#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Imunohistochemická analýza CD9, CD29 a epitelo-mezenchymové tranzice u triple-negativního karcinomu prsu


Authors: R.- Ondruššek 1 3;  S. Brychtová 1;  M. Bezděková 1;  K. Bouchalova 4;  Z. Vávrová 5;  K. Souček 6;  J. Bouchal 1
Authors‘ workplace: Department of Clinical and Molecular Pathology, Palacký University and University Hospital Olomouc, Czech Republic 1;  EUC Laboratoře CGB a. s. Ostrava, Czech Republic 2;  Department of Molecular and Clinical Pathology and Medical Genetics, University Hospital Ostrava, Czech Republic. 3;  Department of Pediatrics, Palacký University and University Hospital Olomouc, Czech Republic 4;  Department of Surgery, AGEL Hospital Ostrava-Vítkovice, Czech Republic 5;  Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic, † Deceased 6
Published in: Klin Onkol 2024; 38(1): 50-56
Category: Original Articles
doi: https://doi.org/10.48095/ccko202450

Overview

Východiska: Triple-negativní karcinomy prsu (TNBC) jsou heterogenní skupinou nádorů s převážně agresivním chováním a špatnou prognózou. V souvislosti s jejich agresivním chováním a chemorezistencí vůči léčbě se do popředí dostal koncept epitelo-mezenchymové tranzice (EMT). Proteiny CD9 a CD29 jsou spojeny s EMT a mohou hrát roli v progresi TNBC. Naším cílem bylo prozkoumat asociaci těchto markerů s metastázami do lymfatických uzlin, gradingem tumoru, proliferační aktivitou a přežitím pacientů. Pacienti a metody: Náš soubor tvořilo 66 pacientek s TNBC bez neoadjuvantní terapie ve věku 26–81 let. Patologické stadium nádoru se pohybovalo od pT1b do pT3 a histologický stupeň od II do III podle systému Bloom-Richardson. Imunohistochemické hodnocení exprese CD9, CD29, E-cadherinu, vimentinu, androgenového receptoru a Ki-67 bylo provedeno semikvantitativně pomocí H-skóre. Exprese proteinů byla statisticky hodnocena ve vztahu ke klinicko-patologickým parametrům a přežití pacientů. Výsledky: Pozorovali jsme nižší expresi CD9 v metastázách lymfatických uzlin ve srovnání s primárním nádorem (p = 0,021). Exprese CD29 v primárním nádoru byla signifikantně nižší u pacientů s metastázami v lymfatických uzlinách ve srovnání s pacienty bez diseminace (p = 0,03). Ani exprese CD9 ani CD29 proteinu nebyla spojena s přežitím specifickým pro karcinom prsu (BCSS). Nižší exprese E-cadherinu na periferii primárního tumoru byla spojena s horším BCSS (p = 0,038). Pro grading ani přítomnost metastáz v lymfatických uzlinách nebyl nalezen signifikantní vztah s BCSS. Nižší exprese E-cadherinu na periferii byla také spojena s vyšší hladinou Ki67 (Rs −0,26) a vimentinu (Rs −0,33). Závěr: Snížená exprese proteinů CD9 a CD29 byla spojena s růstem metastáz v lymfatických uzlinách, avšak jejich souvislost s přežitím nebyla prokázána. Nižší exprese E-cadherinu na periferii primárního nádoru byla spojena s vysokou proliferací a špatným nádorově specifickým přežitím.

Klíčová slova:

triple-negativní karcinom prsu – CD9 – CD29 – E-cadherin – epitelo-mezenchymová tranzice


Sources

1. Bray F, Ferlay J, Soerjomataram I et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394–424. doi: 10.3322/ caac.21492.

2. Kvokačková B, Remšík J, Jolly MK et al. Phenotypic heterogeneity of triple-negative breast cancer mediated by epithelial-mesenchymal plasticity. Cancers (Basel) 2021; 13(9): 2188. doi: 10.3390/ cancers13092188.

