Clinical Research
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Meme Kanserlerinde ETS-İlişkili Genin (ERG) Prognostik Önemi

Year 2022, Volume: 1 Issue: 2, 95 - 99, 27.09.2022

Abstract

Amaç: Meme kanseri tüm dünyada kadınlarda en sık görülen kanserdir. Meme kanserinin gelişimi hormonal etkiler, yaşlılık, alkol alımı, obezite, diyet ve genetik değişiklikler gibi birçok faktör tarafından düzenlenmektedir. ETS ile ilgili gen (ERG), ETS ailesinin bir üyesini kodlar. ETS proteinleri, çeşitli biyolojik süreçler tarafından düzenlenen çoklu genlerin ekspresyonunu aktive eden veya baskılayan transkripsiyon faktörleridir. Bu çalışmanın amacı, ERG proteininin günümüzdeki önemini ve meme kanseri etiyolojisindeki rolünü açıklığa kavuşturmaktır.
Gereç ve Yöntemler: 287 primer meme kanseri vakasından alınan doku örneklerinde immünohistokimyasal boyama ile ERG protein ekspresyonunu inceledik.
Bulgular: ERG proteini normal olarak vasküler endotelde eksprese edilmekteydi. Tümör ERG boyaması olguların %27,2'sinde (78/287) pozitif olarak tanımlandı. ERG ekspresyonu ile tümör invazyonu, lenf nodu ve/ veya uzak metastaz varlığı, ileri tümör evresi, histopatolojik derecelendirme ve lenfatik/nöral invazyon gibi klinikopatolojik özellikler arasında istatistiksel olarak anlamlı farklılıklar gözlenmedi. Aksine, ERG ekspresyonu ile hem lenf nodu metastazı hem de Ki-67 indeksi arasında istatistiksel bir ilişki vardı. İlginç bir şekilde, ERG ekspresyonu ile lenf nodu metastazı arasında negatif bir korelasyon bulundu (p<0.01). ERG negatif hastalarda Ki67 yüzdeleri daha yüksek bulunsa da fark istatistiksel olarak anlamlı değildi (p=0.076).
Sonuç: Meme kanserlerinde ERT ekspresyonu, çoğu histolojik prognostik gösterge ile ilişkili değildir. Bununla birlikte, en invaziv ve proliferatif tümörlerin ERG-negatif grupta olduğuna dair bulgularımız, ERG'nin meme kanserlerinde negatif bir prognostik belirteç olarak kullanılabileceği kuşkusu yaratmıştır.

