Meme Karsinomlarında ER, PR, c-erbB2, Ki67, E-Cadherin Ekspresyonları, Nottingham Histolojik Grade ve Bazı Klinik Parametreler Arasındaki İlişkilerin Değerlendirilmesi

Amaç: Bu çalışmada meme karsinomlarında Östrojen (ER), Progesteron (PR), c-erbB2 (HER2), Ki67, E-Cadherin ekspresyonları, Nottingham histolojik grade ve bazı klinik parametreler arasındaki ilişkilerin değerlendirilmesi amaçlanmıştır. Materyal ve Metot: Bu çalışmaya 2018-2019 yıllarında patoloji bölümümüzde meme karsinom tanısı alan toplam 74 hasta dahil edildi. İmmünohistokimyasal olarak çalışılan ER, PR, HER2, Ki67, E-Cadherin boyalı preparatlar retrospektif olarak değerlendirilip incelendi. ER ve PR için ≥%1 ekspresyon pozitif boyanma, <%1 ise negatif boyanma olarak kabul edildi. HER2 skor 0, 1, 2 veya 3 olarak değerlendirildi. Ki67 proliferasyon indeksi için <%10, %10-20, >%20 sırasıyla düşük, orta ve yüksek riskli olarak kabul edildi. Çalışmada elde edilen veriler ki-kare testi ile değerlendirildi. Bulgular: HER2 skoru ER durumuna göre istatistiksel olarak anlamlı değişim gösterdi (p=0,010). HER2 skoru PR durumuna göre de istatistiksel olarak anlamlı değişim gösterdi (p=0,004). Ki67 ile histolojik evre arasında anlamlı ilişki vardı (p<0.001). Sonuç: Meme karsinomlarında Ki67 indeksinin yüksek olması kötü prognostik göstergelerdendir. ER, PR ekspresyonunun saptanması ve HER2 ekspresyonunun saptanmaması ise iyi prognostik göstergelerdendir. Preanalitik ve analitik süreçler patologlar tarafından titizlikle takip edilmelidir.

Anahtar Kelimeler:

E-Cadherin, HER2, hormon reseptörleri, Ki67, meme karsinomu

Evaluation of the Relationships between ER, PR, c-erbB2, Ki67, E-Cadherin Expressions, Nottingham Histological Grade and some Clinical Parameters in Breast Carcinomas

Objective: In this study, it was aimed to evaluate the relationships between Estrogen receptor (ER), Progesterone receptor (PR), c-erbB2 (HER2), Ki67, E-Cadherin expressions, Nottingham histological grade and some clinical parameters in breast carcinomas. Materials and Methods: A total of 74 patients diagnosed with breast carcinoma (CA) in our pathology department between 2018-2019 were included in this study. Immunohistochemical preparations stained with ER, PR, HER2, Ki67 and E-Cadherin were evaluated and analyzed retrospectively. For ER and PR, ≥1% expression was considered as positive staining, and <1% was considered as negative staining. HER2 expression was scored as 0, 1, 2 and 3. Ki67 proliferation index was considered as low (<10%), intermediate (10-20%) and high risk (>20%). The data were analyzed with chi-square test. Results: HER2 score showed a statistically significant change according to ER status (p=0.010). HER2 score also showed a statistically significant change according to PR status (p=0.004). There was a significant correlation between Ki67 and histological stage (p<0.001). Conclusions: Detection of high Ki67 index in breast carcinomas is poor prognostic. Detection of ER and PR expression and no expression of HER2 are good prognostic indicators. Preanalytical and analytical processes should be followed meticulously by pathologists.

Keywords:

