Sains Malaysiana 48(7)(2019): 1503–1511
http://dx.doi.org/10.17576/jsm-2019-4807-19
The Association of
ICAM-1 Detected by Immunohistochemical Staining with Triple Negative and
Non-Triple Negative Breast Carcinoma
(Perkaitan ICAM-1 Dikesan oleh Pewarnaan Imunohistokimia
dengan Karsinoma Payudara Ganda Tiga Negatif dan Bukan-Ganda Tiga
Negatif)
CHONG CHOI YEN
& SABREENA SAFUAN*
School
of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150, Kubang
Kerian, Kelantan Darul Naim, Malaysia
Received: 29 July
2018/Accepted: 2 May 2019
ABSTRACT
Metastasis of tumour
cell greatly contributes to the cause of mortality. Tumour-associated
macrophage (TAM) and the intercellular adhesion molecule 1 (ICAM-1)
were associated with metastases of breast carcinoma. However, the relationship
between lymphatic vessel densities and invasion with TAM and ICAM-1
remained unclear. The aim of this study was to investigate the relationship of
lymphovascular densities and invasions with patient’s clinicopathological data.
The roles of TAM and ICAM-1 influencing
lymphovascular invasions were also investigated. Haematoxylin and eosin
(H&E) and immunohistochemical (IHC) staining on a consecutive
section of 37 formalin fixed-paraffin embedded (FFPE)
breast invasive carcinoma samples were carried out. The D2-40, CD34, CD163,
and ICAM-1 antibodies were used to stain lymphatic vessel,
blood vessel, TAM, and ICAM-1 receptor, respectively.
The total lymphatic vessel density (LVD) was significantly reduced
on increased tumor size (p=0.045). The increase of
intra-tumoral LVD and lymphatic vessel invasion (LVI)
was significantly associated with human epidermal growth factor receptor 2 (HER2)
negative status (p=0.022 and p=0.05, respectively). The percentage of LVI was
higher than blood vessel invasion (BVI) in 18.5%. Lymphovascular
invasions detected in H&E were missed in 49.76% compared with those
detected in IHC-stained tissues (206/410). ICAM-1
scores were significantly associated with non-triple negative breast cancer
(non-TNBC) (p=0.008). ICAM-1 is significantly
overexpressed on non-TNBC sample. Therefore, ICAM-1
might be clinically useful as a targeted molecule for non-TNBC patients.
In histological reporting, in addition to H&E staining, IHC staining
using D2-40 and CD34 should be considered to increase
the accuracy of diagnosis.
Keywords: Breast
carcinoma; CD34; D2-40; ICAM-1; lymphovascular invasion
ABSTRAK
Metastasis sel tumor menyumbang
kepada mortaliti. Makrofaj berkaitan tumor (TAM)
dan molekul lekatan antara sel 1 (ICAM-1) dikaitkan dengan metastasis
karsinoma payudara. Walau bagaimanapun, hubungan antara ketumpatan
dan pencerobohan saluran limfa oleh TAM dan ICAM-1
masih tidak jelas. Tujuan kajian ini adalah untuk mengkaji hubungan
antara ketumpatan dan pencerobohan limfovaskular dengan data klinikopatologi
pesakit. Peranan TAM dan ICAM-1 yang mempengaruhi pencerobohan
limfovaskular juga dikaji. Pewarnaan hematoksilin dan eosin (H&E)
dan imunohistokimia (IHC) pada hirisan berterusan 37
sampel awetan formalin dan benaman parafin (FFPE)
karsinoma invasif payudara telah dijalankan. Antibodi D2-40, CD34,
CD163,
dan ICAM-1 masing-masing digunakan untuk mewarna saluran limfa,
saluran darah, TAM, dan reseptor ICAM-1.
