Research Article
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Concurrent expression of immunhistochemical parameters in breast cancer patients; clinical implications and consistency with Bloom-Richardson grading system

Year 2023, Volume: 40 Issue: 2, 294 - 299, 19.07.2023

Abstract

We sought to determine prognostic importance of expression p53, c-erbB-2 (also known HER2/neu or HER2), estrogen receptor and progesterone receptor in breast cancer patients by investigating their relationship with histopathological and clinical parameters. We also investigated whether different parameters other than Bloom-Richardson grading system might be used in classification of breast cancer patients on the basis of concurrent expression of immunhistochemical parameters. Seventy-one invasive ductal carcinoma patients were included. We studied immunhistochemical parameters including, estrogen receptor, progesteron receptor, p53 and c-erbB-2. Specimens that were archived in pathology department were re-assessed to determine necrosis, lymph and blood vessel invasion, perineural invasion, peritumoral inflamatory reaction characteristics. Bloom-Richardson grading system was applied for each specimen. Multivariate discriminant analysis was performed to test the relationship between Bloom-Richardson system and immunhistochemical parameters. Mean age was 50.79 ± 11.92. Forty-eight patients (67.6%) were estrogen receptor positive, 34 (47.9%) were progesterone receptor positive, 38 (53.5%) were p53 positive and 46 (64.8%) were c-erbB-2 positive. Necrosis was less common and peritumoral inflammatory reaction was more common among estrogen receptor positive patients. According to the discriminant analysis, 52.1% of patients with concurrent expression of ER, PR, p53 and c-erbB-2 were correctly classified according to overall Bloom-Richardson grade, 49.3% were correctly classified according to nuclear pleomorphism score and 77.5% were correctly classified according to mitotic count. Prognostic classification of patients could be done on the basis of mitotic characteristics of the tumor. Further study is warranted to establish the standard threshold for mitotic count for breast tumors of different types.

Thanks

Thanks to the biostatistics and radiation oncology departments of Ondokz Mayıs Univercity