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Thanks

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References

  • 1.Switzer CH, Cheng RYS, Ridnour LA, Glynn SA, Ambs S, Wink DA. Ets-1 is a transcriptional mediator of oncogenic nitric oxide signaling in estrogen receptor-negative breast cancer. Breast Cancer Research 2021: 14: R125.
  • 2.Meadows SM, Myers CT, Krieg PA. Regulation of endothelial cell development by ETS transcription factors. Semin Cell Dev Biol. 2011; 22:976-84.
  • 3.Sood AK, Geradts J, Young J. Prostate-derived ETS factor, an oncogenic driver in breast cancer. Tumor Biolology. 2017;5:1-6.
  • 4.Birol IE, Bahadir B, Ozdamar SO, Kaymaz E, Girgin R. Immunohistochemical expression of the ERG gene in prostatic adenocarcinoma and its relationship with clinicopathological parameters. Malays J Pathol. 2021;43:381 –8.
  • 5.Birdsey GM, Dryden NH, Amsellem V, Gebhardt F, Sahnan K, Haskard DO et al. Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin. Blood 2008;111:3498-506.
  • 6.Vijayaraj P, Le Bras A, Mitchell N, Kondo M, Juliao S, Wasserman M et al. Erg is a crucial regulator of endocardial- mesenchymal transformation during cardiac valve morphogenesis. Development 2012;139: 3973-85.
  • 7.Maroulakou IG, Bowe DB. Expression and function of Ets transcription factors in mammalian development: a regulatory network Oncogene 2000;19:6432-42.
  • 8.Seth A, Watson DK. ETS transcription factors and their emerging roles in human cancer. Eur J Cancer 2005;41:2462-78.
  • 9.Blee AM, Huang H. ERG-mediated cell invasion: a link between development and tumorigenesis. Med Epigenet 2015;3:19-29.
  • 10.Uncel M, Diniz G, Akoz G, Ekin ZY, Sayhan S, Yardım S et al. Loss of nuclear ARID-1A expressions is associated with hormone receptor status in breast cancers. Eur J Breast Health 2019;15:125-9.
  • 11.Eliyatkin N, Aktas S, Diniz G, Ozgur HH, Ekin ZY, Kupelioglu A. Expression of stromal caveolin- 1 may be a predictor for aggressive behaviour of breast cancer. Pathol Oncol Res. 2018;24:59-65.
  • 12.Akoz G, Diniz G, Ekmekci S, Ekin ZY, Uncel M. Evaluation of human epididymal secretory protein 4 expression according to the molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2-positive, triple-negative) of breast cancer. Indian J Pathol Microbiol. 2018;61:323-9.
  • 14.Qi Wu, Juanjuan Li, Si Sun, Shan Zhu, Chuang Chen, Juan Wu et al. Breast carcinoma in situ: An observational study of tumor subtype, treatment and outcomes. Oncotarget. 2017;8:2361–71.
  • 15.Borgquist S, Zhou W, Jirström K, Amini RM, Sollie T, Sørlie T et al. The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study. BMC Cancer 2015;15:468.
  • 16.Van Seijen M, Lips EH, Thompson AM, Nik-Zainal S, Futreal A, Hwang ES et al. Ductal carcinoma in situ: to treat or not to treat, that is the question. Br J Cancer. 2019;121:285–92.
  • 17.Galang, CK, Muller, WJ, Foos, G. Changes in the expression of many Ets family transcription factors and of potential target genes in normal mammary tissue and tumors. J Biol Chem. 2004;279:11281–92.
  • 18.Turner, DP, Moussa, O, Sauane, M. Prostate-derived ETS factor is a mediator of metastatic potential through the inhibition of migration and invasion in breast cancer. Cancer Res. 2007;67:1618–25.
  • 19.Sayhan S, Diniz G, Birol IE, Solakoglu Kahraman D, Calik B. Tissue expression of ETS-related gene in gastric carcinomas. Forbes J Med. 2020;1:90-5.
  • 20.Mahajan, N . Signatures of prostate-derived Ets factor (PDEF) in cancer. Tumour Biol. 2016;37:14335–40.
  • 21.Hägglöf C, Hammarsten P, Strömvall K, Egevad L, Josefsson A, Stattin P et al. TMPRSS2-ERG expression predicts prostate cancer survival and associates with stromal biomarkers. PLoS One 2014;9:e86824.
  • 22.Hoogland AM, Jenster G, Van Weerden WM, Trapman J, van der Kwast T, Roobol MJ et al. ERG immunohistochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer. Mod Pathol. 2012;25:471-9.
  • 23.Hashmi AA, Khan EY, Irfan M, Ali R, Asif H, Naeem M et al. ERG oncoprotein expression in prostatic acinar adenocarcinoma; clinicopathologic significance. BMC Res Notes. 2019;12:35.
  • 13.Diniz G, Irkkan C, Kelten C, Özekinci S. Clues and pitfalls on HER2 evaluation. TERH. 2015;25:2-7.
  • 24.Navaei AH, Walter BA, Moreno V, Pack SD, Pinto P, Merino MJ. Correlation between erg fusion protein and androgen receptor expression by immunohistochemistry in prostate, possible role in diagnosis and therapy. J Cancer. 2017;8:2604-13.
  • 25.Font-Tello A, Juanpere N, De Muga S, Lorenzo M, Lorente JA, Fumado L et al. Association of ERG and TMPRSS2-ERG with grade, stage, and prognosis of prostate cancer is dependent on their expression levels. The Prostate 2015;75:1216-26.
  • 26.Sood AK, Wang J, Mhawech-Fauceglia P. Sam-pointed domain containing ETS transcription factor in luminal breast cancer pathogenesis. Cancer Epidemiol Biomarkers Prev. 2009;18:1899-903.
  • 27.Marcotte R, Sayad A, Brown KR. Functional genomic landscape of human breast cancer drivers, vulnerabilities, and resistance. Cell 2016;164:293-309.
  • 28.Mitas, M, Mikhitarian, K, Hoover, L. Prostate-specific Ets (PSE) factor: a novel marker for detection of metastatic breast cancer in axillary lymph nodes. Br J Cancer. 2002;86:899-904.
  • 29.Diniz G, Birol IE, Oniz H, Vergin C, Aktas S. Evaluation of Immunhistochemical ERG Tissue Expression in Wilms Tumor. BUCHD 2020;10:65-70.
  • 30.Verschoor ML, Verschoor CP, Singh G. Ets-1 global gene expression profile reveals associations with metabolism and oxidative stress in ovarian and breast cancers. Cancer Metab. 2013;1:17.
  • 31.Nazir SU, Kumar K, Afroze D, Rasool I, Bondhopadhyay B, Singh A et al. Differential expression of Ets-1 in breast cancer among North Indian population. J Cell Biochem 2019;120:14552-61.
Year 2022, Volume: 1 Issue: 2, 95 - 99, 27.09.2022

