Immunoexpression of lactoferrin in triple-negative breast cancer patients: A proposal to select a less aggressive subgroup

Ieni,Antonio; Barresi,Valeria; Licata,Luana; Cardia,Roberta; Fazzari,Carmine; Nuciforo,Giuseppe; Caruso,Francesco; Caruso,Michele; Adamo,Vincenzo; Tuccari,Giovanni

doi:10.3892/ol.2017.5859

Immunoexpression of lactoferrin in triple-negative breast cancer patients: A proposal to select a less aggressive subgroup

Authors:
- Antonio Ieni
- Valeria Barresi
- Luana Licata
- Roberta Cardia
- Carmine Fazzari
- Giuseppe Nuciforo
- Francesco Caruso
- Michele Caruso
- Vincenzo Adamo
- Giovanni Tuccari
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Affiliations: Department of Human Pathology of Adult and Evolutive Age ‘Gaetano Barresi’, Polyclinic ‘G. Martino’, University of Messina, I‑98125 Messina, Italy, Department of Pathological Anatomy, Humanitas Catanese Center of Oncology, I‑95126 Catania, Italy, Department of Oncological Surgery, Humanitas Catanese Center of Oncology, I‑95126 Catania, Italy, Department of Oncology, Humanitas Catanese Center of Oncology, I‑95126 Catania, Italy
Published online on: March 14, 2017 https://doi.org/10.3892/ol.2017.5859
Pages: 3205-3209

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Abstract

Triple-negative breast cancer (TNBC) indicates a subset of breast carcinomas that does not express estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor‑2 (HER2). According to the literature, TNBCs are aggressive tumors, characterized by a high incidence of recurrence and a high risk of disease progression. Lactoferrin (LF) is a single‑chain, iron‑binding glycoprotein of ~700 amino acids, which is involved in a wide range of biological activities, including iron‑trafficking and carcinogenesis. The present study aimed to assess LF expression in human TNBC samples and the possible correlation with clinico‑pathological parameters associated with biological aggressiveness. LF immunohistochemical expression was investigated in formalin‑fixed, paraffin‑embedded samples of human TNBC. Cases were analyzed according to an intensity distribution (ID) score, and only those showing an ID score of >2 were considered as positive for LF. LF immunostaining was encountered in 26.15% cases. A significant correlation was found between LF expression and a low Ki‑67 labeling index (P=0.040), the absence of recurrence (P=0.010) and alive status (P=0.020). LF may assist in identifying a subset of TNBC with less aggressive biological behavior. The meaning of LF expression in TNBC remains unclear and is controversial. The present findings indicated that LF expression is correlated with a low growth fraction in these tumors. Thus, it is possible that the inhibition of the LF axis may be a valid therapeutic target for TNBC, and this should be confirmed by future studies.

