Primer meme tümörleri ile karaciğer metastazları arasında ER, PR, HER2 ve Ki-67 ekspresyon uyumunun değerlendirilmesi: 57 olgunun retrospektif analizi

Abstract

Amaç: Bu çalışma, primer meme tümörleri ile karaciğer metastazları arasındaki östrojen reseptörü (ER), progesteron reseptörü (PR), insan epidermal büyüme faktörü reseptörü 2 (HER2) ve Ki-67 ekspresyonundaki değişiklikleri değerlendirmeyi amaçlamaktadır. Gereç ve yöntem: Meme kanseri karaciğer metastazı bulunan toplam 57 hasta çalışmaya dahil edilmiştir. Primer ve metastatik tümörlerde ER, PR, HER2 ve Ki-67 ekspresyonunu değerlendirmek için immünohistokimyasal boyama uygulanmıştır. Gerekli durumlarda HER2 durumu, silver in situ hibridizasyon (SISH) yöntemi ile doğrulanmıştır. Biyomarker ekspresyonundaki değişiklikleri değerlendirmek amacıyla istatistiksel analizler yapılmıştır. Bulgular: Primer ve metastatik biyopsiler arasındaki biyobelirteç ekspresyonları karşılaştırıldığında, 5 olguda ER durumunda değişiklik (1 olgu negatiften pozitife, 4 olgu pozitiften negatife), 22 olguda PR durumunda değişiklik (4 olgu negatiften pozitife, 18 olgu pozitiften negatife), 5 olguda HER2 durumunda değişiklik (2 olgu negatiften pozitife, 3 olgu pozitiften negatife) ve 13 olguda Ki-67 durumunda değişiklik (6 olgu düşükten yükseğe, 7 olgu yüksekten düşüğe) saptanmıştır. ER, PR, HER2 ve Ki-67 için diskordans oranları sırasıyla %8,8, %38,6, %8,8 ve %28,9 olarak hesaplanmıştır. Sonuç: Bulgularımız, primer ve metastatik meme kanseri lezyonları arasında biyobelirteç ekspresyonunda değişiklikler olabileceğini doğrulamaktadır. Reseptör durumunun tedavi kararlarındaki kritik rolü göz önünde bulundurulduğunda, metastatik lezyonlardan yeni biyopsi yapılması, kişiye özel tedavi planlamasında önemli bir yol gösterici olabilir.

Keywords

• Meme kanseri
• östrojen reseptörü
• progesteron reseptörü
• HER2
• diskordans

Evaluation of the concordance of ER, PR, HER2, and Ki-67 expression levels between primary breast tumors and their liver metastases: a retrospective analysis of 57 cases

Abstract

Purpose: This study aims to evaluate the changes in estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 expression between primary breast tumors and their liver metastases. Materials and methods: A total of 57 patients with breast cancer liver metastases were included. Immunohistochemical staining was performed to assess ER, PR, HER2, and Ki-67 expression in both primary and metastatic tumors. HER2 status was confirmed by silver in situ hybridization (SISH) when necessary. Statistical analyses were conducted to evaluate changes in biomarker expression. Results: Comparison of biomarker expression between primary and metastatic biopsies revealed changes in ER status in 5 cases (1 from negative to positive, 4 from positive to negative); PR status in 22 cases (4 from negative to positive, 18 from positive to negative); HER2 status in 5 cases (2 from negative to positive, 3 from positive to negative); and Ki-67 status in 13 cases (6 from low to high, 7 from high to low). The discordance rates for ER, PR, HER2, and Ki-67 were calculated as 8.8%, 38.6%, 8.8%, and 28.9%, respectively. Conclusion: Our findings confirm that biomarker expression may change between primary and metastatic breast cancer lesions. Given the crucial role of receptor status in treatment decisions, re-biopsy of metastatic lesions is essential to guide personalized therapy.

