Macrophages as independent prognostic factors in small T1 breast cancers

Carrio,Roberto; Koru-Sengul,Tulay; Miao,Feng; Glück,Stefan; Lopez,Omar; Selman,Yamil; Alvarez,Consuelo; Milikowski,Clara; Gomez,Carmen; Jorda,Merce; Nadji,Mehrad; Torroella-Kouri,Marta

doi:10.3892/or.2012.2088

Macrophages as independent prognostic factors in small T1 breast cancers

Authors:
- Roberto Carrio
- Tulay Koru-Sengul
- Feng Miao
- Stefan Glück
- Omar Lopez
- Yamil Selman
- Consuelo Alvarez
- Clara Milikowski
- Carmen Gomez
- Merce Jorda
- Mehrad Nadji
- Marta Torroella-Kouri
View Affiliations

Affiliations: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA, Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, FL 33136, USA, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA, Department of Pathology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Published online on: October 17, 2012 https://doi.org/10.3892/or.2012.2088
Pages: 141-148

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Breast cancer is the second leading cause of death by cancer in women in the United States. The occurrence of high numbers of macrophages in the tumor stroma has been associated with tumor progression and poor prognosis in breast and other solid malignancies. However, macrophage numbers in tumors have not been validated as a prognostic factor in clinical practice. The present analysis was designed as a pilot study aimed at determining whether the presence of CD68+ macrophages is an independent prognostic factor in small T1 estrogen receptor (ER)+ breast cancers across three different ethnic groups, i.e. African-American, Latina and Caucasian women. A retrospective pilot analysis of 30 T1 breast cancer cases encompassing these three ethnic groups was carried out. African-American and Latina women present with less incidence but more aggressive breast cancer disease and, therefore, proportionally higher death rates. Using immunohistochemistry, we sought to identify whether there was any association between the presence and density of CD68+ macrophages and standard prognostic markers with overall survival in these groups. Our data revealed that overall survival did not differ significantly for the occurrence or density of CD68+ macrophages in T1 ER+ tumors. There were also no significant differences in overall survival for the occurrence of CD68+ macrophages across ethnicities, although macrophage numbers were significantly higher in tumors from African-American and Latina than in Caucasian patients. Importantly, but not surprisingly, the absence of the progesterone receptor was associated very strongly with decreased overall survival. This pilot project shows that CD68+ macrophages are not pivotal in determining tumor prognosis in early T1 breast cancers. New studies are presently being conducted to assess the value of different macrophage markers and macrophage activation profiles as prognostic factors in breast cancers of different clinical stages, using a larger number of patients among these three different ethnicities.