References

  • 1. Breast. In: Rosai J. Ackerman’s Surgical Pathology (10th ed). Vol 2. China, Elsevier Mosby, 2011; 1659-1770.
  • 2. Howard EM, Lau SK, Lyles RH, Birdsong GG, Tadros TS, Umbreit JN, et al. Correlation and expression of p53, HER-2, vascular endothelial growth factor (VEGF), and E-cadherin in a high-risk breast-cancer population. Int J Clin Oncol 2004; 9: 154-160.
  • 3. General considerations. In: Tavassoli FA. Pathology of the Breast (2nd ed). Stamford: Appleton and Lange; 1999; 27-74.
  • 4. Barbareschi M, Leonardi E, Mauri FA, Serio G, Dalla PP. p53 and c-erbB2 protein expression in breast carcinoma. An immunohistochemical study including correlations with receptor status, proliferation markers, and clinical stage in human breast cancer. Am J Clin Pathol 1992; 98: 408-418.
  • 5. Dimitrakakis C, Konstadoulakis M, Messaris E, Kymionis G, Karayannis M, Panoussopoulos D, et al. Molecular markers in breast cancer: Can we use c-erbB-2, p53, bcl-2, and bax gene expression as prognostic factors ? The Breast 2002; 11: 279-285.
  • 6. Eissa S, Khalifa A, El-Gharib A, Salah N, Mohamed MK. Multivariate analysis of DNA ploidy, p53, c-erbB-2 proteins, EGFR, and steroid hormone receptors for prediction of poor short term prognosis in breast cancer. Anticancer Research 1997; 17: 1417-1424.
  • 7. El-Ahmady O, El-Salahy E, Mahmoud M, Wahab MA, Eissa S, Khalifa A. Multivariate analysis of Bcl-2, apoptosis, p53 and HER-2/ neu in breast cancer: a short-term follow-up. Anticancer Research 2002; 22: 2493-2500.
  • 8. Kute TE, Russell GB, Zbieranski N, Long R, Johnston S, Williams H, et al. Prognostic markers in node-negative breast cancer: a prospective study. Cytometry Part B (Clinical Cytometry) 2004; 59B: 24-31.
  • 9. Chia SK, Speers CH, Bryce CJ, Hayes MM, Olivotto IA. Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast Cancers without adjuvant systemic therapies. J Clin Oncol 2004; 22: 1630-1637.
  • 10. Dowsett M, Houghton J, Iden C, Salter J, Farndon J, Hern RA, et al. Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, proesterone receptor, EGF receptor and HER2 status. Annals of Oncology 2006; 17:818-826
  • 11. Infiltrating carcinoma: common and familiar special types. In: Tavassoli FA. Pathology of the Breast (2nd ed). Stamford: Appleton and Lange; 1999; 401-480.
  • 12. Grenle RT, Murray T, Bolden S, Wingo PA. Cancer statistics. CA Cancer J Clin 2000; 50: 7-33.
  • 13. Gretarsdottir S, Tryggvadottir L, Jonasson JG, Sigurdsson H, Olafsdottir K, Agnarrsson BA, et al. TP53 mutation analyses on breast carcinomas: a study of parafin embedded archival material. British Journal of Cancer 1996; 74: 555-561.
  • 14. Reed W, Hannisdal E, Boehler PJ, Gundersen S, Host H, Nesland JM. The prognostic value of p53 and c-erbB-2 immunostaining is overrated for patients with lymph node negatıve breast carcinoma. A multıvariate analysis of prognostic factors in 613 patients with follow-up of 14-30 years. Cancer 2000; 88: 804-813.
  • 15. Rodrigues NA, Dillon D, Carter D, Parisot N, Haffty BG. Differences in the pathologic and molecular features of intraductal breast carcinoma between younger and older women. Cancer 2003; 97: 1393-1403.
  • 16. Samur M, Karaveli Ş, Bozcuk H, Peştereli E, Ozdogan M, Yıldız M, et al. A novel method of reporting c-erbB-2 overexpression: Correlation with grade but not other prognostic parameters in breast cancer. Turk J Med Sci 2003; 33: 363-368.
  • 17. Soslow RA, Carlson DL, Horenstein MG, Osborne MP. A comparison of cell cycle markers in well differantiated lobular and ductal carcinomas. Breast Cancer Research and Treatment 2000; 61: 161-170.
  • 18. Matsuo K, Fukutomi T, Tsuda H, Akashi-Tanaka S, Shimizu C, Hasegawa T. Differences in estrogen receptor status, HER2, and p53 comparing metachronous bilateral breast carcinoma. J Surg Oncol 2001; 77: 31-34.
  • 19. Levesque MA, Diamandis EP, Yu H, Sutherland DJ. Quantitative analysis of mutant p53 protein in breast tumor cytosol and study of association with other biochemical prognostic indicators in breast cancer. Breast Cancer Res Treat 1994; 30: 179-195.
  • 20. Zavagno G, Meggiolaro A, Pluchinotta A, Bozza F, Favretti F, Marconato R, et al. Influence of age and menopausal status on pathologic and biologic features of breast cancer. The Breast 2000; 9: 320-328
  • 21. Ko SS, Na YS, Yoon CS, Park JY, Kim HS, Hur MH, et al. The Significance of c-erbB-2 overexpression and p53 expression in patients with axillary lymph node negative breast cancer: a tissue microarray study. Int J Surg Pathol 2007; 15: 98-109.
  • 22. Cattoretti G, Andreola S, Clemente C, D’Amato L, Rilke F. Vimentin and p53 expression on epidermal growth factor receptor positive, estrogen receptor negative breast carcinomas. Br J Cancer 1988; 57: 353-357.
  • 23. Ilhan E, Ureyen O, Alpdogan O, Senlikci A, Alay D, Gokcelli U, et al. Is molecular subtypes of breast cancer related with axillary involvement ? A retrospective study of 86 cases. Acta Medica Mediterranea 2017; 33: 393-397.
  • 24. Jafarimojarrad E, Javidroozi M, Ghavamzadeh A. Breast cancer in Iran: an immunohistochemical approach. ASCO Annual Meeting 2002; (Abstract) 2988.
  • 25. Hoda SA. Invasive ductal carcinoma: Assessment of prognosis with morphologic and biologic markers. In: Hosa SA, Brogi E, Koerner FC, Rosen PP. Rosen’s Breast Pathology (4th ed). Philedelphia, USA: Lippincott Williams&Wilkins; 2014; 413-467.
  • 26. Fisher ER, Sass R, Fisher B. Pathologic findings from the national surgical adjuvant breast project. Correlations with concordant and discordant estrogen and progesterone receptors. Cancer 1987; 59: 1554-1559.
  • 27. del Sordo R, Bellezza G, Ferri I, Pireddu A, Colella R, Sidoni A. Mitotic index matter: how to improve the assessment of mitosis in order to beter classify G2 breast cancer and luminal A category. Histology and Histopathology 2018; 33: 81-88
  • 28. Veta M, van Diest PJ, Jiva M, Al-Janabi S, Pluim JP.W. Mitosis counting in breast cancer: object-level interobserver agreement and comparison to an automatic method. Plos one 2016; 11 (8) https://doi.org/ 10.1371 /journal.pone.0161286
  • 29. Chang JM, McCullough AE, Dueck AC, Kosiorek HE, Ocal IT, Lidner TK, et al. Backto basics: Traditional Nottingham grade mitotic counts alone are significant in predicting survival in invasive breast carcinoma. Ann Surg Oncol 2015; 22: 509-515
  • 30. Buhmeida A, Al-Maghrabi J, Merdad A, Al-Thubaity F, Chaudhary A, Garı M, et al. Prognostic value of mitotic counts in breast cancer of Saudi arabian patients. Anticancer Research 2011; 31: 97-103
Year 2023, Volume: 40 Issue: 2, 294 - 299, 19.07.2023