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1	Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, He X and Perou CM: Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 12:R682010. View Article : Google Scholar : PubMed/NCBI
2	Perou CM: Molecular stratification of triple-negative breast cancers. Oncologist. 16:(Suppl 1). S61–S70. 2011. View Article : Google Scholar
3	Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y and Pietenpol JA: Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 121:2750–2767. 2011. View Article : Google Scholar : PubMed/NCBI
4	Lehmann BD, Bauer JA, Schafer JM, Pendleton CS, Tang L, Johnson KC, Chen X, Balko JM, Gómez H, Arteaga CL, et al: PIK3CA mutations in androgen receptor-positive triple negative breast cancer confer sensitivity to the combination of PI3K and androgen receptor inhibitors. Breast Cancer Res. 16:4062014. View Article : Google Scholar : PubMed/NCBI
5	Kashiwagi S, Yashiro M, Takashima T, Nomura S, Noda S, Kawajiri H, Ishikawa T, Wakasa K and Hirakawa K: Significance of E-cadherin expression in triple-negative breast cancer. Br J Cancer. 103:249–255. 2010. View Article : Google Scholar : PubMed/NCBI
6	Ricciardi GR, Adamo B, Ieni A, Licata L, Cardia R, Ferraro G, Franchina T, Tuccari G and Adamo V: Correction: Androgen receptor (AR), E-Cadherin, and Ki-67 as emerging targets and novel prognostic markers in triple-negative breast cancer (TNBC) patients. PLoS One. 10:e01326472015. View Article : Google Scholar : PubMed/NCBI
7	Safarpour D and Tavassoli FA: A targetable androgen receptor-positive breast cancer subtype hidden among the triple-negative cancers. Arch Pathol Lab Med. 139:612–617. 2015. View Article : Google Scholar : PubMed/NCBI
8	Abd-Elazeem MA and Abd-Elazeem MA: Claudin 4 expression in triple-negative breast cancer: Correlation with androgen receptors and Ki-67 expression. Ann Diagn Pathol. 19:37–42. 2015. View Article : Google Scholar : PubMed/NCBI
9	Caselitz J, Jaup T and Seifert G: Lactoferrin and lysozyme in carcinomas of the parotid gland. A comparative immunocytochemical study with the occurrence in normal and inflamed tissue. Virchows Arch A Pathol Anat Histol. 394:61–73. 1981. View Article : Google Scholar : PubMed/NCBI
10	Tuccari G and Barresi G: Immunohistochemical demonstration of lactoferrin in follicular adenomas and thyroid carcinomas. Virchows Arch A Pathol Anat Histopathol. 406:67–74. 1985. View Article : Google Scholar : PubMed/NCBI
11	Cabaret V, Vilain MO, Delobelle-Deroide A and Vanseymortier L: Immunohistochemical demonstration of ceruloplasmin and lactoferrin in a series of 59 thyroid tumors. Ann Pathol. 12:347–352. 1992.(In French). PubMed/NCBI
12	Tuccari G, Giuffrè G, Crisafulli C and Barresi G: Immuno-histochemical detection of lactoferrin in human astrocytomas and multiforme glioblastomas. Eur J Histochem. 43:317–322. 1999.PubMed/NCBI
13	Zhou Y, Zeng Z, Zhang W, Xiong W, Wu M, Tan Y, Yi W, Xiao L, Li X, Huang C, et al: Lactotransferrin: A candidate tumor suppressor-Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen-activated protein kinase pathway. Int J Cancer. 123:2065–2072. 2008. View Article : Google Scholar : PubMed/NCBI
14	Tuccari G, Barresi G, Arena F and Inferrera C: Immuno-cytochemical detection of lactoferrin in human gastric carcinomas and adenomas. Arch Pathol Lab Med. 113:912–915. 1989.PubMed/NCBI
15	Walmer DK, Padin CJ, Wrona MA, Healy BE, Bentley RC, Tsao MS, Kohler MF, McLachlan JA and Gray KD: Malignant transformation of the human endometrium is associated with overexpression of lactoferrin messenger RNA and protein. Cancer Res. 55:1168–1175. 1995.PubMed/NCBI
16	Farley J, Loup D, Nelson M, Mitchell A, Esplund G, Macri C, Harrison C and Gray K: Neoplastic transformation of the endocervix associated with downregulation of lactoferrin expression. Mol Carcinog. 20:240–250. 1997. View Article : Google Scholar : PubMed/NCBI