Ketumpatan saluran limfatik (LVD) berkurangan dengan ketara
pada saiz tumor yang meningkat (p=0.045). Peningkatan LVD
dan pencerobohan saluran limfatik (LVI) intra-tumoral berkait dengan
reseptor faktor pertumbuhan epidermis manusia 2 (HER2)
negatif (p=0.022 dan p=0.05). Peratusan LVI adalah
lebih tinggi daripada pencerobohan saluran darah (BVI)
pada 18.5%. Pencerobohan limfovaskular yang dikesan dalam H&E
adalah 49.76% berbanding yang dikesan dalam tisu yang diwarnakan
dengan IHC (206/410).
Skor ICAM-1 adalah berkaitan secara signifikan dengan kanser
payudara bukan tiga negatif (bukan-TNBC) (p=0.008). ICAM-1
secara signifikan meningkat pada sampel bukan-TNBC.
Oleh itu, ICAM-1 mungkin berguna secara klinikal sebagai molekul sasaran
untuk merawat pesakit bukan-TNBC. Dalam laporan histologi,
sebagai tambahan kepada pewarnaan H&E, pewarnaan IHC menggunakan
D2-40 dan CD34 perlu dipertimbangkan untuk meningkatkan ketepatan
diagnosis.
Kata kunci: CD34; D2-40; ICAM-1; karsinoma payudara; pencerobohan
limfovaskular
REFERENCES
Abduelkarem, A.R., Saif, F.K., Saif, S. & Alshoaiby, T.A.
2015. Evaluation of breast cancer awareness among female university students in
university of Sharjah, UAE. Advances in Breast Cancer Research 04(01):
9-21.
Addis, M.F., Tanca, A., Pagnozzi, D., Crobu, S., Fanciulli, G.,
Cossu‐Rocca, P. & Uzzau, S. 2009. Generation of high‐quality
protein extracts from formalin‐fixed, paraffin‐embedded tissues. Proteomics 9(15): 3815-3823.
Bono, P., Wasenius, V.M., Heikkilä, P., Lundin, J., Jackson, D.G.
& Joensuu, H. 2004. High LYVE-1-positive lymphatic vessel numbers are
associated with poor outcome in breast cancer. Clinical Cancer Research 10(21):
7144-7149.
Braun, M., Flucke, U., Debald, M., Walgenbach-Bruenagel, G.,
Walgenbach, K.J., Höller, T., Pölcher, M., Wolfgarten, M., Sauerwald, A. &
Keyver-Paik, M. 2008. Detection of lymphovascular invasion in early breast
cancer by D2-40 (podoplanin): A clinically useful predictor for axillary lymph
node metastases. Breast Cancer Research and Treatment 112(3): 503-511.
Drivalos, A., Papatsoris, A.G., Chrisofos, M., Efstathiou, E.
& Dimopoulos, M.A. 2011. The role of the cell adhesion molecules
(integrins/cadherins) in prostate cancer. International Braz. J. Urol. 37(3):
302-306.
Espina, V., Mehta, A.I., Winters, M.E., Calvert, V., Wulfkuhle,
J., Petricoin, E.F. & Liotta, L. A. 2003. Protein microarrays: Molecular
profiling technologies for clinical specimens. Proteomics 3(11):
2091-2100.
Farahani, E., Patra, H.K., Jangamreddy, J.R., Rashedi, I.,
Kawalec, M., Rao Pariti, R.K., Batakis, P. & Wiechec, E. 2014. Cell
adhesion molecules and their relation to (cancer) cell stemness. Carcinogenesis 35(4): 747-759.
Goddard, J., Sutton, C., Berry, D., O’Byrne, K.J. &
Kockelbergh, R. 2001. The use of microvessel density in assessing human
urological tumours. BJU International 87(9): 866-875.
Guo, P., Huang, J., Wang, L., Jia, D., Yang, J., Dillon, D.A.,
Zurakowski, D., Mao, H., Moses, M.A. & Auguste, D.T. 2014. ICAM-1 as a
molecular target for triple negative breast cancer. Proceedings of the
National Academy of Sciences 111(41): 14710-14715.
Hein, S., Müller, V., Köhler, N., Wikman, H., Krenkel, S.,
Streichert, T., Schweizer, M., Riethdorf, S., Assmann, V. & Ihnen, M. 2011.
