Üçlü Negatif Meme Kanserlerinde İmmünohistokimyasal PD-L1 ve Androjen Reseptörü Ekspresyonlarının Klinikopatolojik Önemi
Öz
Amaç: Meme kanserlerinin bir alt kümesi olan Triple Negatif Meme Kanserleri (TNBC) yüksek derecelidir ve genç yaşta ortaya çıkar. Daha sık nüks ve metastaz ve daha kötü prognoz ile ilişkilidir. Günümüzde meme kanseri ve bağışıklık sistemi arasında dinamik bir etkileşim olduğuna dair kanıtlar artmaktadır. Luminal Androjen Reseptörü (LAR) alt tipi, Androjen Reseptörü (AR) sinyaline bağlıdır ve hedefe yönelik terapötiklerin geliştirilmesi için bir fırsat sunan farklı bir prognoza sahip yeni bir TNBC alt tipini temsil eder. Bu çalışmada, TNBC' de Programlı ölüm ligandı 1 (PD-L1) ve AR' nin immünohistokimyasal ekspresyonunu ve bunların klinik parametrelerle korelasyonunu araştırmayı amaçladık.
Gereç ve Yöntemler: Bu çalışmaya 2013-2019 yılları arasında Aydın Adnan Menderes Üniversitesi Tıp Fakültesi Hastanesi Patoloji Anabilim Dalı'nda cerrahi materyalden primer TNBC tanısı alan 64 hasta dahil edildi. Demografik ve histopatolojik özellikler arşiv raporlarından elde edildi. Bloklardan hazırlanan kesitlere PD-L1 ve AR immünhistokimyasal boyaları uygulandı.
Bulgular: Ortalama yaş 53,47±15,044 (28-84 yıl) idi. PD-L1 pozitifliği %57,8 ve AR pozitifliği %26,6 idi. PD-L1 pozitifliği ile Ki67 proliferasyon indeksi (p=0,009) ve lenfovasküler invazyon (p=0,009) arasında anlamlı bir korelasyon vardı ve PD-L1 ile diğer parametreler arasında korelasyon yoktu. AR ve klinikopatolojik parametreler arasında anlamlı ilişki saptanmadı.
Sonuç: PD-L1 ve AR TNBC için önemli prognostik belirteçlerdir ve hedefe yönelik tedaviler için önemli grupları tanımlamaktadır. Çalışmamızda PD-L1 pozitif olgular kötü prognostik belirteçlerle ilişkilidir ve her iki belirteç için daha geniş gruplarda ileri çalışmalara ihtiyaç vardır.
Anahtar Kelimeler
Proje Numarası
TTF-18032
Kaynakça
- 1. Zhao S, Ma D, Xiao Y, Li XM, Ma JL, Zhang H, Xu XL, Lv H, Jiang WH, Yang WT, Jiang YZ, Zhang QY, Shao ZM. Molecular Subtyping of Triple-Negative Breast Cancers by Immunohistochemistry: Molecular Basis and Clinical Relevance. Oncologist. 2020;25(10):e1481-e91.
- 2. Author AB AC, Author EF. WHO Classification of Tumours Editorial Board. Breast tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2019. Available from: https://tumourclassification.iarc.who.int/chapters/32.
- 3. Lehmann BD, Jovanović B, Chen X, Estrada MV, Johnson KN, Shyr Y, Moses HL, Sanders ME, Pietenpol JA. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection. PloS one. 2016;11(6):e0157368.
- 4. Li F, Ren Y, Wang Z. Programmed death 1 Ligand 1 expression in breast cancer and its association with patients' clinical parameters. Journal of cancer research and therapeutics. 2018;14(1):150-4.
- 5. Muenst S, Schaerli A, Gao F, Däster S, Trella E, Droeser R, Muraro M, Zajac P, Zanetti R, Gillanders W. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast cancer research and treatment. 2014;146:15-24.
- 6. Angelico G, Broggi G, Tinnirello G, Puzzo L, Vecchio GM, Salvatorelli L, Memeo L, Santoro A, Farina J, Mulé A. Tumor infiltrating lymphocytes (TILS) and PD-L1 expression in breast cancer: a review of current evidence and prognostic implications from pathologist’s perspective. Cancers. 2023;15(18):4479.
- 7. Rampurwala M, Wisinski KB, O’Regan R. Role of the androgen receptor in triple-negative breast cancer. Clinical advances in hematology & oncology: H&O. 2016;14(3):186.
