İNVAZİV MEME KARSİNOMU TANILI OLGULARDA İMMÜNOHİSTOKİMYASAL YÖNTEMLE MOLEKÜLER SUBTİPLENDİRME VE SUBTİPLERİN PROGNOSTİK FAKTÖRLERLE İLİŞKİSİ

Öz

Bu çalışmada, kliniğimizde invaziv meme karsinom tanısı almış 79 olgunun retrospektif olarak immünohistokimyasal boyanma profillerinin analizini yapmak yolu ile moleküler alt tiplerinin belirlenmesi (lüminal A, lüminal B, human epidermal büyüme faktörü reseptörü 2 (HER2) eksprese eden, bazal-like ve null tip) ve bu subtiplerin prognostik faktörlerle ilişkisinin değerlendirilmesi amaçlandı. Tüm olgulara ait seçilmiş tümör bloklarında immünohistokimyasal olarak, ER, PR, HER2 ve CK5/6 ekspresyonları değerlendirildi. En sık görülen histolojik tip invaziv duktal karsinomdu. Lüminal A, en sık moleküler subtipti. Lüminal A’ların çoğunun grade’i II iken, bazal-like tümörlerin tamamı grade III olarak bulundu. Grade I olguların çoğu lüminal A tipindeydi. Olguların yarısına yakınında tanı anında tümör çapı 2-5cm arasındaydı. Literatürle uyumlu olarak, 2cm’den küçük tümör oranı lüminal A tipte fazlaydı. 2 adet medüller karsinom olgusu literatürle uyumlu olarak bazal-like tip olarak bulundu. Bazal-like grupta tümör derecesi diğer tiplere göre daha yüksekti. İstatiksel olarak moleküler subtipler ve prognostik faktörlerle anlamlı ilişki saptanmadı. 

Anahtar Kelimeler

• Meme Karsinomu,Moleküler Subtip,İmmünohistokimya,Prognoz

MOLECULAR SUBTYPING IN CASES DIAGNOSED AS INVASIVE BREAST CARCINOMA BY IMMUNOHISTOCHEMICAL METHOD AND THE RELATIONSHIP BETWEEN SUBTYPES AND PROGNOSTIC FACTORS

Abstract

      In this study, we analyzed retrospectively by immunohistochemical staining profiles of molecular subtyping of 79 invasive breast carcinomas in our clinic. It is aimed to evaluate the relation between prognostic factors and these subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) overexpressing, basal-like and null type). Immunohistochemically, ER, PR, HER2 and CK5/6 expressions were evaluated in selected tumor blocks of all cases. The most common histological type was invasive ductal carcinoma. Luminal A was the most frequent subtype. While most luminal A tumors were grade II, most basal-like tumors were grade III. The majority of grade I tumors were luminal A. Nearly half of the patients had tumors between 2-5cm in diameter at diagnosis. Similar to the literature, tumors rate smaller than 2cm was higher in luminal A type. 2 medullary carcinoma cases were consistent with the literature found in the basal-like type. In basal-like group, the tumor grade was higher than in other groups. Significant relationship was not found statistically between molecular subtypes and prognostic factors. 