Abstract

Project Number

-

References

  • 1.Switzer CH, Cheng RYS, Ridnour LA, Glynn SA, Ambs S, Wink DA. Ets-1 is a transcriptional mediator of oncogenic nitric oxide signaling in estrogen receptor-negative breast cancer. Breast Cancer Research 2021: 14: R125.
  • 2.Meadows SM, Myers CT, Krieg PA. Regulation of endothelial cell development by ETS transcription factors. Semin Cell Dev Biol. 2011; 22:976-84.
  • 3.Sood AK, Geradts J, Young J. Prostate-derived ETS factor, an oncogenic driver in breast cancer. Tumor Biolology. 2017;5:1-6.
  • 4.Birol IE, Bahadir B, Ozdamar SO, Kaymaz E, Girgin R. Immunohistochemical expression of the ERG gene in prostatic adenocarcinoma and its relationship with clinicopathological parameters. Malays J Pathol. 2021;43:381 –8.
  • 5.Birdsey GM, Dryden NH, Amsellem V, Gebhardt F, Sahnan K, Haskard DO et al. Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin. Blood 2008;111:3498-506.
  • 6.Vijayaraj P, Le Bras A, Mitchell N, Kondo M, Juliao S, Wasserman M et al. Erg is a crucial regulator of endocardial- mesenchymal transformation during cardiac valve morphogenesis. Development 2012;139: 3973-85.
  • 7.Maroulakou IG, Bowe DB. Expression and function of Ets transcription factors in mammalian development: a regulatory network Oncogene 2000;19:6432-42.
  • 8.Seth A, Watson DK. ETS transcription factors and their emerging roles in human cancer. Eur J Cancer 2005;41:2462-78.
  • 9.Blee AM, Huang H. ERG-mediated cell invasion: a link between development and tumorigenesis. Med Epigenet 2015;3:19-29.
  • 10.Uncel M, Diniz G, Akoz G, Ekin ZY, Sayhan S, Yardım S et al. Loss of nuclear ARID-1A expressions is associated with hormone receptor status in breast cancers. Eur J Breast Health 2019;15:125-9.
  • 11.Eliyatkin N, Aktas S, Diniz G, Ozgur HH, Ekin ZY, Kupelioglu A. Expression of stromal caveolin- 1 may be a predictor for aggressive behaviour of breast cancer. Pathol Oncol Res. 2018;24:59-65.
  • 12.Akoz G, Diniz G, Ekmekci S, Ekin ZY, Uncel M. Evaluation of human epididymal secretory protein 4 expression according to the molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2-positive, triple-negative) of breast cancer. Indian J Pathol Microbiol. 2018;61:323-9.
  • 14.Qi Wu, Juanjuan Li, Si Sun, Shan Zhu, Chuang Chen, Juan Wu et al. Breast carcinoma in situ: An observational study of tumor subtype, treatment and outcomes. Oncotarget. 2017;8:2361–71.
  • 15.Borgquist S, Zhou W, Jirström K, Amini RM, Sollie T, Sørlie T et al. The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study. BMC Cancer 2015;15:468.
  • 16.Van Seijen M, Lips EH, Thompson AM, Nik-Zainal S, Futreal A, Hwang ES et al. Ductal carcinoma in situ: to treat or not to treat, that is the question. Br J Cancer. 2019;121:285–92.
  • 17.Galang, CK, Muller, WJ, Foos, G. Changes in the expression of many Ets family transcription factors and of potential target genes in normal mammary tissue and tumors. J Biol Chem. 2004;279:11281–92.