- 8. Erdoğdu İH, Gürel D. Evaluation of Somatic PIK3CA Mutations Detected by Next-generation Sequencing in Breast Cancer Cases. Meandros Medical & Dental Journal. 2023;24(4).
- 9. Erdogdu IH, Orenay-Boyacioglu S, Boyacioglu O, Gurel D, Akdeniz N, Meteoglu I. Variation Analysis in Premenopausal and Postmenopausal Breast Cancer Cases. Journal of Personalized Medicine. 2024;14(4):434.
- 10. Vagia E, Mahalingam D, Cristofanilli M. The Landscape of Targeted Therapies in TNBC. Cancers (Basel). 2020;12(4).
- 11. Medić-Milijić N, Jovanić I, Nedeljković M, Marković I, Spurnić I, Milovanović Z, Ademović N, Tomić T, Tanić N, Tanić N. Prognostic and Clinical Significance of PD-L1, EGFR and Androgen Receptor (AR) Expression in Triple-Negative Breast Cancer (TNBC) Patients. Life (Basel). 2024;14(6).
- 12. Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, Su X, Wang Y, Gonzalez-Angulo AM, Akcakanat A. PD-L1 expression in triple-negative breast cancer. Cancer immunology research. 2014;2(4):361-70.
- 13. Tung N, Garber JE, Hacker MR, Torous V, Freeman GJ, Poles E, Rodig S, Alexander B, Lee L, Collins LC, Schnitt SJ. Prevalence and predictors of androgen receptor and programmed death-ligand 1 in BRCA1-associated and sporadic triple-negative breast cancer. NPJ Breast Cancer. 2016;2:16002.
- 14. Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, Bossuyt V, Pusztai L, Lannin DR, Rimm DL. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunol Res. 2015;3(4):326-32.
- 15. Stovgaard ES, Dyhl-Polk A, Roslind A, Balslev E, Nielsen D. PD-L1 expression in breast cancer: expression in subtypes and prognostic significance: a systematic review. Breast cancer research and treatment. 2019;174:571-84.
- 16. Botti G, Collina F, Scognamiglio G, Rao F, Peluso V, De Cecio R, Piezzo M, Landi G, De Laurentiis M, Cantile M, Di Bonito M. Programmed Death Ligand 1 (PD-L1) Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients. Int J Mol Sci. 2017;18(2).
- 17. Bae SB, Cho HD, Oh MH, Lee JH, Jang SH, Hong SA, Cho J, Kim SY, Han SW, Lee JE, Kim HJ, Lee HJ. Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer. J Breast Cancer. 2016;19(3):242-51.
- 18. Dubrava AL, Kyaw PSP, Newman J, Pringle J, Westhuyzen J, La Hera Fuentes G, Shakespeare TP, Sakalkale R, Aherne NJ. Androgen Receptor Status in Triple Negative Breast Cancer: Does It Correlate with Clinicopathological Characteristics? Breast Cancer (Dove Med Press). 2023;15:359-71.
- 19. Rampurwala M, Wisinski KB, O'Regan R. Role of the androgen receptor in triple-negative breast cancer. Clin Adv Hematol Oncol. 2016;14(3):186-93.
- 20. Gerratana L, Basile D, Buono G, De Placido S, Giuliano M, Minichillo S, Coinu A, Martorana F, De Santo I, Del Mastro L, De Laurentiis M, Puglisi F, Arpino G. Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype. Cancer Treat Rev. 2018;68:102-10.
- 21. Prutianu I, Giuşcă SE, Gafton B, Chifu MB, Terinte C, Antonescu A, Popovici L, Căruntu ID. Triple-negative breast cancer: from classical clinicopathological features to androgen receptor profile. Rom J Morphol Embryol. 2024;65(2):209-16.
- 22. Zakaria F, El-Mashad N, Mohamed D. Androgen receptor expression as a prognostic and predictive marker in triple-negative breast cancer patients. Alexandria journal of medicine. 2016;52(2):131–40-–40.
- 23. Payandeh M, Shazad B, Madani S, Ramezani M, Sadeghi M. Androgen Receptor Expression and its Correlation with Other Risk Factors in Triple Negative Breast Cancers: a Report from Western Iran. Asian Pac J Cancer Prev. 2016;17(7):3321-4.
- 24. Lyalkin SA, Verevkina NO, Alekseyenko OO, Syvak LA. Prognostic role of androgen receptor expression in patients with metastatic triple negative breast cancer. Exp Oncol. 2020;42(2):140-3.