Keywords

• Breast Carcinoma,Molecular Subtype,Immunohistochemistry,Prognosis

References

1. 1. Fadare, O. and Tavassoli, F.A., (2007). The Phenotypic Spectrum of Basal-Like Breast Cancer a Critical Appraisal. Adv Anat Pathol, 14:358-73.
2. 2. Tang, P., Skinner, K.A., and Hicks, D.G., (2009). Molecular Classification of Breast Carcinomas by Immunohistochemical Analysis: Are We Ready?. Diagn Mol Pathol, 18:125-32.
3. 3. Zhang, Y., Schnabel, C.A., Schroeder, B.E., Jerevall, P.L., Jankowitz, R.C., Fornander, T., et al., (2013). Breast Cancer Index Identifies Early-Stage Estrogen Receptor–Positive Breast Cancer Patients at Risk for Early and Late-Distant Recurrence. Clin Cancer Res, 19:4196-4205.
4. 4. Tamimi, R.M., Colditz, G.A., Hazra, A., Baer, H.J., Hankinson, S.E., Rosner, B., et al., (2012). Traditional Breast Cancer Risk Factors in Relation to Molecular Subtypes of Breast Cancer. Breast Cancer Res Treat, 131 159-167.
5. 5. Rakha, E. and Reis-Filho, J.S., (2009). Basal-Like Breast Carcinoma: From Expression Profiling to Routine Practice. Arch Pathol Lab Med, 133:860-8.
6. 6. Nielsen, T.O., Hsu, F.D., Jensen, K., Cheang, M., Karaca, G., Hu, Z., et al. ,(2004). Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma. Clin Cancer Res, 10:5367–74.
7. 7. Livas, C.A., Karaca, G., Nanda, R., Tretiakova, M.S., Olopade, O.I., Moore, D.T., et al., (2006). Phenotypic Evaluation of the Basal-Like Subtype of Invasive Breast Carcinoma. Mod Pathol, 19:264–71.
8. 8. Callagy, G., Cattaneo, E., Daigo, Y., Happerfield, L., Bobrow, L.G., Pharoah, P.D., et al., (2003). Molecular Classification of Breast Carcinomas Using Tissue Microarrays. Diagn Mol Pathol, 12:27–34.

