To study the immunohistochemical expression of CD74 in series of invasive breast carcinomas classified according to their estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) immunoprofile and explore its correlation to Nottingham Prognostic Index (NPI) and tumor pathologic stage to determine if it has a prognostic value.
Methods
A total of 160 cases of mammary carcinoma were classified broadly according to their ER, PR, and HER2 expression into luminal, HER2-positive, and triple-negative groups. The NPI was calculated and pathologic stage was recorded for each individual case and cases were classified into different prognostic groups. The CD74 expression was evaluated immunohistochemically and correlated to different prognostic variables.
Results
The CD74 immunohistochemical expression in invasive breast carcinoma was significantly higher in triple-negative tumors, higher tumor grades, presence of lymph nodal metastasis, higher tumor stages, and higher NPI scores.
Conclusions
The CD74 might be a useful prognostic indicator predicting poor outcome of patients with breast carcinoma. Its consistent expression in triple-negative breast carcinomas points to the need of further studies to test the possibility if it can be targeted in treatment of breast carcinoma, especially in such groups.
Get full access to this article
View all access options for this article.
References
1.
TianBZhangYLiNLiuXDongJCD74: a potential novel target for triple-negative breast cancer. Tumour Biol. 2012;33 (6): 2273–2277.
2.
PerouCMMolecular stratification of triple-negative breast cancers. Oncologist. 2011;16 (Suppl 1):61–70.
3.
ZagonISPorterfieldNKMcLaughlinPJOpioid growth factor - opioid growth factor receptor axis inhibits proliferation of triple negative breast cancer. Exp Biol Med (Maywood). 2013;238 (6):589–599.
4.
GoldDVSteinRBurtonJGoldenbergDMEnhanced expression of CD74 in gastrointestinal cancers and benign tissues. Int J Clin Exp Pathol. 2010;4 (1):1–12.
5.
BurtonJDElySReddyPKCD74 is expressed by multiple myeloma and is a promising target for therapy. Clin Cancer Res. 2004;10 (19):6606–6611.
6.
SteinRQuZCardilloTMAntiproliferative activity of a humanized anti-CD74 monoclonal antibody, hLL1, on B-cell malignancies. Blood. 2004;104 (12):3705–3711.
7.
IshigamiSNatsugoeSTokudaKInvariant chain expression in gastric cancer. Cancer Lett. 2001;168 (1):87–91.
8.
HustinxSRCaoDMaitraADifferentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression. Cancer Biol Ther. 2004;3 (12): 1254–1261.
9.
CuthbertRJWilsonJMScottNColettaPLHullMADifferential CD74 (major histocompatibility complex Class II invariant chain) expression in mouse and human intestinal adenomas. Eur J Cancer. 2009;45 (9):1654–1663.
10.
YoungANAminMBMorenoCSExpression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers. Am J Pathol. 2001;158 (5):1639–1651.
11.
McClellandMZhaoLCarskadonSArenbergDExpression of CD74, the receptor for macrophage migration inhibitory factor, in non-small cell lung cancer. Am J Pathol. 2009;174 (2):638–646.
12.
KitangeGJCarlsonBLSchroederMAExpression of CD74 in high grade gliomas: a potential role in temozolomide resistance. J Neurooncol. 2010;100 (2):177–186.
13.
ChamuleauMESouwerYVan HamSMClass II-associated invariant chain peptide expression on myeloid leukemic blasts predicts poor clinical outcome. Cancer Res. 2004;64 (16):5546–5550.
14.
KoideNYamadaTShibataREstablishment of perineural invasion models and analysis of gene expression revealed an invariant chain (CD74) as a possible molecule involved in perineural invasion in pancreatic cancer. Clin Cancer Res. 2006; 12 (8):2419–2426.
15.
SteinRMattesMJCardilloTMCD74: a new candidate target for the immunotherapy of B-cell neoplasms. Clin Cancer Res. 2007;13 (18 Pt 2):5556s–5563s.
16.
VerjansENoetzelEBektasNDual role of macrophage migration inhibitory factor (MIF) in human breast cancer. BMC Cancer. 2009;9 (1):230.
17.
LakhaniSREllisIOSchnittSJTanPHvan de VijverMJWHO classification of tumours of the breast; International Agency for Research on Cancer; World Health Organization. LyonInternational Agency for Research on Cancer2012; 1-240.
18.
ElstonCWEllisIOPathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19 (5):403–410.
19.
RakhaEAEl-SayedMELeeAHPrognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol. 2008;26 (19):3153–3158.
20.
PratAParkerJSKarginovaOPhenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 2010;12 (5):R68.
21.
McCartyKSJrSzaboEFlowersJLUse of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res. 1986;46 (8) (Suppl): 4244s–4248s.
22.
OkugawaHYamamotoDUemuraYPrognostic factors in breast cancer: the value of the Nottingham Prognostic Index for patients treated in a single institution. Surg Today. 2005;35 (11):907–911.
23.
GoldhirschAWoodWCCoatesASGelberRDThürlimannBSennHJPanel members. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22 (8):1736–1747.
24.
MannGBFaheyVDFeleppaFBuchananMRReliance on hormone receptor assays of surgical specimens may compromise outcome in patients with breast cancer. J Clin Oncol. 2005;23 (22):5148–5154.
25.
FoulkesWDSmithIEReis-FilhoJSTriple-negative breast cancer. N Engl J Med. 2010;363 (20):1938–1948.
26.
RakhaEAReis-FilhoJSBaehnerFBreast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res. 2010;12 (4):207–218.