- 25. Jam S, Abdollahi A, Zand S, Khazaeipour Z, Omranipour R, Najafi M. Androgen Receptor Expression in Triple-Negative Breast Cancer. Archives of Breast Cancer. 2019:92-5. Available from: https://www.archbreastcancer.com/index.php/abc/article/view/249.
- 26. Adamo B, Ricciardi GRR, Ieni A, Franchina T, Fazzari C, Sanò MV, Angelico G, Michele C, Tuccari G, Adamo V. The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer. Oncotarget. 2017;8(44):76974.
- 27. Teoh PY, Tan GC, Mahsin H, Wong YP. Androgen receptor expression in triple negative breast carcinoma and its association with the clinicopathological parameters. Malays J Pathol. 2019;41(2):125-32.
- 28. Riaz N, Idress R, Habib S, Lalani EN. Lack of Androgen Receptor Expression Selects for Basal-Like Phenotype and Is a Predictor of Poor Clinical Outcome in Non-Metastatic Triple Negative Breast Cancer. Front Oncol. 2020;10:1083.
- 29. Sunar V, Dogan HT, Sarici F, Ates O, Akin S, Baspinar B, Aksoy S, Altundag K. Association between androgen receptor status and prognosis in triple negative breast cancer. J BUON. 2018;23(5):1325-30.
- 30. Liu Y-X, Zhang K-J, Tang L-L. Clinical significance of androgen receptor expression in triple negative breast cancer-an immunohistochemistry study. Oncology letters. 2018;15(6):10008-16.
- 31. Cabezas-Quintario M, Zenzola V, Arguelles M, Perez-Fernandez E. Androgen receptor as prognostic marker in triple-negative breast cancer patients. J Med Surg Pathol. 2018;3(4):1-6.
- 32. Astvatsaturyan K, Yue Y, Walts AE, Bose S. Androgen receptor positive triple negative breast cancer: Clinicopathologic, prognostic, and predictive features. PLoS One. 2018;13(6):e0197827.
- 33. Asano Y, Kashiwagi S, Goto W, Tanaka S, Morisaki T, Takashima T, Noda S, Onoda N, Ohsawa M, Hirakawa K. Expression and clinical significance of androgen receptor in triple-negative breast cancer. Cancers. 2017;9(1):4.
Clinicopathological Significance of Immunohistochemical PD-L1 and Androgen Receptor Expressions in Triple Negative Breast Cancers
Öz
Objective:
Triple negative breast cancers(TNBC), a subset of breast cancers, despite the wide range of morphologies, are high-grade, and related to younger age, higher incidence of metastases, higher risk of recurrence and poorer prognosis. Currently, there is increasing evidence of a dynamic interaction between the immune system and breast cancer. Additionally, the Luminal Androgen Receptor(LAR) subtype, one of the four subtypes of TNBC, is dependent on Androgen Receptor(AR) signaling, and represents a novel subtype of TNBC with a distinct prognosis that offers an opportunity for the development of targeted therapeutics. In this study, we aimed to investigate the immunohistochemical expression of Programmed death ligand 1(PD-L1) and AR and their correlations with clinical parameters in TNBC and to determine the groups suitable for targeted therapy.
Materials and Methods:
Sixtyfour patients who received a primary diagnosis of TNBC from surgical material at Aydın Adnan Menderes University between 2013-2019 were available for this study. Demographic and histopathological characteristics were obtained from archival reports. PD-L1 and AR immunohistochemical stains were applied to sections prepared from the blocks.
Results:
The mean age was 53,47±15,044(range 28-84 years). The percentage of PD-L1 positivity was %57,8 and AR positivity was %26,6. There was a significant correlation PD-L1 positivity with Ki67 proliferation index(p=0.009), and lymphovascular invasion(p=0.009) and no correlation between PD-L1 and other parameters.
Conclusion:
PD-L1 and AR are important prognostic markers for TNBC and identify important groups for targeted therapies. PD-L1 positive cases are associated with poor prognostic markers and further studies in larger groups are needed for both markers.
Anahtar Kelimeler
Triple negative breast cancer PD-L1 AR Ki67 immunohistochemistry
Etik Beyan
This study was approved by the Ethics Committee for Noninvasive Clinical Trials of Aydın Adnan Menderes University, Approval number 2018/1343.