3. Allison KH, Brogi E, Ellis IO et al. Invasive breast carcinoma: general overview. In: Allison KH, Brogi E, Ellis IO
et al. WHO Classification of Tumours. Breast tumours 5th Edition. Lyon: International Agency for Research on Cancer 2019: 82–101.

4. Bauer KR, Brown M, Cress RD et al. 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 2007; 109(9): 1721–1728. doi: 10.1002/ cncr.22618.

5. Blows FM, Driver KE, Schmidt MK et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med 2010; 7(5): e1000279. doi: 10.1371/ journal.pmed.1000279.

6. Liedtke C, Mazouni C, Hess KR et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 2008; 26(8): 1275–1281. doi: 10.1200/ JCO.2007.14.4147.

7. Ekström K, Crescitelli R, Pétursson HI et al. Characterization of surface markers on extracellular vesicles isolated from lymphatic exudate from patients with breast cancer. BMC Cancer 2022; 22(1): 50. doi: 10.1186/ s12885-021-08870-w.

8. Yoshioka Y, Konishi Y, Kosaka N et al. Comparative marker analysis of extracellular vesicles in different human cancer types. J Extracell Vesicles 2013; 2: 20424. doi: 10.3402/ jev.v2i0.20424.

9. Ondruššek R, Kvokačková B, Kryštofová K et al. Prognostic value and multifaceted roles of tetraspanin CD9 in cancer. Front Oncol 2023; 13: 1140738. doi: 10.3389/ fonc.2023.1140738.

10. Geng S, Guo Y, Wang Q et al. Cancer stem-like cells enriched with CD29 and CD44 markers exhibit molecular characteristics with epithelial-mesenchymal transition in squamous cell carcinoma. Arch Dermatol Res 2013; 305(1): 35–47. doi: 10.1007/ s00403-012-1260-2.

11. Clark EA, Brugge JS, Juliano RL et al. Signal transduction from the extracellular matrix. J Cell Biol 1993; 120(3): 577–585. doi: 10.1083/ jcb.120.3.577.

12. Clark EA, Brugge JS. Integrins and signal transduction pathways: the road taken. Science 1995; 268(5208):
233–239. doi: 10.1126/ science.7716514.

13. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 2003; 112(12): 1776–1784. doi: 10.1172/ JCI20530.

14. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119(6): 1420–1428. doi: 10.1172/ JCI39104.

15. Kokkinos MI, Wafai R, Wong MK et al. Vimentin and epithelial-mesenchymal transition in human breast cancer – observations in vitro and in vivo. Cells Tissues Organs 2007; 185(1–3): 191–203. doi: 10.1159/ 000101
320.

16. Remšík J, Fedr R, Navrátil J et al. Plasticity and intratumoural heterogeneity of cell surface antigen expression in breast cancer. Br J Cancer 2018; 118(6): 813–819. doi: 10.1038/ bjc.2017.497.

17. Miyake M, Nakano K, Ieki Y et al. Motility related protein 1 (MRP-1/ CD9) expression: inverse correlation with metastases in breast cancer. Cancer Res 1995; 55(18): 4127–4131.

18. Zöller M. Tetraspanins: push and pull in suppressing and promoting metastasis. Nat Rev Cancer 2009; 9(1): 40–55. doi: 10.1038/ nrc2543.

19. Arihiro K, Kaneko M, Fujii S et al. Loss of CD9 with expression of CD31 and VEGF in breast carcinoma, as predictive factors of lymph node metastasis. Breast Cancer 1998; 5(2): 131–138. doi: 10.1007/ BF02966685.

20. Houle CD, Ding X-Y, Foley JF et al. Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression. Gynecol Oncol 2002; 86(1): 69–78. doi: 10.1006/ gyno.2002.
6729.

21. Sauer G, Windisch J, Kurzeder C et al. Progression of cervical carcinomas is associated with down-regulation of CD9 but strong local re-expression at sites of transendothelial invasion. Clin Cancer Res 2003; 9(17):
6426–6431.

