, Lee CS, Karim RZ, Putti TC, Law BK, Lui PC, Tan PH. Endothelin-1 expression correlates with atypical histological features in mammary phyllodes tumours. J Clin Pathol. 2007;60:1051–6.
Borj MR, Andalib AR, Mohammadi A, Hoseiniharouni SM, Pourghadamyari H, Azizi H, Golmahammadi T. Ghahfarokhy KMJIJoBSiM: Evaluation of IL-4, IL-17, and IFN-γ Levels in PatientsWith Breast Cancer. 2017, 2:20–24.
Gary M, Lui PC, Lee CS, Kung FY, Scolyer RA, Law BK, Lau T-S, Karim R, Putti TC. Stromal expression of vascular endothelial growth factor correlates with tumor grade and microvessel density in mammary phyllodes tumors: a multicenter study of 185 cases. Human pathology. 2004;35:1053–7.
Numasaki M, Fukushi J-i, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MTJB. The Journal of the American Society of Hematology: Interleukin-17 promotes angiogenesis and tumor growth. 2003, 101:2620–2627.
Gary M, Lui PC, Lee CS, Kung FY, Scolyer RA, Law BK, Lau T-S, Karim R, Putti TCJHp. Stromal expression of vascular endothelial growth factor correlates with tumor grade and microvessel density in mammary phyllodes tumors: a multicenter study of 185 cases. 2004, 35:1053–1057.
Dixon J, Ravisekar O, Chetty U, Anderson T. Periductal mastitis and duct ectasia: different conditions with different aetiologies. Br J Surg. 1996;83:820–2.
Dixon J, Ravisekar O, Chetty U, Anderson TJBJoS. Periductal mastitis and duct ectasia: different conditions with different aetiologies. 1996, 83:820–822.
Kuang DM, Peng C, Zhao Q, Wu Y, Chen MS, Zheng L. Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells. Hepatology. 2010;51:154–64.
Guéry L, Hugues S: Th17 cell plasticity and functions in cancer immunity. BioMed research international 2015, 2015.
Wu S, Rhee K-J, Albesiano E, Rabizadeh S, Wu X, Yen H-R, Huso DL, Brancati FL, Wick E, McAllister F. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nature medicine. 2009;15:1016.
Takahashi N, Vanlaere I, De Rycke R, Cauwels A, Joosten LA, Lubberts E, van den Berg WB, Libert C. IL-17 produced by Paneth cells drives TNF-induced shock. The Journal of experimental medicine. 2008;205:1755–61.
Schlegel PM, Steiert I, Kötter I, Müller CA. B cells contribute to heterogeneity of IL-17 producing cells in rheumatoid arthritis and healthy controls. PloS one 2013, 8.
Li YX, Zhang L, Simayi D, Zhang N, Tao L, Yang L, Zhao J, Chen YZ, Li F, Zhang WJ. Human papillomavirus infection correlates with inflammatory Stat3 signaling activity and IL-17 level in patients with colorectal cancer. PLoS One 2015, 10.
Al-Samadi A, Moossavi S, Salem A, Sotoudeh M, Tuovinen SM, Konttinen YT, Salo T, Bishehsari F. Distinctive expression pattern of interleukin-17 cytokine family members in colorectal cancer. Tumor Biology. 2016;37:1609–15.
Cochaud S, Giustiniani J, Thomas C, Laprevotte E, Garbar C, Savoye A-M, Curé H, Mascaux C, Alberici G, Bonnefoy NJSr: IL-17A is produced by breast cancer TILs and promotes chemoresistance and proliferation through ERK1/2. 2013, 3:3456.
Chavey C, Bibeau F, Gourgou-Bourgade S, Burlinchon S, Boissière F, Laune D, Roques S, Lazennec GJBCR. Oestrogen receptor negative breast cancers exhibit high cytokine content. 2007, 9:R15.
Slattery ML, Herrick JS, Torres-Mejia G, John EM, Giuliano AR, Hines LM, Stern MC, Baumgartner KB, Presson AP, Wolff RK. Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the Breast Cancer Health Disparities Study. Carcinogenesis. 2014;35:1750–9.

Download PDF

Journal Publication

published 23 Jun, 2020

Read the published version in BMC Research Notes →

Editorial decision: Minor revision
07 Jun, 2020
Reviewer #1 agreed at journal
01 Jun, 2020
Review #1 received at journal
01 Jun, 2020
Submission checks completed at journal
28 May, 2020
Editor invited by journal
28 May, 2020
Editor assigned by journal
28 May, 2020
Reviewers invited by journal
28 May, 2020
First submitted to journal
26 May, 2020

You are reading this older preprint version

Read the latest preprint version →

Immunohistochemical Expression of Interleukin-17 and Hormonal Receptors in Benign and Malignant Breast Lesions

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction:

Main Text:

Materials And Methods:

Study design and sample collection

Paraffin sections preparation and Immunohistochemical Technique

Immunohistochemical Scoring System

Statistical analysis:

Results:

Patients demographics and sample categorization

Discussion:

Conclusion:

Limitations:

Abbreviations

Declarations

Ethics approval and consent to participate

Consent to publish

Availability of Data and Materials

Competing interests

Funding

Authors' contributions

Acknowledgements

Author’s Information

References

Status:

Journal Publication

Version 1