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CD44 EXPRESSION IN PROSTATIC ADENOCARCINOMA: CORRELATION WITH GLEASON GRADES

Year 2020, Volume: 22 Issue: 2, 233 - 239, 31.08.2020

Mahi Balcı Gülhan Özdemir

Abstract

Objective: CD44, a cell-surface adhesion protein, is a marker of stem cells and is involved in the structural maintenance of prostate gland basal cells. It plays an important role in prostate carcinogenesis; however, research results till date have been inconsistent. The current study was conducted to evaluate the expression level of CD44 among carcinomas with different Gleason growth patterns and hyperplastic glands.
Material and Methods: Eighty archival tissue samples from patients with either prostate carcinoma of differing Gleason patterns or benign prostate hyperplasia from the pathology archives of the Kırıkkale University, Faculty of Medicine, from 2011 to 2018 were included. Immunoreaction to CD44 antibodies was evaluated by calculating positively stained cell percentage and staining intensity. Mean values and significance were determined using the Kruskal–Wallis test. p<0.05 was considered significant.
Results: CD44 staining was more diffuse and intense in most of benign hyperplastic tissues compared to carcinoma cases (p values ranged from <0.01 to 0.005). Expression level gradually decreased with increasing severity of histologic pattern. Pattern 3 tumor showed higher percentage of positively stained cells than pattern 4 (p<0.01) There was no positivity with CD44 in grade 5 tumours. Also, in pattern 4 only few cells reacted with CD44. There was no statistically significant difference in the staining score between pattern 4 and 5 (p=0.278).
Conclusion: We conclude that once cancerous properties have been established, cells tend to lose the ability of CD44 expression. CD 44 expression in low grade carcinomas suggest that CD 44 maintains the tumor in a differentiated, gland forming state so it may not act as a cancer stem cell marker in prostate carcinogenesis.

Keywords

Prostate Carcinogenesis Stem cells Prostatic Hyperplasia Keratins

References

  • 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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.
  • 2. Crona DJ, Whang Y. Androgen receptor-dependent and -independent mechanisms involved in prostate cancer therapy resistance. Cancers (Basel). 2017;9(6):67.
  • 3. Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. 2018;11(1):64.
  • 4. Harris KS, Kerr BA. Prostate cancer stem cell markers drive progression, therapeutic resistance, and bone metastasis. Stem Cells Int. 2017;(2):1-9.
  • 5. Kalantari E, Asgari M, Nikpanah S, Salarieh N, Asadi Lari MH, Madjd Z. Co-Expression of putative cancer stem cell markers CD44 and CD133 in prostate carcinomas. Pathol Oncol Res. 2017;23(4):793-802.
  • 6. Mizukami T, Kamachi H, Mitsuhashi T, Tsuruga Y, Hatanaka Y, Kamiyama T et al. Immunohistochemical analysis of cancer stem cell markers in pancreatic adenocarcinoma patients after neoadjuvant chemoradiotherapy. BMC Cancer 2014;14:687.
  • 7. Rich JN. Cancer stem cells: understanding tumor hierarchy and heterogeneity. Medicine (Baltimore). 2016;95(Suppl 1):S2-S7.
  • 8. Zhao W, Li Y, Zhang X. Stemness-Related Markers in Cancer. Cancer Transl Med. 2017;3(3):87-95.
  • 9. Wang Y, Hayward S, Cao M, Thayer K, Cunha G. Cell differentiation lineage in the prostate. Differentiation 2001;68(4):270-9.
  • 10. Trompetter M, Smedts F, van der Wijk J, Schoots C, de Jong HJ, Hopman A et al. Keratin profiling in the developing human prostate. A different approach to understanding epithelial lineage. Anticancer Res 2008;28(1A):237-43.
  • 11. Kwon O, Xin L. Prostate epithelial stem and progenitor cells. Am J Clin Exp Urol. 2014;2(3):209-18.
  • 12. Draffin JE, McFarlane S, Hill A, Johnston PG, Waugh DJ. CD44 potentiates the adherence of metastatic prostate and breast cancer cells to bone marrow endothelial cells. Cancer Res 2004;64(16):5702-11.
  • 13. Lokeshwar BL, Lokeshwar VB, Block NL. Expression of CD44 in prostate cancer cells: association with cell proliferation and invasive potential. Anticancer Res 1995;15(4):1191-8.
  • 14. Shang Z, Cai Q, Zhang M, Zhu S, Ma Y, Sun L et al. Switch from CD44+ cell to EMT cell drives the metastasis of prostate cancer. Oncotarget 2015;6(2):1202-16.
  • 15. Verkaik NS, van Steenbrugge GJ, van Weerden WM, Bussemakers MJ, van der Kwast TH. Silencing of CD44 expression in prostate cancer by hypermethylation of the CD44 promoter region. Lab Invest 2000;80(8):1291-8.