22. Mhawech P, Herrmann F, Coassin M et al. Motility-related protein 1 (MRP-1/ CD9) expression in urothelial bladder carcinoma and its relation to tumor recurrence and progression. Cancer 2003; 98(8): 1649–1657. doi: 10.1002/ cncr.11698.

23. Hashida H, Takabayashi A, Tokuhara T et al. Clinical significance of transmembrane 4 superfamily in colon cancer. Br J Cancer 2003; 89(1): 158–167. doi: 10.1038/ sj.bjc.6601015.

24. Amatya VJ, Takeshima Y, Aoe K et al. CD9 expression as a favorable prognostic marker for patients with malignant mesothelioma. Oncol Rep 2013; 29(1): 21–28. doi: 10.3892/ or.2012.2116.

25. Kwon HJ, Choi JE, Kang SH et al. Prognostic significance of CD9 expression differs between tumour cells and stromal immune cells, and depends on the molecular subtype of the invasive breast carcinoma. Histopathology (2017); 70(7): 1155–1165. doi: 10.1111/ his.13184.

26. Kim T, Kim Y, Kwon HJ. Expression of CD9 and CD82 in papillary thyroid microcarcinoma and its prognostic significance. Endokrynol Pol (2019); 70(3): 224–231. doi: 10.5603/ EP.a2019.0009.

27. Lucarini G, Molinelli E, Licini C et al. Tetraspanin CD9 expression predicts sentinel node status in patients with cutaneous melanoma. Int J Mol Sci (2022); 23(9): 4775. doi: 10.3390/ ijms23094775.

28. Gregory CD, Rimmer MP. Extracellular vesicles arising from apoptosis: forms, functions, and applications. J Pathol 2023; 260(5): 592–608. doi: 10.1002/ path.6138.

29. Truong HH, Xiong J, Ghotra VPS et al. Beta1 integrin inhibition elicits a prometastatic switch through the TGFbeta-miR-200-ZEB network in E-cadherin-positive triple-negative breast cancer. Sci Signal 2014; 7(312): ra15. doi: 10.1126/ scisignal.2004751.

30. Yin H-L, Wu C-C, Lin C-H et al. Beta1 integrin as a prognostic and predictive marker in triple-negative breast cancer. Int J Mol Sci 2016; 17(9): 1432. doi: 10.3390/ ijms17091432.

31. Pleiko K, Haugas M, Parfejevs V et al. Targeting triple-negative breast cancer cells with a beta1-integrin binding aptamer. Mol Ther Nucleic Acids 2023; 33: 871–884. doi: 10.1016/ j.omtn.2023.08.015.

32. Zhang W-J, Wang X-H, Gao S-T et al. Tumor-associated macrophages correlate with phenomenon of epithelial-mesenchymal transition and contribute to poor prognosis in triple-negative breast cancer patients. J Surg Res 2018; 222: 93–101. doi: 10.1016/ j.jss.2017.09.035.

33. Tang D, Xu S, Zhang Q et al. The expression and clinical significance of the androgen receptor and E-cadherin in triple-negative breast cancer. Med Oncol 2012; 29(2): 526–533. doi: 10.1007/ s12032-011-9948-2.

34. Kashiwagi S, Yashiro M, Takashima T et al. Significance of E-cadherin expression in triple-negative breast cancer. Br J Cancer 2010; 103(2): 249–255. doi: 10.1038/ sj.bjc.6605735.

35. Kvokačková B, Fedr R, Kužílková D et al. Single-cell protein profiling defines cell populations associated with triple-negative breast cancer aggressiveness. Mol Oncol 2023; 17(6): 1024–1040. doi: 10.1002/ 1878-0261.13365.

Labels
Paediatric clinical oncology Surgery Clinical oncology

Article was published in

Clinical Oncology

Issue 1

2024 Issue 1

Most read in this issue
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#