Breast Carcinoma, E-Cadherin, HER2, Hormone Receptors, Ki67,

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1. Collins LC, Marotti JD, Gelber S, et al. Pathologic features and molecular phenotype by patientage in a large cohort of young women with breast cancer. Breast Cancer ResTreat. 2012;131(3):1061-1066.
2. 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(5):403-410.
3. Robbins P, Pinder S, de Klerk N, et al. Histological grading of breast carcinomas: A study of interobserver agreement. Hum Pathol. 1995;26(8):873-879.
4. Hammond M, Hayes D, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists Guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridgedversion) Arch Pathol Lab Med. 2010;134(7):e48–e72
5. Davies C, Godwin J, Gray R, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793):771–784
6. Colleoni M, Viale G, Zahrieh D, et al. Chemotherapy is more effective in patients with breast cancer not expressing steroid hormone receptors: a study of preoperative treatment. Clin Cancer Res. 2004;10(19):6622-6628.
7. Viale G, Regan MM, Maiorano E, et al. Prognostic and predictive value of centrally reviewed expression of estrogen and progesterone receptors in a randomized trial comparing letrozole and tamoxifen adjuvant therapy for postmenopausal early breast cancer: BIG 1-98. J Clin Oncol. 2007;25(25):3846-3852.
8. Hammond MEH, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784-2095.
9. 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 Pathologist clinical practice guideline update. J Clin Oncol. 2013;31(31):3997-4013.
10. Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies— improving the management of early breast cancer: StGallen international expert consensus on the primary therapy of Early Breast Cancer 2015. Ann Oncol. 2015;26(8):1533-1546.
11. Walker RA, Camplejohn RS. Comparison of monoclonal antibody Ki-67 reactivity with grade and DNA flowcytometry of breast carcinomas. Br J Cancer. 1988; 57(3):281-283.
12. Kurbel S, Dmitrović B, Marjanović K, Vrbanec D, Juretić A. Distribution of Ki-67 values within HER2 &ER/PgR expression variants of ductal breast cancers as a potential link between IHC features and breast cancer biology. BMC Cancer. 2017;29;17(1):231.
13. Kraus JA, Dabbs DJ, Beriwal S, Bhargava R. Semi-quantitative immunohistochemical assay versus oncotype DX _ qRT-PCR assay for estrogen and progesterone receptors: an independent quality assurance study. Mod Pathol. 2012;25(6):869-876.
14. Perl AK, Wilgenbus P, Dahl U, Semb H, Christofori G. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature. 1998;392(6672):190–193.
15. Cheng CW, Wu PE, Yu JC, et al. Mechanisms of inactivation of E-cadherin in breast carcinoma: modification of the two-hit hypothesis of tumor suppressor gene. Oncogene. 2001;20(29):3814–3823.
16. Reed AEM, Kutasovic JR, Lakhani SR, Simpson PT. Invasive lobular carcinoma of the breast: morphology, biomarkers and ‘omics. Breast Cancer Res. 2015;17. doi:10.1186/s13058-015-0519-x
17. Wasif N, Maggard MA, Ko CY, Giuliano AE. Invasive lobular vs. ductal breast cancer: a stage-matched comparison of outcomes. Ann Surg Oncol. 2010;17(7):1862–1869.
18. Nofech-Mozes S, Vella ET, Dhesy-Thind S, et al. Systematic review on hormone receptor testing in breast cancer. Appl Immunohistochem Mol Morphol. 2012;20:(3):214-263.
19. Barnard ME, Boeke CE, Tamimi RM. Established breast cancer risk factors and risk of intrinsic tumor subtypes. Biochim Biophys Acta. 2015;1856(1):73–85.
20. Pai A, Baliga P, Shrestha BL. E-cadherin expression: a diag-nosticutility for differentiating breast carcinomas with ductal and lobular morphologies. J Clin Diagn Res. 2013;7(5):840-844.
21. Rakha EA, El-Sayed ME, Lee AHS, et al. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol. 2008,26(19):3153-3158
22. Ersöz C, Ergin M, Erdoğan Ş, Demircan O, Erkişi M. Evaluation of Ki-67/PCNA immunostaining in breast carcinoma and cytologic grading of fine needle aspirates of breast carcinoma: Correlation with histologic grade. Ann Med Res. 2002;11(1):13-16 23. Garimella V, Long ED, O’Kane SL, et al. Oestrogen and progesterone receptorstatus of individual foci in multifocal invasive ductal breast cancer. Acta Oncol. 2007;46(2):204-207.
24. Han G. ER, PR and HER2 testing in breast cancer. Diagnostic Histopathology. 2014;20(11):440-425.
25. Brown RW, Allred DC, et al. Prognostic significance and clinical- pathological correlations of celi cyclekinetics measured by Ki-67 immunocytochemistry in axillary node- negative carcinoma of the breast. Breast Cancer Res Treat. 1990;16:191.
26. Watkins E.J. Overview of breast cancer. Journal of the American Academy of Pas. 2019;32(10):13-17.
27. Xie F, Liu L, Yang H et al. The impact of reproductive factors on the risk of breast cancer by ER/PR and HER2: A multicenter case-control study in Northern and Eastern China. The Oncologist, 2022;27(1):e1–e8.
28. Bonacho T, Rodrigues F, Liberal J. Immunohistochemistry for diagnosis and prognosis of breast cancer: a review. Biotech Histochem. 2019;95(2):71-91
29. Cimino-Mathews A. Novel uses of immunohistochemistry in breast pathology: interpretation and pitfalls. Mod Pathol. 2021;34(1):62–77.
30. Perou CM, Sorlie T, Eisen MB, et al: Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-752.