27.
RakhaEASoriaDGreenARNottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer. Br J Cancer. 2014;110 (7):1688–1697.
28.
DunklerDMichielsSSchemperMGene expression profiling: does it add predictive accuracy to clinical characteristics in cancer prognosis?Eur J Cancer. 2007;43 (4):745–751.
29.
SoriaDGaribaldiJMAmbrogiFA methodology to identify consensus classes from clustering algorithms applied to immunohistochemical data from breast cancer patients. Comput Biol Med. 2010;40 (3):318–330.
30.
BakerEAStephensonTJReedMWBrownNJExpression of proteinases and inhibitors in human breast cancer progression and survival. Mol Pathol. 2002;55 (5):300–304.
31.
MeteogluIDikiciogluEErkusMBreast carcinogensis Transition between hypersensitivity and invasive lesions. Saudi Med J. 2005;26 (12):1889–1896.
32.
RakhaEAEl-SayedMEGreenARLeeAHRobertsonJFEllisIOPrognostic markers in triple-negative breast cancer. Cancer. 2007;109 (1):25–32.
33.
SapraPSteinRPickettJAnti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys. Clin Cancer Res. 2005;11 (14):5257–5264.
34.
StarletsDGoreYBinskyICell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival. Blood. 2006;107 (12):4807–4816.
35.
GreenwoodCMetodievaGAl-JanabiKStat1 and CD74 overexpression is co-dependent and linked to increased invasion and lymph node metastasis in triple-negative breast cancer. J Proteomics. 2012;75 (10):3031–3040.
36.
MetodievaGNogueira-de-SouzaNCGreenwoodCCD74-dependent deregulation of the tumor suppressor scribble in human epithelial and breast cancer cells. Neoplasia. 2013;156: 660–668.
37.
IshigamiSNatsugoeSTokudaKInvariant chain expression in gastric cancer. Cancer Lett. 2001;168 (1):87–91.
38.
CuthbertRJWilsonJMScottNColettaPLHullMADifferential CD74 (major histocompatibility complex Class II invariant chain) expression in mouse and human intestinal adenomas. Eur J Cancer. 2009;45 (9):1654–1663.
39.
KoideNYamadaTShibataREstablishment of perineural invasion models and analysis of gene expression revealed an invariant chain (CD74) as a possible molecule involved in perineural invasion in pancreatic cancer. Clin Cancer Res. 2006;128: 2419–2426.
40.
LengLMetzCNFangYMIF signal transduction initiated by binding to CD74. J Exp Med. 2003;197 (11):1467–1476.
41.
ShiXLengLWangTCD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. Immunity. 2006;25 (4):595–606.
42.
ZhangJFHuaRLiuDJLiuWHuoYMSunYWEffect of CD74 on the prognosis of patients with resectable pancreatic cancer. Hepatobiliary Pancreat Dis Int. 2014;13 (1):81–86.
43.
DattaMWShahsafaeiANadlerLMFreemanGJDorfmanDMExpression of MHC class II-associated invariant chain (Ii;CD74) in thymic epithelial neoplasms. Appl Immunohistochem Mol Morphol. 2000;8 (3):210–215.
44.
Meyer-SieglerKLIczkowskiKAVeraPLFurther evidence for increased macrophage migration inhibitory factor expression in prostate cancer. BMC Cancer. 2005;5 (1):73.
45.
Meyer-SieglerKLIczkowskiKALengLBucalaRVeraPLInhibition of macrophage migration inhibitory factor or its receptor (CD74) attenuates growth and invasion of DU-145 prostate cancer cells. J Immunol. 2006;177 (12):8730–8739.
46.
BinskyIHaranMStarletsDIL-8 secreted in a macrophage migration-inhibitory factor- and CD74-dependent manner regulates B cell chronic lymphocytic leukemia survival. Proc Natl Acad Sci USA. 2007;104 (33):13408–13413.
47.
McClellandMZhaoLCarskadonSArenbergDExpression of CD74, the receptor for macrophage migration inhibitory factor, in non-small cell lung cancer. Am J Pathol. 2009;174 (2):638–646.
48.
NagataSJinYFYoshizatoKCD74 is a novel prognostic factor for patients with pancreatic cancer receiving multimodal therapy. Ann Surg Oncol. 2009;16 (9):2531–2538.
49.
OtterstromCSoltermannAOpitzICD74: a new prognostic factor for patients with malignant pleural mesothelioma. Br J Cancer. 2014;110 (8):2040–2046.
50.
BorgheseFClanchyFICD74: an emerging opportunity as a therapeutic target in cancer and autoimmune disease. Expert Opin Ther Targets. 2011;15 (3):237–251.
51.
ZhengYXYangMRongTTCD74 and macrophage migration inhibitory factor as therapeutic targets in gastric cancer. World J Gastroenterol. 2012;18 (18):2253–2261.
52.
ChengSPLiuCLChenMJCD74 expression and its therapeutic potential in thyroid carcinoma. Endocr Relat Cancer. 2015;22 (2):179–190.
53.
HillmanGGKallinterisNLLiJGenerating MHC Class II+/Ii- phenotype after adenoviral delivery of both an expressible gene for MHC Class II inducer and an antisense Ii-RNA construct in tumor cells. Gene Ther. 2003;10 (17):1512–1518.
54.
LuXKallinterisNLLiJTumor immunotherapy by converting tumor cells to MHC class II-positive, Ii protein-negative phenotype. Cancer Immunol Immunother. 2003;52 (10):592–598.