  • 18.Turner, DP, Moussa, O, Sauane, M. Prostate-derived ETS factor is a mediator of metastatic potential through the inhibition of migration and invasion in breast cancer. Cancer Res. 2007;67:1618–25.
  • 19.Sayhan S, Diniz G, Birol IE, Solakoglu Kahraman D, Calik B. Tissue expression of ETS-related gene in gastric carcinomas. Forbes J Med. 2020;1:90-5.
  • 20.Mahajan, N . Signatures of prostate-derived Ets factor (PDEF) in cancer. Tumour Biol. 2016;37:14335–40.
  • 21.Hägglöf C, Hammarsten P, Strömvall K, Egevad L, Josefsson A, Stattin P et al. TMPRSS2-ERG expression predicts prostate cancer survival and associates with stromal biomarkers. PLoS One 2014;9:e86824.
  • 22.Hoogland AM, Jenster G, Van Weerden WM, Trapman J, van der Kwast T, Roobol MJ et al. ERG immunohistochemistry is not predictive for PSA recurrence, local recurrence or overall survival after radical prostatectomy for prostate cancer. Mod Pathol. 2012;25:471-9.
  • 23.Hashmi AA, Khan EY, Irfan M, Ali R, Asif H, Naeem M et al. ERG oncoprotein expression in prostatic acinar adenocarcinoma; clinicopathologic significance. BMC Res Notes. 2019;12:35.
  • 13.Diniz G, Irkkan C, Kelten C, Özekinci S. Clues and pitfalls on HER2 evaluation. TERH. 2015;25:2-7.
  • 24.Navaei AH, Walter BA, Moreno V, Pack SD, Pinto P, Merino MJ. Correlation between erg fusion protein and androgen receptor expression by immunohistochemistry in prostate, possible role in diagnosis and therapy. J Cancer. 2017;8:2604-13.
  • 25.Font-Tello A, Juanpere N, De Muga S, Lorenzo M, Lorente JA, Fumado L et al. Association of ERG and TMPRSS2-ERG with grade, stage, and prognosis of prostate cancer is dependent on their expression levels. The Prostate 2015;75:1216-26.
  • 26.Sood AK, Wang J, Mhawech-Fauceglia P. Sam-pointed domain containing ETS transcription factor in luminal breast cancer pathogenesis. Cancer Epidemiol Biomarkers Prev. 2009;18:1899-903.
  • 27.Marcotte R, Sayad A, Brown KR. Functional genomic landscape of human breast cancer drivers, vulnerabilities, and resistance. Cell 2016;164:293-309.
  • 28.Mitas, M, Mikhitarian, K, Hoover, L. Prostate-specific Ets (PSE) factor: a novel marker for detection of metastatic breast cancer in axillary lymph nodes. Br J Cancer. 2002;86:899-904.
  • 29.Diniz G, Birol IE, Oniz H, Vergin C, Aktas S. Evaluation of Immunhistochemical ERG Tissue Expression in Wilms Tumor. BUCHD 2020;10:65-70.
  • 30.Verschoor ML, Verschoor CP, Singh G. Ets-1 global gene expression profile reveals associations with metabolism and oxidative stress in ovarian and breast cancers. Cancer Metab. 2013;1:17.
  • 31.Nazir SU, Kumar K, Afroze D, Rasool I, Bondhopadhyay B, Singh A et al. Differential expression of Ets-1 in breast cancer among North Indian population. J Cell Biochem 2019;120:14552-61.
There are 31 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Articles
Authors