Abstract

References

  • 1. Breast. In: Rosai J. Ackerman’s Surgical Pathology (10th ed). Vol 2. China, Elsevier Mosby, 2011; 1659-1770.
  • 2. Howard EM, Lau SK, Lyles RH, Birdsong GG, Tadros TS, Umbreit JN, et al. Correlation and expression of p53, HER-2, vascular endothelial growth factor (VEGF), and E-cadherin in a high-risk breast-cancer population. Int J Clin Oncol 2004; 9: 154-160.
  • 3. General considerations. In: Tavassoli FA. Pathology of the Breast (2nd ed). Stamford: Appleton and Lange; 1999; 27-74.
  • 4. Barbareschi M, Leonardi E, Mauri FA, Serio G, Dalla PP. p53 and c-erbB2 protein expression in breast carcinoma. An immunohistochemical study including correlations with receptor status, proliferation markers, and clinical stage in human breast cancer. Am J Clin Pathol 1992; 98: 408-418.
  • 5. Dimitrakakis C, Konstadoulakis M, Messaris E, Kymionis G, Karayannis M, Panoussopoulos D, et al. Molecular markers in breast cancer: Can we use c-erbB-2, p53, bcl-2, and bax gene expression as prognostic factors ? The Breast 2002; 11: 279-285.
  • 6. Eissa S, Khalifa A, El-Gharib A, Salah N, Mohamed MK. Multivariate analysis of DNA ploidy, p53, c-erbB-2 proteins, EGFR, and steroid hormone receptors for prediction of poor short term prognosis in breast cancer. Anticancer Research 1997; 17: 1417-1424.
  • 7. El-Ahmady O, El-Salahy E, Mahmoud M, Wahab MA, Eissa S, Khalifa A. Multivariate analysis of Bcl-2, apoptosis, p53 and HER-2/ neu in breast cancer: a short-term follow-up. Anticancer Research 2002; 22: 2493-2500.
  • 8. Kute TE, Russell GB, Zbieranski N, Long R, Johnston S, Williams H, et al. Prognostic markers in node-negative breast cancer: a prospective study. Cytometry Part B (Clinical Cytometry) 2004; 59B: 24-31.
  • 9. Chia SK, Speers CH, Bryce CJ, Hayes MM, Olivotto IA. Ten-year outcomes in a population-based cohort of node-negative, lymphatic, and vascular invasion-negative early breast Cancers without adjuvant systemic therapies. J Clin Oncol 2004; 22: 1630-1637.
  • 10. Dowsett M, Houghton J, Iden C, Salter J, Farndon J, Hern RA, et al. Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, proesterone receptor, EGF receptor and HER2 status. Annals of Oncology 2006; 17:818-826
  • 11. Infiltrating carcinoma: common and familiar special types. In: Tavassoli FA. Pathology of the Breast (2nd ed). Stamford: Appleton and Lange; 1999; 401-480.
  • 12. Grenle RT, Murray T, Bolden S, Wingo PA. Cancer statistics. CA Cancer J Clin 2000; 50: 7-33.
  • 13. Gretarsdottir S, Tryggvadottir L, Jonasson JG, Sigurdsson H, Olafsdottir K, Agnarrsson BA, et al. TP53 mutation analyses on breast carcinomas: a study of parafin embedded archival material. British Journal of Cancer 1996; 74: 555-561.
  • 14. Reed W, Hannisdal E, Boehler PJ, Gundersen S, Host H, Nesland JM. The prognostic value of p53 and c-erbB-2 immunostaining is overrated for patients with lymph node negatıve breast carcinoma. A multıvariate analysis of prognostic factors in 613 patients with follow-up of 14-30 years. Cancer 2000; 88: 804-813.
  • 15. Rodrigues NA, Dillon D, Carter D, Parisot N, Haffty BG. Differences in the pathologic and molecular features of intraductal breast carcinoma between younger and older women. Cancer 2003; 97: 1393-1403.