Prostat Adenokarsinomunda CD44 Ekspresyonu: Gleason Derecesi ile Korelasyon

Year 2020, Volume: 22 Issue: 2, 233 - 239, 31.08.2020

Mahi Balcı Gülhan Özdemir

Abstract

Amaç: Bir yüzey adezyon proteini olan CD44, kök hücre belirteci olup prostat glandlarının bazal hücrelerinin yapısal bütünlüğünü korumada görev alır. Prostat karsinogenezisinde de önemli bir rolü olduğu düşünülse de şu ana dek yapılan çalışmalarda elde edilen sonuçlar belirsizdir. Bu çalışma, farklı Gleason büyüme patternlerine sahip tümörlerde ve hiperplastik glandlarda CD44 ekspresyonunu değerlendirmek amacı ile yapılmıştır. 
Gereç ve Yöntemler: Kırıkkale Üniversitesi, Tıp Fakültesi patoloji arşivine ait, 2011 ile 2018 yılları arasında tanı almış, farklı Gleason derecelerine sahip prostat karsinomlu ve benign prostat hiperplazili 80 olgu, çalışmaya dahil edilmiştir. CD44 ile olan immünreaksiyon, pozitif boyanan hücrelerin yüzdesi ile boyanma yoğunluğunun çarpımı olarak değerlendirilmiştir. Ortalama değerler ve anlamlılık Kruskal-Wallis testi kullanılarak belirlenmiş; p<0.05 anlamlı kabul edilmiştir. 
Bulgular: Benign hiperplazi olgularında CD44 boyanması, karsinom olgularına göre daha diffüz ve yoğun idi (p değerleri <0.01-0.005). Ekspresyon seviyesi, histolojik derece arttıkça kademeli olarak düşüş gösterdi. Pattern 3 tümörler, pattern 4 tümörlerden daha yüksek oranda pozitif hücre sayısına sahipti (p<0.01). Pattern 5 tümörlerde CD44 ile boyanma olmadı. Pattern 4 tümörlerde ise az sayıda hücrede pozitiflik görüldü. Pattern 4 ve 5 arasında, CD44 boyanması bakımından anlamlı farklılık gözlenmedi ((p=0.278).
Sonuç: Bu çalışmada, bir kez kanseröz özellikler kazanıldıktan sonra hücrelerin CD44 ekspresyonu kabiliyetini yitirme eğiliminde olduğu sonucuna vardık. Düşük dereceli kanserlerdeki CD44 ekspresyonunun, tümör dokusunu diferansiye ve gland oluşturabilen durumda kalmasını sağladığını, bu nedenle CD44’ün prostat karsinogenezisinde bir tümör kök hücre marker’ı gibi davranmayabileceğini düşündük.

