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Meme karsinomlarında VEGF ve p53 ekspresyonunun diğer prognostik parametrelerle ilişkisi

Year 2022, Volume: 15 Issue: 4, 702 - 710, 01.10.2022
https://doi.org/10.31362/patd.1088441

Abstract

Amaç: Meme karsinomlarında VEGF ve p53 immünhistokimyasal ekspresyonları ile diğer klinikopatolojik prognostik parametreler arasındaki ilişkiyi değerlendirmeyi amaçladık.
Gereç ve yöntem: Toplam 74 primer meme kanseri tanılı parafin gömülü bloktan hazırlanan kesitler incelendi ve VEGF, p53, östrojen, progesteron, Cerb-B2 ve Ki-67 immünhistokimyasal boyaları uygulandı. VEGF ve p53'ün diğer immünhistokimyasal boyalar ve prognostik parametrelerle ilişkisi araştırıldı.
Bulgular: VEGF ile lateralizasyon, derece ve lenfovasküler invazyon arasında istatistiksel olarak anlamlı sonuçlar elde edildi. Ayrıca tüm normal meme dokularında VEGF ile boyanma görülmezken, tümör in situdan invaziv hale progrese oldukça VEGF boyanma yoğunluğunda artış izlendi. İnvaziv tümör düşük dereceden orta dereceye progrese olurken VEGF boyanması artarken, orta dereceden yüksek dereceye doğru boyanmada düşüş izlendi.
P53 ile Ki-67, derece ve çap arasında istatistiksel olarak anlamlı, östrojen ile ise ters korelasyon bulundu. Tümörün in situ ve invaziv alanlarında p53 ekspresyonunda artış izlendi.
Sonuç: Tümörün in situ ve invaziv alanlarında benzer p53 ekspresyon oranlarının izlenmiş olması, in situ evredeki tümörün davranışının tahmin edilmesi ve tedavinin yönlendirilmesinde yardımcı olabilir. Verilerimize göre VEGF'ün tümör progresyonundaki rolü ve birçok prognostik faktörle ilişkisi belirgindir.

References

  • Referans1. Global Cancer Observatory, France: International Agency for Research on Cancer, World Health Organization. Breast Cancer Incidence, Mortality and Prevalence Worldwide in 2020; [accessed February 26, 2022]. Available from https://gco.iarc.fr/today/home
  • Referans2. Norberg T, Jansson T, Sjoügren S, et al. Overview on human breast cancer with focus on prognostic and predictive factors with special attention on the tumour suppressor gene p53. Acta Oncologica 1996;35:96-102.
  • Referans3. Korkolis DP, Tsoli E, Fouskakis D, et al. Tumor histology and stage but not p53, Her2-neu or cathepsin-D expression are independent prognostic factors in breast cancer patients. Anticancer Res. 2004;24:2061-2068.
  • Referans4. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86(3):353–364.
  • Referans5. Maschio LB, Madallozo BB, Capellasso BA, et al. Immunohistochemical investigation of the angiogenic proteins VEGF, HIF-1α and CD34 in invasive ductal carcinoma of the breast. Acta Histochem. 2014;116(1):148-157.
  • Referans6. Ludovini V, Sidoni A, Pistola L, et al. Evaluation of the prognostic role of vascular endothelial growth factor and microvessel density in stages I and II breast cancer patients. Breast Cancer Res Treat. 2003;81:159–168.
  • Referans7. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long term follow up. Histopathology 1991;19:403-410.
  • Referans8. Dhakal HP, Naume B, Synnestvedt M, et al. Expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and 2 in invasive breast carcinoma: prognostic significance and relationship with markers for aggressiveness. Histopathology 2012;61:350–364.
  • Referans9. Liu C, Zhang H, Shuang C, et al. Alternation of ER, PR, HER-2/neu, and P53 protein expression in ductal breast carcinomas and clinical implications. Med Oncol. 2010;27(3):747-752.
  • Referans10. Ogava Y, Moriya T, Kato Y, et al. Immunohistochemical Assessment for Estrogen Receptor and Progesterone Receptor Status in Breast Cancer: Analysis for a Cut-off Point as the Predictor for Endocrine Therapy. Breast Cancer. 2004;11:267-275.
  • Referans11. Wolff AC, Hammond MEH, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31:3997-4013.
  • Referans12. Goldhirsch A, Ingle JN, Gelber RD, et al. Thresholds for therapies: highlights of the St Galen International Expert Consensus on The Primary Therapy of Early Breast Cancer 2009. Ann Oncol. 2009;20(8):1319-1329.
  • Referans13. Kanyılmaz G, Yavuz BB, Aktan M, Karaağaç M, Uyar M, Fındık S. Prognostic Importance of Ki-67 in Breast Cancer and Its Relationship with Other Prognostic Factors. Eur J Breast Health 2019;15(4):256-261.
  • Referans14. Done SJ, Eskardarian S, Bull S, Redston M, Andrulis IL. p53 missense mutations in microdissected high-grade ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2001;93(9):700-704.
  • Referans15. Sirvent JJ, Salvadó MT, Santafé M, et al. p53 in breast cancer. Its relation to histological grade, lymph-node status, hormone receptors, cell-proliferation fraction (ki-67) and c-erbB-2. Immunohistogemical study of 153 cases. Histol Histopathol. 1995;10(3):531-539.
  • Referans16. Sun L, Yu D-h, Sun S-Y, Zhuo S-C, Cao S-s, Wei L. Expression of ER, PR, HER-2, COX-2 and VEGF in primary and relapsed/metastatic breast cancers. Cell Biochemistry and Biophysics. 2013;68(3):511-516.
  • Referans17. Takahashi H, Shibuya M. The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond). 2005;109(3):227–241.
  • Referans18. Boocock CA, Charnock-Jones DS, Sharkey AM, et al. Expression of Vascular Endothelial Growth Factor and Its Receptors flt and KDR in ovarian carcinoma. J Natl Cancer Inst. 1995;87(7):506–516.
  • Referans19. Fontanini G, Boldrini L, Chinè S, et al. Expression of vascular endothelial growth factor mRNA in non-small-cell lung carcinomas. Br J Cancer 1999;79(2):363–369.
  • Referans20. Brown LF, Berse B, Jackman RW, et al. Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol. 1993;143(5):1255–1262.
  • Referans21. Carpenter PM, Chen W-P, Mendez A, McLaren CE, Su M-Y. Angiogenesis in the progression of breast ductal proliferations. Int J Surg Pathol. 2011;19(3):335–341.
  • Referans22. Guidi AJ, Schnitt SJ, Fischer L, et al. Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in patients with ductal carcinoma in situ of the breast. Cancer 1997;80(10):1945–1953.
  • Referans23. Wang Z, Shi Q, Wang Z, et al. Clinicopathologic correlation of cancer stem cell markers CD44, CD24, VEGF and HIF-1α in ductal carcinoma in situ and invasive ductal carcinoma of breast: An immunohistochemistry-based pilot study. Pathol Res Pract. 2011;207:505-513.
  • Referans24. Ghasemi M, Emadian O, Naghshvar F, et al. Immunohistochemical expression of Vascular Endothelial Growth Factor and its correlation with tumor grade in breast ductal carcinoma. Acta Medica Iran. 2011;49(12):776-779.