Keywords

• Breast cancer
• estrogen receptor
• progesterone receptor
• HER2
• discordance

References

1. Lin M, Jin Y, Lv H, Hu X, Zhang J. Incidence and prognostic significance of receptor discordance between primary breast cancer and paired bone metastases. Int J Cancer. 2023;152(7):1476-1489. doi:10.1002/ijc.34365
2. Peng L, Zhang Z, Zhao D, Zhao J, Mao F, Sun Q. Discordance in ER, PR, HER2, and Ki-67 Expression Between Primary and Recurrent/Metastatic Lesions in Patients with Primary Early Stage Breast Cancer and the Clinical Significance: Retrospective Analysis of 75 Cases. Pathol Oncol Res. 2021;27:599894. doi:10.3389/pore.2021.599894
3. Shanthala S, Amirtham U, Gopal C, N SM, Jacob L, Babu G. Study of Biomarker Discordance between Primary and Recurrent Sites and its Clinical Implications in Metastatic Breast Cancer: A Single Institutional Study from India. South Asian J. Cancer 2024;13(2):90-98. doi:10.1055/s-0043-1775807
4. Gogia A, Deo SVS, Sharma D, et al. Discordance in Biomarker Expression in Breast Cancer After Metastasis: Single Center Experience in India. J Glob Oncol. 2019;5:1-8. doi:10.1200/JGO.18.00184
5. Chen R, Qarmali M, Siegal GP, Wei S. Receptor conversion in metastatic breast cancer: analysis of 390 cases from a single institution. Modern Pathology. 2020;33(12):2499-2506. doi:10.1038/s41379-020-0615-z
6. Aurilio G, Disalvatore D, Pruneri G, et al. A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur J Cancer. 2014;50(2):277-289. doi:10.1016/j.ejca.2013.10.004
7. Schrijver WAME, Suijkerbuijk KPM, van Gils CH, van der Wall E, Moelans CB, van Diest PJ. Receptor conversion in distant breast cancer metastases: a systematic review and meta-analysis. J Natl Cancer Inst. 2018;110(6):568-580. doi:10.1093/jnci/djx273
8. Krøigård AB, Larsen MJ, Thomassen M, Kruse TA. Molecular Concordance Between Primary Breast Cancer and Matched Metastases. Breast J. 2016;22(4):420-430. doi:10.1111/tbj.12596

9. Rugo HS, Rumble RB, Macrae E, et al. Endocrine Therapy for Hormone Receptor-Positive Metastatic Breast Cancer: American Society of Clinical Oncology Guideline. J Clin Oncol. 2016;34(25):3069-3103. doi:10.1200/JCO.2016.67.1487
10. Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)†. Ann Oncol. 2018;29(8):1634-1657. doi:10.1093/annonc/mdy192
11. Duffy MJ, Harbeck N, Nap M, et al. Clinical use of biomarkers in breast cancer: Updated guidelines from the European Group on Tumor Markers (EGTM). Eur J Cancer. 2017;75:284-298. doi:10.1016/j.ejca.2017.01.017
12. Rosen PP, Menendez-Botet CJ, Urban JA, Fracchia A, Schwartz MK. Estrogen receptor protein (ERP) in multiple tumor specimens from individual patients with breast cancer. Cancer. 1977;39(5):2194-2200. doi:10.1002/1097-0142(197705)39:5<2194::aid-cncr2820390537>3.0.co;2-y
13. Pusztai L, Viale G, Kelly CM, Hudis CA. Estrogen and HER-2 receptor discordance between primary breast cancer and metastasis. Oncologist. 2010;15(11):1164-1168. doi:10.1634/theoncologist.2010-0059
14. Talmadge JE. Clonal selection of metastasis within the life history of a tumor. Cancer Res. 2007;67(24):11471-11475. doi:10.1158/0008-5472.CAN-07-2496
15. Suzuki M, Tarin D. Gene expression profiling of human lymph node metastases and matched primary breast carcinomas: clinical implications [published correction appears in Mol Oncol. 2008 Apr;1(4):440]. Mol Oncol. 2007;1(2):172-180. doi:10.1016/j.molonc.2007.03.005
16. Urquidi V, Sloan D, Kawai K, et al. Contrasting expression of thrombospondin-1 and osteopontin correlates with absence or presence of metastatic phenotype in an isogenic model of spontaneous human breast cancer metastasis. Clin Cancer Res. 2002;8(1):61-74
17. Dowsett M, Nielsen TO, A'Hern R, et al. Assessment of Ki-67 in breast cancer: recommendations from the International Ki-67 in Breast Cancer working group. J Natl Cancer Inst. 2011;103(22):1656-1664. doi:10.1093/jnci/djr393
18. Inwald EC, Klinkhammer-Schalke M, Hofstädter F, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 2013;139(2):539-552. doi:10.1007/s10549-013-2560-8
19. de Azambuja E, Cardoso F, de Castro G Jr, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96(10):1504-1513. doi:10.1038/sj.bjc.6603756