Keywords

Prostat karsinogenezis Kök Hücreler Prostatik Hiperplazi Keratinler

References

  • 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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.
  • 2. Crona DJ, Whang Y. Androgen receptor-dependent and -independent mechanisms involved in prostate cancer therapy resistance. Cancers (Basel). 2017;9(6):67.
  • 3. Chen C, Zhao S, Karnad A, Freeman JW. The biology and role of CD44 in cancer progression: therapeutic implications. J Hematol Oncol. 2018;11(1):64.
  • 4. Harris KS, Kerr BA. Prostate cancer stem cell markers drive progression, therapeutic resistance, and bone metastasis. Stem Cells Int. 2017;(2):1-9.
  • 5. Kalantari E, Asgari M, Nikpanah S, Salarieh N, Asadi Lari MH, Madjd Z. Co-Expression of putative cancer stem cell markers CD44 and CD133 in prostate carcinomas. Pathol Oncol Res. 2017;23(4):793-802.
  • 6. Mizukami T, Kamachi H, Mitsuhashi T, Tsuruga Y, Hatanaka Y, Kamiyama T et al. Immunohistochemical analysis of cancer stem cell markers in pancreatic adenocarcinoma patients after neoadjuvant chemoradiotherapy. BMC Cancer 2014;14:687.
  • 7. Rich JN. Cancer stem cells: understanding tumor hierarchy and heterogeneity. Medicine (Baltimore). 2016;95(Suppl 1):S2-S7.
  • 8. Zhao W, Li Y, Zhang X. Stemness-Related Markers in Cancer. Cancer Transl Med. 2017;3(3):87-95.
  • 9. Wang Y, Hayward S, Cao M, Thayer K, Cunha G. Cell differentiation lineage in the prostate. Differentiation 2001;68(4):270-9.
  • 10. Trompetter M, Smedts F, van der Wijk J, Schoots C, de Jong HJ, Hopman A et al. Keratin profiling in the developing human prostate. A different approach to understanding epithelial lineage. Anticancer Res 2008;28(1A):237-43.
  • 11. Kwon O, Xin L. Prostate epithelial stem and progenitor cells. Am J Clin Exp Urol. 2014;2(3):209-18.
  • 12. Draffin JE, McFarlane S, Hill A, Johnston PG, Waugh DJ. CD44 potentiates the adherence of metastatic prostate and breast cancer cells to bone marrow endothelial cells. Cancer Res 2004;64(16):5702-11.
  • 13. Lokeshwar BL, Lokeshwar VB, Block NL. Expression of CD44 in prostate cancer cells: association with cell proliferation and invasive potential. Anticancer Res 1995;15(4):1191-8.
  • 14. Shang Z, Cai Q, Zhang M, Zhu S, Ma Y, Sun L et al. Switch from CD44+ cell to EMT cell drives the metastasis of prostate cancer. Oncotarget 2015;6(2):1202-16.
  • 15. Verkaik NS, van Steenbrugge GJ, van Weerden WM, Bussemakers MJ, van der Kwast TH. Silencing of CD44 expression in prostate cancer by hypermethylation of the CD44 promoter region. Lab Invest 2000;80(8):1291-8.
There are 15 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Mahi Balcı 0000-0001-5836-2344

Gülhan Özdemir This is me 0000-0001-6564-0736

Publication Date August 31, 2020
Submission Date March 18, 2020
Published in Issue Year 2020 Volume: 22 Issue: 2

Cite

APA Balcı, M., & Özdemir, G. (2020). CD44 EXPRESSION IN PROSTATIC ADENOCARCINOMA: CORRELATION WITH GLEASON GRADES. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi, 22(2), 233-239.
AMA Balcı M, Özdemir G. CD44 EXPRESSION IN PROSTATIC ADENOCARCINOMA: CORRELATION WITH GLEASON GRADES. Kırıkkale Uni Med J. August 2020;22(2):233-239.
Chicago Balcı, Mahi, and Gülhan Özdemir. “CD44 EXPRESSION IN PROSTATIC ADENOCARCINOMA: CORRELATION WITH GLEASON GRADES”. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 22, no. 2 (August 2020): 233-39.
EndNote Balcı M, Özdemir G (August 1, 2020) CD44 EXPRESSION IN PROSTATIC ADENOCARCINOMA: CORRELATION WITH GLEASON GRADES. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 22 2 233–239.
IEEE M. Balcı and G. Özdemir, “CD44 EXPRESSION IN PROSTATIC ADENOCARCINOMA: CORRELATION WITH GLEASON GRADES”, Kırıkkale Uni Med J, vol. 22, no. 2, pp. 233–239, 2020.
ISNAD Balcı, Mahi - Özdemir, Gülhan. “CD44 EXPRESSION IN PROSTATIC ADENOCARCINOMA: CORRELATION WITH GLEASON GRADES”. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 22/2 (August 2020), 233-239.
JAMA Balcı M, Özdemir G. CD44 EXPRESSION IN PROSTATIC ADENOCARCINOMA: CORRELATION WITH GLEASON GRADES. Kırıkkale Uni Med J. 2020;22:233–239.
MLA Balcı, Mahi and Gülhan Özdemir. “CD44 EXPRESSION IN PROSTATIC ADENOCARCINOMA: CORRELATION WITH GLEASON GRADES”. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi, vol. 22, no. 2, 2020, pp. 233-9.
Vancouver Balcı M, Özdemir G. CD44 EXPRESSION IN PROSTATIC ADENOCARCINOMA: CORRELATION WITH GLEASON GRADES. Kırıkkale Uni Med J. 2020;22(2):233-9.
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