  • 16. Samur M, Karaveli Ş, Bozcuk H, Peştereli E, Ozdogan M, Yıldız M, et al. A novel method of reporting c-erbB-2 overexpression: Correlation with grade but not other prognostic parameters in breast cancer. Turk J Med Sci 2003; 33: 363-368.
  • 17. Soslow RA, Carlson DL, Horenstein MG, Osborne MP. A comparison of cell cycle markers in well differantiated lobular and ductal carcinomas. Breast Cancer Research and Treatment 2000; 61: 161-170.
  • 18. Matsuo K, Fukutomi T, Tsuda H, Akashi-Tanaka S, Shimizu C, Hasegawa T. Differences in estrogen receptor status, HER2, and p53 comparing metachronous bilateral breast carcinoma. J Surg Oncol 2001; 77: 31-34.
  • 19. Levesque MA, Diamandis EP, Yu H, Sutherland DJ. Quantitative analysis of mutant p53 protein in breast tumor cytosol and study of association with other biochemical prognostic indicators in breast cancer. Breast Cancer Res Treat 1994; 30: 179-195.
  • 20. Zavagno G, Meggiolaro A, Pluchinotta A, Bozza F, Favretti F, Marconato R, et al. Influence of age and menopausal status on pathologic and biologic features of breast cancer. The Breast 2000; 9: 320-328
  • 21. Ko SS, Na YS, Yoon CS, Park JY, Kim HS, Hur MH, et al. The Significance of c-erbB-2 overexpression and p53 expression in patients with axillary lymph node negative breast cancer: a tissue microarray study. Int J Surg Pathol 2007; 15: 98-109.
  • 22. Cattoretti G, Andreola S, Clemente C, D’Amato L, Rilke F. Vimentin and p53 expression on epidermal growth factor receptor positive, estrogen receptor negative breast carcinomas. Br J Cancer 1988; 57: 353-357.
  • 23. Ilhan E, Ureyen O, Alpdogan O, Senlikci A, Alay D, Gokcelli U, et al. Is molecular subtypes of breast cancer related with axillary involvement ? A retrospective study of 86 cases. Acta Medica Mediterranea 2017; 33: 393-397.
  • 24. Jafarimojarrad E, Javidroozi M, Ghavamzadeh A. Breast cancer in Iran: an immunohistochemical approach. ASCO Annual Meeting 2002; (Abstract) 2988.
  • 25. Hoda SA. Invasive ductal carcinoma: Assessment of prognosis with morphologic and biologic markers. In: Hosa SA, Brogi E, Koerner FC, Rosen PP. Rosen’s Breast Pathology (4th ed). Philedelphia, USA: Lippincott Williams&Wilkins; 2014; 413-467.
  • 26. Fisher ER, Sass R, Fisher B. Pathologic findings from the national surgical adjuvant breast project. Correlations with concordant and discordant estrogen and progesterone receptors. Cancer 1987; 59: 1554-1559.
  • 27. del Sordo R, Bellezza G, Ferri I, Pireddu A, Colella R, Sidoni A. Mitotic index matter: how to improve the assessment of mitosis in order to beter classify G2 breast cancer and luminal A category. Histology and Histopathology 2018; 33: 81-88
  • 28. Veta M, van Diest PJ, Jiva M, Al-Janabi S, Pluim JP.W. Mitosis counting in breast cancer: object-level interobserver agreement and comparison to an automatic method. Plos one 2016; 11 (8) https://doi.org/ 10.1371 /journal.pone.0161286
  • 29. Chang JM, McCullough AE, Dueck AC, Kosiorek HE, Ocal IT, Lidner TK, et al. Backto basics: Traditional Nottingham grade mitotic counts alone are significant in predicting survival in invasive breast carcinoma. Ann Surg Oncol 2015; 22: 509-515
  • 30. Buhmeida A, Al-Maghrabi J, Merdad A, Al-Thubaity F, Chaudhary A, Garı M, et al. Prognostic value of mitotic counts in breast cancer of Saudi arabian patients. Anticancer Research 2011; 31: 97-103
There are 30 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Article
Authors