Proje Numarası
TTF-18032
Kaynakça
- 1. Zhao S, Ma D, Xiao Y, Li XM, Ma JL, Zhang H, Xu XL, Lv H, Jiang WH, Yang WT, Jiang YZ, Zhang QY, Shao ZM. Molecular Subtyping of Triple-Negative Breast Cancers by Immunohistochemistry: Molecular Basis and Clinical Relevance. Oncologist. 2020;25(10):e1481-e91.
- 2. Author AB AC, Author EF. WHO Classification of Tumours Editorial Board. Breast tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2019. Available from: https://tumourclassification.iarc.who.int/chapters/32.
- 3. Lehmann BD, Jovanović B, Chen X, Estrada MV, Johnson KN, Shyr Y, Moses HL, Sanders ME, Pietenpol JA. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection. PloS one. 2016;11(6):e0157368.
- 4. Li F, Ren Y, Wang Z. Programmed death 1 Ligand 1 expression in breast cancer and its association with patients' clinical parameters. Journal of cancer research and therapeutics. 2018;14(1):150-4.
- 5. Muenst S, Schaerli A, Gao F, Däster S, Trella E, Droeser R, Muraro M, Zajac P, Zanetti R, Gillanders W. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast cancer research and treatment. 2014;146:15-24.
- 6. Angelico G, Broggi G, Tinnirello G, Puzzo L, Vecchio GM, Salvatorelli L, Memeo L, Santoro A, Farina J, Mulé A. Tumor infiltrating lymphocytes (TILS) and PD-L1 expression in breast cancer: a review of current evidence and prognostic implications from pathologist’s perspective. Cancers. 2023;15(18):4479.
- 7. Rampurwala M, Wisinski KB, O’Regan R. Role of the androgen receptor in triple-negative breast cancer. Clinical advances in hematology & oncology: H&O. 2016;14(3):186.
- 8. Erdoğdu İH, Gürel D. Evaluation of Somatic PIK3CA Mutations Detected by Next-generation Sequencing in Breast Cancer Cases. Meandros Medical & Dental Journal. 2023;24(4).
- 9. Erdogdu IH, Orenay-Boyacioglu S, Boyacioglu O, Gurel D, Akdeniz N, Meteoglu I. Variation Analysis in Premenopausal and Postmenopausal Breast Cancer Cases. Journal of Personalized Medicine. 2024;14(4):434.
- 10. Vagia E, Mahalingam D, Cristofanilli M. The Landscape of Targeted Therapies in TNBC. Cancers (Basel). 2020;12(4).
- 11. Medić-Milijić N, Jovanić I, Nedeljković M, Marković I, Spurnić I, Milovanović Z, Ademović N, Tomić T, Tanić N, Tanić N. Prognostic and Clinical Significance of PD-L1, EGFR and Androgen Receptor (AR) Expression in Triple-Negative Breast Cancer (TNBC) Patients. Life (Basel). 2024;14(6).
- 12. Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, Su X, Wang Y, Gonzalez-Angulo AM, Akcakanat A. PD-L1 expression in triple-negative breast cancer. Cancer immunology research. 2014;2(4):361-70.
- 13. Tung N, Garber JE, Hacker MR, Torous V, Freeman GJ, Poles E, Rodig S, Alexander B, Lee L, Collins LC, Schnitt SJ. Prevalence and predictors of androgen receptor and programmed death-ligand 1 in BRCA1-associated and sporadic triple-negative breast cancer. NPJ Breast Cancer. 2016;2:16002.
- 14. Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, Bossuyt V, Pusztai L, Lannin DR, Rimm DL. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer. Cancer Immunol Res. 2015;3(4):326-32.
- 15. Stovgaard ES, Dyhl-Polk A, Roslind A, Balslev E, Nielsen D. PD-L1 expression in breast cancer: expression in subtypes and prognostic significance: a systematic review. Breast cancer research and treatment. 2019;174:571-84.
- 16. Botti G, Collina F, Scognamiglio G, Rao F, Peluso V, De Cecio R, Piezzo M, Landi G, De Laurentiis M, Cantile M, Di Bonito M. Programmed Death Ligand 1 (PD-L1) Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients. Int J Mol Sci. 2017;18(2).
- 17. Bae SB, Cho HD, Oh MH, Lee JH, Jang SH, Hong SA, Cho J, Kim SY, Han SW, Lee JE, Kim HJ, Lee HJ. Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer. J Breast Cancer. 2016;19(3):242-51.
