Meme Kanserinde Moleküler Alt Tiplerin Klinikopatolojik Özelliklerle İlişkisi

Öz

Amaç: Meme kanserinde, moleküler alt tiplerin, klinikopatolojik özellikler (tanı yaşı, histolojik tip, histolojik derece, pT ve pN evreleri)  ile ilişkilerinin tespit edilmesi amaçlanmıştır.

Gereç ve Yöntem: Çalışma grubu 194 kadın meme kanseri içermekteydi. Süleyman Demirel Üniversitesi Tıp Fakültesi Tıbbi Patoloji Anabilim Dalı arşivi taranarak 2010-2015 yılları arasında meme kanseri tanısı verilmiş olgulara ait biyopsi ve radikal meme rezeksiyonu materyallerinin preparatları tekrar incelendi. Olguların immünhistokimyasal ER, PgR, HER2 ve Ki67 boyalı preparatları tekrar değerlendirilerek moleküler alt tiplendirme yapıldı.

Bulgular: Tümör moleküler alt tipleri; %47,4 olguda Luminal A [ER ve/veya PgR(+)/HER2(-)/Ki67 ≤ %14], %25,8 olguda Luminal B [ER ve/veya PgR(+)/HER2(+) veya (-) /Ki67 > %14], %13,4 olguda HER2 overeksprese [ER(-)/PgR(-)/HER2(+)] ve %13,4 olguda ise üçlü negatif [ER(-)/PgR(-)/HER2(-)] idi. Tümör derecesi ve aksiller lenf nodu metastazı; Luminal B, HER2 overeksprese ve üçlü negatif tümörlerde Luminal A tümörlere göre daha yüksek izlendi. Luminal tip tümörlerle karşılaştırıldığında, HER2 overeksprese ve üçlü negatif tümörlerde lenfovasküler invazyon oranı anlamlı olarak daha fazla idi.

Sonuç: Heterojen bir tümör grubu olan meme kanserlerinde evre ve diğer iyi bilinen klinikopatolojik özelliklerin yanında moleküler alt tiplendirmenin de hasta yönetimi için faydalı bilgiler verebileceği sonucuna varılmıştır.

Anahtar Kelimeler

• Meme,kanser,moleküler alt tip,immünhistokimya

The relationship of the molecular subtypes with the clinicopathological features in breast cancer

Öz

Objective: To determine the relationship between the molecular subtypes and the clinicalopathological features (age at the diagnosis, histological type, histological grade, pT and pN stages) in breast cancer.

Materials and Methods: The study population included 194 women with breast carcinoma, who were diagnosed between 2010 and 2015. The slides of the cases in the archive of the Süleyman Demirel University Faculty of Medicine Department of Pathology were reevaluated. Immunohistochemical ER, PgR, HER2 and Ki67 stained slides were used to perform the molecular subtyping.

Results: Among the cases molecular subtypes were; Luminal A [ER and/or PgR(+)/HER2(-)/Ki67 ≤ 14%] in 47.4% of cases,  Luminal B [ER and/or PgR(+)/HER2(+) or (-) /Ki67 > 14%] in 25.8% of cases, HER2 overexpressing [ER(-)/PgR(-)/HER2(+)] in 13.4% of cases, and triple negative [ER(-)/PgR(-)/HER2(-)] in 13.4% of the cases, respectively. Tumor grade and axillary lymph node metastasis in Luminal B, HER2 overexpressing and triple negative tumors were significantly higher than they were in Luminal A tumors. Lymphovascular invasion rate was significantly higher in HER2 overexpressing and triple negative tumors compared to Luminal type tumors.

Conclusions: It was concluded that the molecular subtyping of the breast carcinoma, which is a heterogeneous tumor group, can give important information for the management of the cases along with the stage and other well-known clinicopathological features.

Anahtar Kelimeler

• Breast,cancer,molecular subtype,immunohistochemistry

Kaynakça

1. Petersen NV, Ramskov S, Andersen RS, Met Ö, Straten PT, Bentzen AKK, et al. T-cell recognition of breast cancer antigens. Proceedings of the 4th CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2):Ab.nr B036.
2. Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G, et al. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res 2008;14(16):15.
3. Prat A , Pineda E,Adamo B, Galván P, Fernández A, Gaba L, et al. Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast 2015;24(2):26-35.
4. Dias K, Dvorkin-Gheva A, Hallett RM, Wu Y, Hassell J, Pond GR, et al. Claudin-Low Breast Cancer; Clinical & Pathological Characteristics. PLoS One. 2017;12(1):e0168669.
5. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ. Strategies for subtypes-dealing with the diversity of breastcancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2011. Annals of Oncology 2011;22:1736-1747.
6. Yersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol. 2014;5(3):412-424.
7. Ni YB, Tsang JY, Chan SK, Tse GM. A novel morphologic-molecular recurrence predictive model refines traditional prognostic tools for invasive breast carcinoma. Ann Surg Oncol. 2014;9:2928-2933
8. Tenea-Cojan TS, Georgescu CV, Corici OM, Voinea B, Georgescu DM, Vidrighin C, et al. Histopathological study on conservatively operated breast carcinomas. Curr Health Sci J. 2016;42(3):269-282.

9. Jönsson G, Staaf J, Vallon-Christersson J, Ringnér M, Holm K, Hegardt C, et al. Genomic subtypes of breast cancer identified by array-comparative genomic hybridization display distinct molecular and clinical characteristics. Breast Cancer Res. 2010;12(3):R42.
10. Cherbal F, Gaceb H, Mehemmai C, Saiah I, Bakour R, Rouis AO, et al. Distribution of molecular breast cancer subtypes among Algerian women and correlation with clinical and tumor characteristics: a population-based study. Breast Dis. 2015;35(2):95-102.
11. Chu KC, Anderson WF, Fritz A, Ries LA, Brawley OW. Frequency distributions of breast cancer characteristics classified by estrogen receptor and progesterone receptor status for eight racial/ethnic groups. Cancer 2001;1:37-45.
12. Kamranzadeh H, Ardekani RM, Kasaeian A, Sadighi S, Maghsudi S, Jahanzad I, et al. Association between Ki-67 expression and clinicopathological features in prognosis of breast cancer: A retrospective cohort study. J Res Med Sci 2019;24:30.
13. Nishimukai A, Yagi T, Yanai A, Miyagawa Y, Enomoto Y, Murase K, et al. High Ki-67 Expression and low progesterone receptor expression could ındependently lead to a worse prognosis for postmenopausal patients with estrogen receptor-positive and HER2-negative breast cancer. Clin Breast Cancer 2015;15(3):204-211.
14. Caldarella A, Buzzoni C, Crocetti E, Bianchi S, Vezzosi V, Apicella P, et al. Invasive breast cancer: a significant correlation between histological types and molecular subgroups. J Cancer Res Clin Oncol 2013;139(4):617-623.
15. Garrido-Castro AC, Lin NU, Polyak K. Insights into Molecular Classifi cations of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment, American Association for Cancer Research, 2019;doi: 10.1158/2159-8290.CD-18-1177.
16. Van Calster B, Vanden Bempt I, Drijkoningen M, Pochet N, Cheng J, Van Huffel S, et al. Axillary lymph node status of operable breast cancers by combined steroid receptor and HER2 status: triple positive tumours are more likely lymph node positive. Breast Cancer Res Treat 2009;113(1):181-187.
17. Kim MJ, Ro JY, Ahn SH, Kim HH, Kim SB, Gong G. Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/neu-overexpressing phenotypes. Hum Pathol 2006;37(9):1217-1226.