Biologic role of activated leukocyte cell adhesion molecule overexpression in
breast cancer cell lines and clinical tumor tissue. Breast Cancer Research
and Treatment 129(2): 347-360.
Hua, S. 2013. Targeting sites of inflammation: Intercellular
adhesion molecule-1 as a target for novel inflammatory therapies. Frontiers
in Pharmacology 4: 127.
Hudis, C.A. 2007. Trastuzumab-mechanism of action and use in
clinical practice. New England Journal of Medicine 357(1): 39-51.
Kammerer, S., Roth,
R.B., Reneland, R., Marnellos, G., Hoyal, C.R., Markward, N.J., Ebner, F.,
Kiechle, M., Schwarz- Boeger, U., Griffiths, L.R., Ulbrich, C., Chrobok, K.,
Forster, G., Praetorius, G.M., Meyer, P., Rehbock, J., Cantor, C.R., Nelson,
M.R. & Braun, A. 2004. Large-scale association study identifies ICAM gene
region as breast and prostate cancer susceptibility locus. Cancer Res. 64(24):
8906-8910.
Kozłowski, L.,
Zakrzewska, I., Tokajuk, P. & Wojtukiewicz, M. 2002. Concentration of
interleukin-6 (IL-6), interleukin-8 (IL-8) and interleukin-10 (IL-10) in blood
serum of breast cancer patients. Roczniki Akademii Medycznej w Bialymstoku 48:
82-84.
Lachapelle,
J. & Foulkes, W. 2011. Triple-negative and basal-like breast cancer: Implications
for oncologists. Current Oncology 18(4): 161-164.
Ley,
K., Miller, Y.I. & Hedrick, C.C. 2011. Monocyte and macrophage dynamics
during atherogenesis. Arteriosclerosis, Thrombosis, and Vascular Biology 31(7):
1506-1516.
Maksoud,
N.A.E., Ragab, H.M., Shaaban, H.M., Radwan, S.M., Elaziz, W.A. & Hafez,
N.H. 2017. Potential value of ICAM- 1 as a biomarker for detection of
progression and prognosis in breast carcinoma. American Journal of
Biochemistry and Molecular Biology 7(2): 91-95.
Martinez,
F.O., Sica, A., Mantovani, A. & Locati, M. 2008. Macrophage activation and
polarization. Frontiers in Bioscience: A Journal and Virtual Library 13:
453-461.
Meric-Bernstam,
F. & Hung, M.C. 2006. Advances in targeting human epidermal growth factor
receptor-2 signaling for cancer therapy. Clinical Cancer Research 12(21):
6326-6330.
Minn,
A.J., Gupta, G.P., Siegel, P.M., Bos, P.D., Shu, W., Giri, D.D., Viale, A.,
Olshen, A.B., Gerald, W.L. & Massagué, J. 2005. Genes that mediate breast
cancer metastasis to lung. Nature 436(7050): 518-524.
Mitri,
Z., Constantine, T. & O’Regan, R. 2012. The HER2 receptor in breast cancer:
Pathophysiology, clinical use, and new advances in therapy. Chemother. Res.
Pract. 2012: 743193.
Mohammed,
R.A., Ellis, I.O., Mahmmod, A.M., Hawkes, E.C., Green, A.R., Rakha, E.A. &
Martin, S.G. 2011. Lymphatic and blood vessels in basal and triple-negative
breast cancers: Characteristics and prognostic significance. Modern
Pathology 24(6): 774-785.
Mohammed,
R.A., Martin, S.G., Gill, M.S., Green, A.R., Paish, E.C. & Ellis, I.O.
2007. Improved methods of detection of lymphovascular invasion demonstrate that
it is the predominant method of vascular invasion in breast cancer and has
important clinical consequences. The American Journal of Surgical Pathology 31(12):
1825-1833.
Muro,
S. & Muzykantov, V. 2005. Targeting of antioxidant and anti-thrombotic
drugs to endothelial cell adhesion molecules. Current Pharmaceutical Design 11(18):
2383-2401.
Nishida,
N., Yano, H., Nishida, T., Kamura, T. & Kojiro, M. 2006. Angiogenesis in cancer. Vascular Health And Risk Management 2(3): 213-219.