17	Giuffrè G, Arena F, Scarfì R, Simone A, Todaro P and Tuccari G: Lactoferrin immunoexpression in endometrial carcinomas: Relationships with sex steroid hormone receptors (ER and PR), proliferation indices (Ki-67 and AgNOR) and survival. Oncol Rep. 16:257–263. 2006.PubMed/NCBI
18	Giuffrè G, Barresi V, Skliros C, Barresi G and Tuccari G: Immunoexpression of lactoferrin in human sporadic renal cell carcinomas. Oncol Rep. 17:1021–1026. 2007.PubMed/NCBI
19	Tuccari G, Giuffrè G, Scarfì R, Simone A, Todaro P and Barresi G: Immunolocalization of lactoferrin in surgically resected pigmented skin lesions. Eur J Histochem. 49:33–38. 2005. View Article : Google Scholar : PubMed/NCBI
20	Ieni A, Barresi V, Grosso M, Rosa MA and Tuccari G: Immuno-localization of lactoferrin in cartilage-forming neoplasms. J Orthop Sci. 14:732–737. 2009. View Article : Google Scholar : PubMed/NCBI
21	Ieni A, Barresi V, Grosso M, Rosa MA and Tuccari G: Lactoferrin immuno-expression in human normal and neoplastic bone tissue. J Bone Miner Metab. 27:364–371. 2009. View Article : Google Scholar : PubMed/NCBI
22	Ieni A, Barresi V, Branca G, Giuffrè G, Rosa MA and Tuccari G: Immunoexpression of lactoferrin in bone metastases and corresponding primary carcinomas. Oncol Lett. 5:1536–1540. 2013.PubMed/NCBI
23	Charpin C, Lachard A, Pourreau-Schneider N, Jacquemier J, Lavaut MN, Andonian C, Martin PM and Toga M: Localization of lactoferrin and nonspecific cross-reacting antigen in human breast carcinomas. An immunohistochemical study using the avidin-biotinperoxidase complex method. Cancer. 55:2612–2617. 1985. View Article : Google Scholar : PubMed/NCBI
24	Ha NH, Nair VS, Reddy DN, Mudvari P, Ohshiro K, Ghanta KS, Pakala SB, Li DQ, Costa L, Lipton A, et al: Lactoferrin endothelin-1 axis contributes to the development and invasiveness of triple-negative breast cancer phenotypes. Cancer Res. 71:7259–7269. 2011. View Article : Google Scholar : PubMed/NCBI
25	Tuccari G and Barresi G: Lactoferrin in human tumours: Immunohistochemical investigations during more than 25 years. Biometals. 24:775–784. 2011. View Article : Google Scholar : PubMed/NCBI
26	Penco S, Caligo MA, Cipollini G, Bevilacqua G and Garré C: Lactoferrin expression in human breast cancer. Cancer Biochem Biophys. 17:163–178. 1999.PubMed/NCBI
27	Benaïssa M, Peyrat JP, Hornez L, Mariller C, Mazurier J and Pierce A: Expression and prognostic value of lactoferrin mRNA isoforms in human breast cancer. Int J Cancer. 114:299–306. 2005. View Article : Google Scholar : PubMed/NCBI
28	Ieni A and Tuccari G: Comments on the ‘Prognostic impact and clinicopathological correlation of CD133 and ALDH1 expression in invasive breast cancer’. J Breast Cancer. 19:96–98. 2016. View Article : Google Scholar : PubMed/NCBI
29	Ieni A, Barresi V, Branca G, Giuffrè G, Rosa MA and Tuccari G: Immunohistochemical Investigation of lactoferrin in human bone primary and metastatic tumours. Int J Lab Med Res. 1:IJLMR-105.
30	Ieni A, Giuffrè G, Lanzafame S, Nuciforo G, Curduman M, Villari L, Roz E, Certo G, Cabibi D, Salomone E, et al: Morphological and biomolecular characteristics of subcentimetric invasive breast carcinomas in Sicily: A multicentre retrospective study in relation to trastuzumab treatment. Oncol Lett. 3:141–146. 2012.PubMed/NCBI
31	Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B and Senn HJ: Panel members: Personalizing the treatment of women with early breast cancer: Highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 24:2206–2223. 2013. View Article : Google Scholar : PubMed/NCBI
32	Ieni A, Barresi V, Ricciardi GR, Adamo B, Adamo V and Tuccari G: Prognostic value of androgen receptor expression in triple negative breast carcinomas: Personal experience and comments on a review about ‘Triple-negative breast cancer: Treatment challenges and solutions’ by Collignon et al. Breast Cancer (Dove Med Press). 8:157–159. 2016.PubMed/NCBI
33	Rakha EA, El-Sayed ME, Green AR, Lee AH, Robertson JF and Ellis IO: Prognostic markers in triple-negative breast cancer. Cancer. 109:25–32. 2007. View Article : Google Scholar : PubMed/NCBI