Gulden Diniz 0000-0003-1512-7584

İsmail Eren Birol 0000-0002-1563-9187

Tekincan Çağrı Aktaş 0000-0002-4960-5225

Dudu Solakoğlu Kahraman 0000-0002-4126-5326

Cem Karaali 0000-0003-2743-7360

Pınar Ayvat 0000-0002-9941-3109

Project Number -
Publication Date September 27, 2022
Submission Date July 6, 2022
Published in Issue Year 2022 Volume: 1 Issue: 2

Cite

APA Diniz, G., Birol, İ. E., Aktaş, T. Ç., Solakoğlu Kahraman, D., et al. (2022). Meme Kanserlerinde ETS-İlişkili Genin (ERG) Prognostik Önemi. İzmir Tıp Fakültesi Dergisi, 1(2), 95-99.
AMA Diniz G, Birol İE, Aktaş TÇ, Solakoğlu Kahraman D, Karaali C, Ayvat P. Meme Kanserlerinde ETS-İlişkili Genin (ERG) Prognostik Önemi. İzmir Tıp Fak. Derg. September 2022;1(2):95-99.
Chicago Diniz, Gulden, İsmail Eren Birol, Tekincan Çağrı Aktaş, Dudu Solakoğlu Kahraman, Cem Karaali, and Pınar Ayvat. “Meme Kanserlerinde ETS-İlişkili Genin (ERG) Prognostik Önemi”. İzmir Tıp Fakültesi Dergisi 1, no. 2 (September 2022): 95-99.
EndNote Diniz G, Birol İE, Aktaş TÇ, Solakoğlu Kahraman D, Karaali C, Ayvat P (September 1, 2022) Meme Kanserlerinde ETS-İlişkili Genin (ERG) Prognostik Önemi. İzmir Tıp Fakültesi Dergisi 1 2 95–99.
IEEE G. Diniz, İ. E. Birol, T. Ç. Aktaş, D. Solakoğlu Kahraman, C. Karaali, and P. Ayvat, “Meme Kanserlerinde ETS-İlişkili Genin (ERG) Prognostik Önemi”, İzmir Tıp Fak. Derg., vol. 1, no. 2, pp. 95–99, 2022.
ISNAD Diniz, Gulden et al. “Meme Kanserlerinde ETS-İlişkili Genin (ERG) Prognostik Önemi”. İzmir Tıp Fakültesi Dergisi 1/2 (September 2022), 95-99.
JAMA Diniz G, Birol İE, Aktaş TÇ, Solakoğlu Kahraman D, Karaali C, Ayvat P. Meme Kanserlerinde ETS-İlişkili Genin (ERG) Prognostik Önemi. İzmir Tıp Fak. Derg. 2022;1:95–99.
MLA Diniz, Gulden et al. “Meme Kanserlerinde ETS-İlişkili Genin (ERG) Prognostik Önemi”. İzmir Tıp Fakültesi Dergisi, vol. 1, no. 2, 2022, pp. 95-99.
Vancouver Diniz G, Birol İE, Aktaş TÇ, Solakoğlu Kahraman D, Karaali C, Ayvat P. Meme Kanserlerinde ETS-İlişkili Genin (ERG) Prognostik Önemi. İzmir Tıp Fak. Derg. 2022;1(2):95-9.