Dilek Yılmaz 0000-0003-4193-4558

Filiz  Karagöz 0000-0001-6621-3920

Early Pub Date August 1, 2023
Publication Date July 19, 2023
Submission Date October 19, 2022
Acceptance Date February 14, 2023
Published in Issue Year 2023 Volume: 40 Issue: 2

Cite

APA Yılmaz, D., & Karagöz, F. (2023). Concurrent expression of immunhistochemical parameters in breast cancer patients; clinical implications and consistency with Bloom-Richardson grading system. Journal of Experimental and Clinical Medicine, 40(2), 294-299.
AMA Yılmaz D, Karagöz F. Concurrent expression of immunhistochemical parameters in breast cancer patients; clinical implications and consistency with Bloom-Richardson grading system. J. Exp. Clin. Med. July 2023;40(2):294-299.
Chicago Yılmaz, Dilek, and Filiz Karagöz. “Concurrent Expression of Immunhistochemical Parameters in Breast Cancer Patients; Clinical Implications and Consistency With Bloom-Richardson Grading System”. Journal of Experimental and Clinical Medicine 40, no. 2 (July 2023): 294-99.
EndNote Yılmaz D, Karagöz F (July 1, 2023) Concurrent expression of immunhistochemical parameters in breast cancer patients; clinical implications and consistency with Bloom-Richardson grading system. Journal of Experimental and Clinical Medicine 40 2 294–299.
IEEE D. Yılmaz and F. Karagöz, “Concurrent expression of immunhistochemical parameters in breast cancer patients; clinical implications and consistency with Bloom-Richardson grading system”, J. Exp. Clin. Med., vol. 40, no. 2, pp. 294–299, 2023.
ISNAD Yılmaz, Dilek - Karagöz, Filiz . “Concurrent Expression of Immunhistochemical Parameters in Breast Cancer Patients; Clinical Implications and Consistency With Bloom-Richardson Grading System”. Journal of Experimental and Clinical Medicine 40/2 (July 2023), 294-299.
JAMA Yılmaz D, Karagöz F. Concurrent expression of immunhistochemical parameters in breast cancer patients; clinical implications and consistency with Bloom-Richardson grading system. J. Exp. Clin. Med. 2023;40:294–299.
MLA Yılmaz, Dilek and Filiz Karagöz. “Concurrent Expression of Immunhistochemical Parameters in Breast Cancer Patients; Clinical Implications and Consistency With Bloom-Richardson Grading System”. Journal of Experimental and Clinical Medicine, vol. 40, no. 2, 2023, pp. 294-9.
Vancouver Yılmaz D, Karagöz F. Concurrent expression of immunhistochemical parameters in breast cancer patients; clinical implications and consistency with Bloom-Richardson grading system. J. Exp. Clin. Med. 2023;40(2):294-9.