- 18. Dubrava AL, Kyaw PSP, Newman J, Pringle J, Westhuyzen J, La Hera Fuentes G, Shakespeare TP, Sakalkale R, Aherne NJ. Androgen Receptor Status in Triple Negative Breast Cancer: Does It Correlate with Clinicopathological Characteristics? Breast Cancer (Dove Med Press). 2023;15:359-71.
- 19. Rampurwala M, Wisinski KB, O'Regan R. Role of the androgen receptor in triple-negative breast cancer. Clin Adv Hematol Oncol. 2016;14(3):186-93.
- 20. Gerratana L, Basile D, Buono G, De Placido S, Giuliano M, Minichillo S, Coinu A, Martorana F, De Santo I, Del Mastro L, De Laurentiis M, Puglisi F, Arpino G. Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype. Cancer Treat Rev. 2018;68:102-10.
- 21. Prutianu I, Giuşcă SE, Gafton B, Chifu MB, Terinte C, Antonescu A, Popovici L, Căruntu ID. Triple-negative breast cancer: from classical clinicopathological features to androgen receptor profile. Rom J Morphol Embryol. 2024;65(2):209-16.
- 22. Zakaria F, El-Mashad N, Mohamed D. Androgen receptor expression as a prognostic and predictive marker in triple-negative breast cancer patients. Alexandria journal of medicine. 2016;52(2):131–40-–40.
- 23. Payandeh M, Shazad B, Madani S, Ramezani M, Sadeghi M. Androgen Receptor Expression and its Correlation with Other Risk Factors in Triple Negative Breast Cancers: a Report from Western Iran. Asian Pac J Cancer Prev. 2016;17(7):3321-4.
- 24. Lyalkin SA, Verevkina NO, Alekseyenko OO, Syvak LA. Prognostic role of androgen receptor expression in patients with metastatic triple negative breast cancer. Exp Oncol. 2020;42(2):140-3.
- 25. Jam S, Abdollahi A, Zand S, Khazaeipour Z, Omranipour R, Najafi M. Androgen Receptor Expression in Triple-Negative Breast Cancer. Archives of Breast Cancer. 2019:92-5. Available from: https://www.archbreastcancer.com/index.php/abc/article/view/249.
- 26. Adamo B, Ricciardi GRR, Ieni A, Franchina T, Fazzari C, Sanò MV, Angelico G, Michele C, Tuccari G, Adamo V. The prognostic significance of combined androgen receptor, E-Cadherin, Ki67 and CK5/6 expression in patients with triple negative breast cancer. Oncotarget. 2017;8(44):76974.
- 27. Teoh PY, Tan GC, Mahsin H, Wong YP. Androgen receptor expression in triple negative breast carcinoma and its association with the clinicopathological parameters. Malays J Pathol. 2019;41(2):125-32.
- 28. Riaz N, Idress R, Habib S, Lalani EN. Lack of Androgen Receptor Expression Selects for Basal-Like Phenotype and Is a Predictor of Poor Clinical Outcome in Non-Metastatic Triple Negative Breast Cancer. Front Oncol. 2020;10:1083.
- 29. Sunar V, Dogan HT, Sarici F, Ates O, Akin S, Baspinar B, Aksoy S, Altundag K. Association between androgen receptor status and prognosis in triple negative breast cancer. J BUON. 2018;23(5):1325-30.
- 30. Liu Y-X, Zhang K-J, Tang L-L. Clinical significance of androgen receptor expression in triple negative breast cancer-an immunohistochemistry study. Oncology letters. 2018;15(6):10008-16.
- 31. Cabezas-Quintario M, Zenzola V, Arguelles M, Perez-Fernandez E. Androgen receptor as prognostic marker in triple-negative breast cancer patients. J Med Surg Pathol. 2018;3(4):1-6.
- 32. Astvatsaturyan K, Yue Y, Walts AE, Bose S. Androgen receptor positive triple negative breast cancer: Clinicopathologic, prognostic, and predictive features. PLoS One. 2018;13(6):e0197827.
- 33. Asano Y, Kashiwagi S, Goto W, Tanaka S, Morisaki T, Takashima T, Noda S, Onoda N, Ohsawa M, Hirakawa K. Expression and clinical significance of androgen receptor in triple-negative breast cancer. Cancers. 2017;9(1):4.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Patoloji |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Proje Numarası | TTF-18032 |
| Erken Görünüm Tarihi | 22 Haziran 2025 |
| Yayımlanma Tarihi | 23 Haziran 2025 |
| Gönderilme Tarihi | 30 Ocak 2025 |
| Kabul Tarihi | 7 Nisan 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 26 Sayı: 2 |