Relationship of VEGF and p53 expression with other prognostic parameters in breast carcinomas

Year 2022, Volume: 15 Issue: 4, 702 - 710, 01.10.2022
https://doi.org/10.31362/patd.1088441

Abstract

Purpose: We aimed to evaluate the relationship between VEGF and p53 immunohistochemical expressions and other clinicopathological prognostic parameters in breast carcinomas.
Materials and methods: Sections prepared from paraffin-embedded blocks diagnosed with a total of 74 primary breast cancers were examined and VEGF, p53, estrogen, progesterone, Cerb-B2 and Ki-67 immunohistochemical stains were applied. The relationship of VEGF and p53 with other immunohistochemical stains and prognostic parameters was investigated.
Results: Statistically significant results were obtained across VEGF with lateralization, grade and lymphovascular invasion. Furthermore, while no staining with VEGF was observed in any of the normal breast tissues, an increase in VEGF expression was observed as the tumor progressed from carcinoma in situ to invasive carcinoma. It was observed that VEGF expression increased while the invasive tumor progressed from low grade to moderate grade, whereas VEGF expression decreased when it progressed from moderate to high grade.
Statistically significant correlation among p53 with Ki-67, grade, diameter and opposite correlation between p53 and estrogen was found. There was increased p53 expressionin the in situ and invasive field of tumor.
Conclusion: Similar p53 expression rates in in situ and invasive areas of the tumor may be helpful in predicting the behavior of the tumor in the in situ stage and in guiding the treatment. According to our data, the role of VEGF in tumor progression and its relationship with many prognostic factors is evident.