View Figures

View References

1	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics. CA Cancer J Clin. 60:277–300. 2010.
2	Karlsson E, Danielsson A, Delle U, et al: Chromosomal changes associated with clinical outcome in lymph node-negative breast cancer. Cancer Genet Cytogenet. 172:139–146. 2007. View Article : Google Scholar : PubMed/NCBI
3	Eng-Wong J and Isaacs C: Prediction of benefit from adjuvant treatment in patients with breast cancer. Clin Breast Cancer. 10(Suppl 1): E32–E37. 2010. View Article : Google Scholar : PubMed/NCBI
4	Oakman C, Bessi S, Zafarana E, et al: Recent advances in systemic therapy: new diagnostics and biological predictors of outcome in early breast cancer. Breast Cancer Res. 11:2052009. View Article : Google Scholar : PubMed/NCBI
5	Marchionni L, Wilson RF, Marinopoulos SS, et al: Impact of gene expression profiling tests on breast cancer outcomes. Evid Rep Technol Assess (Full Rep). 1–105. 2007.PubMed/NCBI
6	Perreard L, Fan C, Quackenbush JF, et al: Classification and risk stratification of invasive breast carcinomas using a real-time quantitative RT-PCR assay. Breast Cancer Res. 8:R232008. View Article : Google Scholar : PubMed/NCBI
7	Sica A, Larghi P, Mancino A, et al: Macrophage polarization in tumour progression. Semin Cancer Biol. 18:349–355. 2008. View Article : Google Scholar : PubMed/NCBI
8	Pollard JW: Macrophages define the invasive microenvironment in breast cancer. J Leukoc Biol. 84:623–630. 2008. View Article : Google Scholar : PubMed/NCBI
9	Qian BZ, Li J, Zhang H, et al: CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 475:222–225. 2011. View Article : Google Scholar : PubMed/NCBI
10	Sica A, Saccani A and Mantovani A: Tumor-associated macrophages: a molecular perspective. Int Immunopharmacol. 2:1045–1054. 2002. View Article : Google Scholar : PubMed/NCBI
11	Leek RD and Harris AL: Tumor-associated macrophages in breast cancer. J Mammary Gland Biol Neoplasia. 7:177–189. 2002. View Article : Google Scholar : PubMed/NCBI
12	Zhang BC, Gao J, Wang J, et al: Tumor-associated macrophages infiltration is associated with peritumoral lymphangiogenesis and poor prognosis in lung adenocarcinoma. Med Oncol. 28:1447–1452. 2011. View Article : Google Scholar : PubMed/NCBI
13	Zhang B, Yao G, Zhang Y, et al: M2-polarized tumor-associated macrophages are associated with poor prognoses resulting from accelerated lymphangiogenesis in lung adenocarcinoma. Clinics (São Paulo). 66:1879–1886. 2011.PubMed/NCBI
14	Chen JJ, Lin YC, Yao PL, et al: Tumor-associated macrophages: the double-edged sword in cancer progression. J Clin Oncol. 23:953–964. 2005. View Article : Google Scholar : PubMed/NCBI
15	Mantovani A, Sica A, Allavena P, Garlanda C and Locati M: Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation. Hum Immunol. 70:325–330. 2009. View Article : Google Scholar : PubMed/NCBI
16	MacMicking J, Xie QW and Nathan C: Nitric oxide and macrophage function. Annu Rev Immunol. 15:323–350. 1997. View Article : Google Scholar : PubMed/NCBI
17	Fedewa SA, Edge SB, Stewart AK, et al: Race and ethnicity are associated with delays in breast cancer treatment (2003–2006). J Health Care Poor Underserved. 22:128–141. 2011.
18	Miranda PY, Tarraf W and Gonzalez HM: Breast cancer screening and ethnicity in the United States: implications for health disparities research. Breast Cancer Res Treat. 128:535–542. 2011. View Article : Google Scholar : PubMed/NCBI
19	Miranda PY, Tarraf W, Gonzalez P, Johnson-Jennings M and Gonzalez HM: Breast cancer screening trends in the United States and ethnicity. Cancer Epidemiol Biomarkers Prev. 21:351–357. 2012. View Article : Google Scholar : PubMed/NCBI
20	McGuire WL, De La Garza M and Chamness GC: Evaluation of estrogen receptor assays in human breast cancer tissue. Cancer Res. 37:637–639. 1977.PubMed/NCBI
21	Bloom HJ and Richardson WW: Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 11:359–377. 1957.PubMed/NCBI
22	Elston CW: The assessment of histological differentiation in breast cancer. Aust NZ J Surg. 54:11–15. 1984. View Article : Google Scholar : PubMed/NCBI
23	Elston CW and Ellis IO: Pathological 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. 19:403–410. 1991. View Article : Google Scholar
24	Berrang TS, Lesperance M, Truong PT, et al: Which prediction models best identify additional axillary disease after a positive sentinel node biopsy for breast cancer? Breast Cancer Res Treat. 133:695–702. 2012. View Article : Google Scholar
25	Arslan AA, Silvera D, Arju R, et al: Atypical ezrin localization as a marker of locally advanced breast cancer. Breast Cancer Res Treat. 134:981–988. 2012. View Article : Google Scholar : PubMed/NCBI
26	Mook S, Knauer M, Bueno-de-Mesquita JM, et al: Metastatic potential of T1 breast cancer can be predicted by the 70-gene MammaPrint signature. Ann Surg Oncol. 17:1406–1413. 2010. View Article : Google Scholar : PubMed/NCBI
27	Reis-Filho JS and Pusztai L: Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet. 378:1812–1823. 2011. View Article : Google Scholar : PubMed/NCBI
28	Raam S, Gelman R, Cohen JL, et al: Estrogen receptor assay: interlaboratory and intralaboratory variations in the measurement of receptors using dextran-coated charcoal technique: a study sponsored by E.C.O.G. Eur J Cancer. 17:643–649. 1981. View Article : Google Scholar
29	Mahmoud SM, Lee AH, Paish EC, et al: Tumour-infiltrating macrophages and clinical outcome in breast cancer. J Clin Pathol. 65:159–163. 2012. View Article : Google Scholar : PubMed/NCBI
30	Shabo I, Stal O, Olsson H, Dore S and Svanvik J: Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival. Int J Cancer. 123:780–786. 2008. View Article : Google Scholar : PubMed/NCBI
31	Lau SK, Chu PG and Weiss LM: CD163: a specific marker of macrophages in paraffin-embedded tissue samples. Am J Clin Pathol. 122:794–801. 2004. View Article : Google Scholar : PubMed/NCBI
32	Brown M, Tsodikov A, Bauer KR, Parise CA and Caggiano V: The role of human epidermal growth factor receptor 2 in the survival of women with estrogen and progesterone receptor-negative, invasive breast cancer: the California Cancer Registry, 1999–2004. Cancer. 112:737–747. 2008.PubMed/NCBI
33	Vona-Davis L and Rose DP: The influence of socioeconomic disparities on breast cancer tumor biology and prognosis: a review. J Womens Health (Larchmt). 18:883–893. 2009. View Article : Google Scholar : PubMed/NCBI
34	Bauer KR, Brown M, Cress RD, Parise CA and Caggiano V: Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California Cancer Registry. Cancer. 109:1721–1728. 2007. View Article : Google Scholar
35	Thakkar JP and Mehta DG: A review of an unfavorable subset of breast cancer: estrogen receptor positive progesterone receptor negative. Oncologist. 16:276–285. 2011. View Article : Google Scholar : PubMed/NCBI
36	Hugh J, Hanson J, Cheang MC, et al: Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol. 27:1168–1176. 2009. View Article : Google Scholar