Kubilay DALCI, Yalçın KEKEÇ, Semra PAYDAŞ, Suzan ZORLUDEMİR, Melek ERGİN, Kahraman TANRIVERDİ, Gülşah SEYDAOĞLU, Gülsüm UÇAR

Meme kanserinde PRAME (preferentially expressed antigen of melanoma) ekspresyonunun prognostik önemi

Amaç: Bu çalışmanın amacı 54 meme kanseri ve 37 iyi huylu meme lezyonu olan hastada PRAME (Preferentially Expressed Antigen of Melanoma) ekspresyonunu tespit etmektir. Gereç ve Yöntem: Reverse transkripsiyon polimeraz zincir reaksiyonu (RT-PCR) ile 54 meme kanseri, 20 benign meme lezyonu ve 10 normal meme dokusu örneğindeki PRAM Eekspresyonu çalışıldı. İmmunohistokimyasal (IHC) yöntem ile PRAME ekspresyonu, 54 meme kanserili hastanın hem tümör hem de normal meme dokusundan ve 37 benign meme lezyonunda çalışıldı. PRAME için RT-PCR ve IHC sonuçları bu çalışmada karşılaştırıldı. Bulgular: Meme kanserinin %50'sinde, benign meme lezyonlarının ise %25'inde PRAME ekspresyonu olduğu saptandı. İnvaziv meme kanseri olan dokularda IHC yöntemi kullanılarak bakılan PRAME ekspresyonunda; (+), (++) ve (+++) boyanma oranları sırasıyla %29,6, %31,5 ve %3,7 oranında bulundu. Hem IHC hem de RT-PCR ile saptanan PRAME ekspresyonu prognostik parametrelerle karşılaştırıldı. Meme kanserinde PRAME ekspresyonunun yüksek grade ve negatif hormon reseptörü ile ilişkili olduğu tespit edildi. RT-PCR ile IHC ile bakılan PRAME sonuçları arasında anlamlı ilişki bulundu. Sonuç: Hem taze dokularda RT-PCR yöntemi, hem de parafin bloklarda IHC yöntemi, meme kanserinde PRAME ekspresyonunu ve PRAME’in prediktif önemini belirlemede kullanılabilir.

Prognostic significance of PRAME (preferentially expressed antigen of melanoma) expression in breast cancer

Purpose: The aim of this study is to detect the PRAME (Preferentially Expressed Antigen of Melanoma) in 54 patients with breast cancer and 37 patients with benign breast lesions. Materials and Methods: PRAME expressions in 54 breast cancer, 20 benign breast lesions and 10 normal breast tissue samples were studied with RT-PCR. Expression of PRAME was studied with IHC in 37 benign breast lesions, in 54 breast cancer patients from both tumor and normal breast tissue. RT-PCR and IHC results for PRAME were compared in this study. Results: PRAME was found to be expressed in 50 % of the breast cancer and 25 % of the benign breast lesions. Using IHC method, (+), (++) and (+++) staining for PRAME expression were found in 29,6%, 31,5% and 3,7% of the cases, respectively in invasive component of the breast cancer. PRAME expression detected by both IHC and RT-PCR was compared with prognostic parameters. PRAME expression in breast cancer was found to be associated with high tumor grade and negative hormone receptor. We found an important association between PRAME RT-PCR and of PRAME IHC. Conclusion: Both RT-PCR in fresh tissues and IHC method in paraffin embedded tissues can be used to identify PRAME expression and the predictive role of PRAME expression.

Keywords:

breast cancer, PRAME, expression,

PDF

___

1. Ikeda H, Lethe B, Lehmann F. Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity. 1997;6:199-208.
2. Li CM, Guo M, Borczuk A. Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition. Am J Pathol. 2002;160:2181-190.
3. Paydas S, Tanrıverdi K, Yavuz S, Seydaoglu G. PRAME mRNA levels in cases with chronic leukemia: clinical importance and review of the literature. Leuk Res. 2007;31:365-9.
4. Paydas S, Tanriverdi K, Yavuz S, Disel U, Baslamisli F, Burgut R. PRAME mRNA levels in cases with acute leukemia: clinical importance and future prospects. J. Hematol. 2005;79:257-61.
5. Neumann E, Engelsberg A, Decker J. Heterogeneous expression of the tumor-associated antigens RAGE1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell-based immunotherapies? Cancer Res. 2006;58:4090-5.
6. Matsushita M, Yamazaki R, Kawakami Y. Matsushita M, Yamazaki R, Kawakami Y. Quantitative analysis of PRAME for detection of minimal residual disease in leukemia. Methods Mol Med. 2004;97:267-75.
7. Oberthuer A, Hero B, Spitz R, Berthold F, Fischer M. The tumor-associated antigen PRAME is universally expressed in high-stage neuroblastoma and associated with poor outcome. Clin Cancer Res. 2004;10:4307‐ 13.
8. Epping MT, Wang L, Edel MJ, Carlee L, Hernandez M, Bernards R. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell. 2005;122:835-47.
9. Epping MT, Bernards R. A causal role for the human tumor antigen preferentially expressed antigen of melanoma in cancer. Cancer Res. 2006;66:10639-42.
10. Tajeddine N, Gala JL, Louis M. Tumor-associated antigen preferentially expressed antigen of melanoma (PRAME) induces caspase independent cell death in vitro and reduces tumorigenicity in vivo. Cancer Res. 2005;65:7348-55.
11. Gollner S, Steinbach D, Schenk T, Gruhn B, Zintl F, Ramsay E. Childhood acute myelogenous leukamia: association between PRAME, apoptosis and MDRreletad gene expression. Eur J Cancer. 2006;42:2807- 14.
12. Santamaría C, Chillón MC, García-Sanz R, Balanzategui A, Sarasquete ME, Alcoceba M et al. The relevance of preferentially expressed antigen of melanoma (PRAME) as a marker of disease activity and prognosis in acute promyelocytic leukemia. Haematologica. 2008;93:1797-805.
13. Doolan P, Clynes M, Kennedy S, Mehta JP, Crown J, O'Driscoll L. Prevalence and prognostic and predictive relevance of PRAME in breast cancer. Breast Cancer Res Treat. 2008;109:359‐65.
14. Epping MT, Hart AA, Glas AM, Krijgsman O, Bernards R. PRAME expression and clinical outcome of breast cancer. Br J Cancer. 2008;99:398-403.
15. Curigliano G, Bagnardi V, Ghioni M, Louahed J, Brichard V, Lehmann FF et al. Expression of tumorassociated antigens in breast cancer subtypes. Breast. 2020;49:202‐9.
16. Sun Z, Wu Z, Zhang F, Guo Q, Li L, Li K et al. PRAME is critical for breast cancer growth and metastasis. Gene. 2016;594:160-4.
17. Siegel RL, Miller KD, Jemal A. Cancer statistics 2020. CA Cancer J Clin. 2020;70:7-30.
18. Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M et al. SEER Cancer Statistics Review. 1975‐ 2016. Bethesda, National Cancer Institute, 2019.
19. Takalkar UV, Advani S. Prognostic indicators in breast cancer patients. J Cancer Res Forecast. 2018;1:1011.
20. Matsushita M, Ikeda H, Kizaki M, S Okamoto, M Ogasawara, Y Ikeda et al. Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. Br J Haematol. 2001;112:916‐26.
21. Al-Khadairi G, Naik A, Thomas R, Al-Sulaiti B, Rizly S, Decock J. PRAME promotes epithelial-tomesenchymal transition in triple negative breast cancer. J Transl Med. 2019;17:9.