Obeid,
E., Nanda, R., Fu, Y.X. & Olopade, O.I. 2013. The role of tumor-associated
macrophages in breast cancer progression (review). International Journal of
Oncology 43(1): 5-12.
Okegawa,
T., Pong, R.C., Li, Y. & Hsieh, J.T. 2004. The role of cell adhesion
molecule in cancer progression and its application in cancer therapy. Acta
Biochimica Polonica- English Edition 51: 445-458.
Perou,
C.M., Sørlie, T., Eisen, M.B., van de Rijn, M., Jeffrey, S.S., Rees, C.A.,
Pollack, J.R., Ross, D.T., Johnsen, H. & Akslen, L.A. 2000. Molecular
portraits of human breast tumours. Nature 406(6797): 747-752.
Ran,
S., Volk, L., Hall, K. & Flister, M.J. 2010. Lymphangiogenesis and
lymphatic metastasis in breast cancer. Pathophysiology 17(4): 229-251.
Rodríguez-Pinilla,
S.M., Sarrió, D., Honrado, E., Hardisson, D., Calero, F., Benitez, J. &
Palacios, J. 2006. Prognostic significance of basal-like phenotype and fascin
expression in node-negative invasive breast carcinomas. Clinical Cancer
Research 12(5): 1533-1539.
Rosette,
C., Roth, R.B., Oeth, P., Braun, A., Kammerer, S., Ekblom, J. & Denissenko,
M.F. 2005. Role of ICAM1 in invasion of human breast cancer cells. Carcinogenesis 26(5): 943-950.
Safuan,
S., Storr, S.J., Patel, P.M. & Martin, S.G. 2012. A comparative study of
adhesion of melanoma and breast cancer cells to blood and lymphatic
endothelium. Lymphat. Res. Biol. 10(4): 173-181.
Schoppmann,
S.F., Bayer, G., Aumayr, K., Taucher, S., Geleff, S., Rudas, M., Kubista, E.,
Hausmaninger, H., Samonigg, H., Gnant, M., Jakesz, R. & Horvat, R. 2004.
Prognostic value of lymphangiogenesis and lymphovascular invasion in invasive
breast cancer. Annals of Surgery 240(2): 306-312.
Schroder,
C., Witzel, I., Muller, V., Krenkel, S., Wirtz, R.M., Janicke, F., Schumacher,
U. & Milde-Langosch, K. 2011. Prognostic value of intercellular adhesion
molecule (ICAM)- 1 expression in breast cancer. J. Cancer Res. Clin. Oncol. 137(8):
1193-1201.
Storr,
S.J., Safuan, S., Mitra, A., Elliott, F., Walker, C., Vasko, M.J., Ho, B.,
Cook, M., Mohammed, R.A. & Patel, P.M. 2012. Objective assessment of blood
and lymphatic vessel invasion and association with macrophage infiltration in
cutaneous melanoma. Modern Pathology 25(4): 493-504.
Viale,
G., Zurrida, S., Maiorano, E., Mazzarol, G., Pruneri, G., Paganelli, G.,
Maisonneuve, P. & Veronesi, U. 2005. Predicting the status of axillary
sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated in
a single institution. Cancer 103(3): 492-500.
Vleugel,
M., Bos, R., Van der Groep, P., Greijer, A., Shvarts, A., Stel, H., Van der
Wall, E. & Van Diest, P. 2004. Lack of lymphangiogenesis during breast
carcinogenesis. Journal of Clinical Pathology 57(7): 746-751.
Volodko,
N., Reiner, A., Rudas, M. & Jakesz, R. 1998. Tumour-associated macrophages
in breast cancer and their prognostic correlations. The Breast 7:
99-91-95.
Wolff,
C., Schott, C., Porschewski, P., Reischauer, B. & Becker, K.F. 2011.
Successful protein extraction from over-fixed and long-term stored
formalin-fixed tissues. PLoS ONE 6(1): e16353.
*Corresponding author; email:
sabreena@usm.my
|