9. 9. Sorlie, T., Perou, C.M., Tibshirani, R., Aas, T., Geisler, S., Johnsen, H., et al., (2001). Gene Expression Patterns of Breast Carcinomas Distinguish Tumor Subclasses with Clinical Implications. Proc Natl Acad Sci USA, 98:10869–74.
10. 10. Sorlie, T., Tibshirani, R., Parker, J., Hastie, T., Marron, J.S., Nobel, A., et al., (2003). Repeated Observation of Breast Tumor Subtypes in Independent Gene Expression Data Sets. Proc Natl Acad Sci USA, 100:8418–23.
11. 11. Ihemelandu, C.U., Leffall, L.D.J., Dewitty, R.L., Naab, T.J., Mezghebe, H.M., Makambi, K.H., et al., (2007). Molecular Breast Cancer Subtypes in Premenopausal and Postmenopausal African-American Women: Age-Specific Prevalence and Survival. J Surg Res, 143:109-18.
12. 12. Wiechmann, L., Sampson, M., Stempel, M., Jacks, L.M., Patil, S.M., King, T., et al., (2009). Presenting Features of Breast Cancer Differ by Molecular Subtype. Ann Surg Oncol, 16:2705-10.
13. 13. Zhao, J., Liu, H., Wang, M., Gu, L., Guo, X., Gu, F., et al., (2009). Characteristics and Prognosis for Molecular Breast Cancer Subtypes in Chinese Women. J Surg Oncol, 100:89–94.
14. 14. Matos, I., Dufloth, R., Alvarenga, M., Zeferino, L.C., and Schmitt, F., (2005). P63, Cytokeratin5, and Pcadherin: Three Molecular Markers to Distinguish Basal Phenotype in Breast Carcinomas. Virchows Arch, 447:688–94.
15. 15. Carey, L.A., Perou, C.M, Livasy, C.A., Dressler, L.G., Cowan, D., Conway, K., et al., (2006). Race, Breast Cancer Subtypes, and Survival in the Carolina Breast Cancer Study. Jama, 295:2492–502.
16. 16. Ge, Y., Sneige, N., Eltorky, M.A., Wang, Z., Lin, E., Gong, Y., et al., (2009). Immunohistochemical Characterization of Subtypes of Male Breast Carcinoma. Breast Cancer Res, 11:R28.
17. 17. Cheang, M.C., Chia, S.K., Voduc, D., Gao, D., Leung, S., Snider, J., et al., (2009). Ki67 Index, HER2 Status, and Prognosis of Patients with Luminal B Breast Cancer. J Natl Cancer Inst., 101: 736-50.
18. 18. Kim, M.J., Ro, J.Y., Ahn, S.H., Kim, H.H., Kim, S.B., and Gong, G., (2006). Clinicopathologic Significance of the Basal-Like Subtype of Breast Cancer: A Comparison with Hormone Receptor and Her2/Neu-Overexpressing Phenotypes. Hum Pathol, 37: 1217–26.
19. 19. Cheang, M.C., Voduc, D., Bajdik, C., Leung, S., McKinney, S., Chia, S.K., et al.,(2008). Basal-Like Breast Cancer Defined by Five Biomarkers Has Superior Prognostic Value than Triple-Negative Phenotype. Clin Cancer Res, 14: 1368–76.
20. 20. Liu, H., Fan, Q., Zhang, Z., Li, X., Yu, H., and Meng F., (2008). Basal-HER2 Phenotype Shows Poorer Survival than Basal-Like Phenotype in Hormone Receptor-Negative Invasive Breast Cancers. Hum Pathol, 39: 167–74.
21. 21. Abd El-Rehim, D.M., Pinder, S.E., Paish, C.E., Bell, J., Blamey, R.W., and Robertson, JF, et al.,(2004). Expression of Luminal and Basal Cytokeratins in Human Breast Carcinoma. J Pathol, 203: 661–71.
22. 22. Zhao, J., Liu, H., Wang, M., Gu, L., Guo, X., Gu, F., et al., (2009). Characteristics and Prognosis for Molecular Breast Cancer Subtypes in Chinese Women. J Surg Oncol, 100: 89–94.
23. 23. Dawood, S., Hu, R., Homes, M.D., Collins, L.C., Schnitt, S.J., Connolly, J., et al.,(2011). Defining Breast Cancer Prognosis Based on Molecular Subtypes: Results from a Large Cohort Study. Breast Cancer Res Treat, 126: 185-192.
24. 24. Caldarella, A., Buzzoni, C., Crotti, E., Bianchi, S., Vezzosi, V., Apicella, P., et al.,(2013). Invasive Breast Cancer: A Significant Correlation between Histological Types and Molecular Subgroups. J Cancer Res Clin Oncol, 139: 617-623.
25. 25. Andea, A.A., Bouwman, D., Wallis, T., and Visscher, D.W., (2004). Correlation of Tumor Volume and Surface Area with Lymph Node Status in Patients with Multifocal/Multicentric Breast Carcinoma. Cancer, 100: 20–7.
26. 26. Rakha, E.A., Putti, T.C., Abd El-Rehim, D.M., Paish, C., Green, A.R., Powe D.G., et al.,(2006). Morphological and Immunophenotypic Analysis of Breast Carcinomas with Basal and Myoepithelial Differentiation. J Pathol, 208: 495-506.
27. 27. Foulkes, W.D., Brunet, J.S., Stefansson, I.M., Straume, O., Chappuis, P.O., Begin, L.R., et al., (2004). The Prognostic Implication of the Basal-Like (Cyclin E High/P27 Low/P53+/Glomeruloid-Microvascular-Proliferation+) Phenotype of BRCA1- Related Breast Cancer. Cancer Res, 64: 830-5.
28. 28. Rodriguez-Pinilla, S.M., Sarrio, D., Honrado, E., Moreno-Bueno, G., Hardisson, D., Calero, F., et al., (2007). Vimentin and Laminin Expression is Associated with Basal-Like Phenotype in both Sporadic and BRCA1-Associated Breast Carcinomas. J Clin Pathol, 60: 1006-12.
29. 29. Bertucci, F., Finetti, P., Cervera, N., Charafe-Jauffret, E., Mamessier, E., Adelaide, J., et al., (2006). Gene Expression Profiling Shows Medullary Breast Cancer is a Subgroup of Basal Breast Cancers. Cancer Res, 66: 4636-44.
30. 30. Calza, S., Hall, P,., Auer, G., Bjohle, J., Klaar, S., Kronenwett, U, et al., (2006). Intrinsic Molecular Signature of Breast Cancer in a Population-Based Cohort of 412 Patients. Breast Cancer Res, 8: R34.
31. 31. Munja, K., Ambaye, A., Evans, M.F., Mitchell, J., Nandedkar, S., and Cooper, K., (2009). Immunohistochemical Analysis of ER, PR, HER2 and CK5/6 in Infiltrative Breast Carcinomas in Indian Patients. Asian Pacific J Cancer Prev, 10: 773-778
32. 32. Brenton, J.D., Carey, L.A., Ahmed, A,.A., and Caldas, C.,(2005). Molecular Classification and Molecular Forecasting of Breast Cancer: Ready for Clinical Application? J Clin Oncol, 23: 7350–60.