References

  • Referans1. Global Cancer Observatory, France: International Agency for Research on Cancer, World Health Organization. Breast Cancer Incidence, Mortality and Prevalence Worldwide in 2020; [accessed February 26, 2022]. Available from https://gco.iarc.fr/today/home
  • Referans2. Norberg T, Jansson T, Sjoügren S, et al. Overview on human breast cancer with focus on prognostic and predictive factors with special attention on the tumour suppressor gene p53. Acta Oncologica 1996;35:96-102.
  • Referans3. Korkolis DP, Tsoli E, Fouskakis D, et al. Tumor histology and stage but not p53, Her2-neu or cathepsin-D expression are independent prognostic factors in breast cancer patients. Anticancer Res. 2004;24:2061-2068.
  • Referans4. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86(3):353–364.
  • Referans5. Maschio LB, Madallozo BB, Capellasso BA, et al. Immunohistochemical investigation of the angiogenic proteins VEGF, HIF-1α and CD34 in invasive ductal carcinoma of the breast. Acta Histochem. 2014;116(1):148-157.
  • Referans6. Ludovini V, Sidoni A, Pistola L, et al. Evaluation of the prognostic role of vascular endothelial growth factor and microvessel density in stages I and II breast cancer patients. Breast Cancer Res Treat. 2003;81:159–168.
  • Referans7. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long term follow up. Histopathology 1991;19:403-410.
  • Referans8. Dhakal HP, Naume B, Synnestvedt M, et al. Expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and 2 in invasive breast carcinoma: prognostic significance and relationship with markers for aggressiveness. Histopathology 2012;61:350–364.
  • Referans9. Liu C, Zhang H, Shuang C, et al. Alternation of ER, PR, HER-2/neu, and P53 protein expression in ductal breast carcinomas and clinical implications. Med Oncol. 2010;27(3):747-752.
  • Referans10. Ogava Y, Moriya T, Kato Y, et al. Immunohistochemical Assessment for Estrogen Receptor and Progesterone Receptor Status in Breast Cancer: Analysis for a Cut-off Point as the Predictor for Endocrine Therapy. Breast Cancer. 2004;11:267-275.
  • Referans11. Wolff AC, Hammond MEH, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31:3997-4013.
  • Referans12. Goldhirsch A, Ingle JN, Gelber RD, et al. Thresholds for therapies: highlights of the St Galen International Expert Consensus on The Primary Therapy of Early Breast Cancer 2009. Ann Oncol. 2009;20(8):1319-1329.
  • Referans13. Kanyılmaz G, Yavuz BB, Aktan M, Karaağaç M, Uyar M, Fındık S. Prognostic Importance of Ki-67 in Breast Cancer and Its Relationship with Other Prognostic Factors. Eur J Breast Health 2019;15(4):256-261.
  • Referans14. Done SJ, Eskardarian S, Bull S, Redston M, Andrulis IL. p53 missense mutations in microdissected high-grade ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2001;93(9):700-704.
  • Referans15. Sirvent JJ, Salvadó MT, Santafé M, et al. p53 in breast cancer. Its relation to histological grade, lymph-node status, hormone receptors, cell-proliferation fraction (ki-67) and c-erbB-2. Immunohistogemical study of 153 cases. Histol Histopathol. 1995;10(3):531-539.
  • Referans16. Sun L, Yu D-h, Sun S-Y, Zhuo S-C, Cao S-s, Wei L. Expression of ER, PR, HER-2, COX-2 and VEGF in primary and relapsed/metastatic breast cancers. Cell Biochemistry and Biophysics. 2013;68(3):511-516.
  • Referans17. Takahashi H, Shibuya M. The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions. Clin Sci (Lond). 2005;109(3):227–241.
  • Referans18. Boocock CA, Charnock-Jones DS, Sharkey AM, et al. Expression of Vascular Endothelial Growth Factor and Its Receptors flt and KDR in ovarian carcinoma. J Natl Cancer Inst. 1995;87(7):506–516.
  • Referans19. Fontanini G, Boldrini L, Chinè S, et al. Expression of vascular endothelial growth factor mRNA in non-small-cell lung carcinomas. Br J Cancer 1999;79(2):363–369.
  • Referans20. Brown LF, Berse B, Jackman RW, et al. Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol. 1993;143(5):1255–1262.
  • Referans21. Carpenter PM, Chen W-P, Mendez A, McLaren CE, Su M-Y. Angiogenesis in the progression of breast ductal proliferations. Int J Surg Pathol. 2011;19(3):335–341.
  • Referans22. Guidi AJ, Schnitt SJ, Fischer L, et al. Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in patients with ductal carcinoma in situ of the breast. Cancer 1997;80(10):1945–1953.
  • Referans23. Wang Z, Shi Q, Wang Z, et al. Clinicopathologic correlation of cancer stem cell markers CD44, CD24, VEGF and HIF-1α in ductal carcinoma in situ and invasive ductal carcinoma of breast: An immunohistochemistry-based pilot study. Pathol Res Pract. 2011;207:505-513.
  • Referans24. Ghasemi M, Emadian O, Naghshvar F, et al. Immunohistochemical expression of Vascular Endothelial Growth Factor and its correlation with tumor grade in breast ductal carcinoma. Acta Medica Iran. 2011;49(12):776-779.
There are 24 citations in total.

Details

Primary Language Turkish
Subjects Pathology
Journal Section Research Article
Authors

Perihan Özlem Doğan Ulutaş 0000-0003-4945-6183

Sevgi Bakarış 0000-0002-3165-0650

Gülçin Güler Şimşek 0000-0001-7710-4631

Publication Date October 1, 2022
Submission Date March 15, 2022
Acceptance Date May 30, 2022
Published in Issue Year 2022 Volume: 15 Issue: 4

Cite

AMA Doğan Ulutaş PÖ, Bakarış S, Güler Şimşek G. Meme karsinomlarında VEGF ve p53 ekspresyonunun diğer prognostik parametrelerle ilişkisi. Pam Med J. October 2022;15(4):702-710. doi:10.31362/patd.1088441

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