Meme Karsinomlarında Nükleer Morfometrinin Klinikopatolojik Prognostik Parametreler ve İmmünohistokimyasal ER, PR ve Cerb-B2 Ekspresyonları ile İlişkisi

Yıl 2021, , 95 - 102, 25.08.2021

Murat Çelik , Zeliha Çelik , Pınar Karabağlı Ceyhan Uğurluoğlu Serdar Altınay , Özlem Yavaş Ata

https://doi.org/10.46332/aemj.882653

Öz

Amaç: Bilgisayarlı histomorfometrik analiz, meme karsinomlarını da içeren pek çok tümörün ayırıcı tanısında kullanılan bir araç olup, malign tümörlerin derecelendirmesinde, prognoz ve tedavi yanıtının değerlendirilmesinde de denenmiştir. Bu çalışmada meme karsinomlarında nükleer morfometrik değişkenler ile klinikopatolojik prognostik parametreler ve immünohistokimyasal ER, PR, Cerb-B2 ekspresyonları arasındaki ilişkiyi araştırmak amaçlanmıştır.

Araçlar ve Yöntem: Çalışmada meme karsinomu tanısı alan 105 olguda, ortalama nükleus alanı (ONA), ortalama nükleus çevresi (ONÇ), ortalama nükleus uzun çapı (ONUÇ) ve ortalama nükleus kısa çapı (ONKÇ) dahil olmak üzere çeşitli nükleer morfometrik parametreler açısından değerlendirildi. Dijital görüntü analiz sistemi kullanılarak Hematoksilen-eosin ile boyanmış lamlar üzerinde, lezyon başına elli tümör hücre çekirdeğinde ölçümler yapıldı. Elde edilen veriler ile klinikopatolojik prognostik parametreler arasındaki ilişki istatistiksel yöntemler ile değerlendirildi.

Bulgular: Histolojik gruplar arasında, invaziv duktal karsinomada (IDK), diğer tümör gruplarına göre ONUÇ (p=0.04) daha yüksek saptanmştır. Derece 3 IDK olgularında, derece 1 IDK olgularına göre ONKÇ (p=0.04); İnvaziv Lobler Karsinom olgularına göre de ONA (p<0.01), ONÇ (p=0.02), ONUÇ (p=0.01) ve ONKÇ (p=0.02) daha yüksek saptanmıştır. Tümör nekrozuna sahip olgularda, tümör nekrozu olmayan olgulara göre ONA (P=0.01), ONÇ (p<0.01), ONUÇ (P=0.01) ve ONKÇ (P<0.01) daha yüksek saptanmıştır. Immünohistokimyasal olarak, Cerb-B2 pozitif meme karsinomlu olgular, Cerb-B2 negatif olgulara göre ONA (P<0.01), ONÇ (p=0.01), ONUÇ (P<0.01) ve ONKÇ (P=0.01) daha yüksek saptanmıştır.

Sonuç: Özellikle nükleus alanına dayalı nükleer morfometrik değerlendirme; tümör derecesi, histolojik subtip ve tümör nekrozu yanısıra Cerb-B2 ekspresyon profili ile ilişkili olduğundan prognostik değerlendirmede yol gösterici olabilir.

Anahtar Kelimeler

görüntü sitometrisi, immünohistokimya, karsinom, meme, prognoz

Relation of Nuclear Morphometry with Clinicopathologic Prognostic Parameters and Immunohistochemical ER, PR and Cerb-B2 Expressions in Breast Carcinoma

Öz

Purpose: Computerized histomorphometric analyses have been widely used as a diagnostic tool for the differential diagnosis of various tumors including breast carcinoma, as well as the grading of malignant tumors and evaluation of prognosis and therapeutic response. The aim of the present study is to determine the association between nuclear morphometric variables and clinicopathologic prognostic parameters including ER, PR, and Cerb-B2 expressions in breast carcinoma.

Materials and Methods: A hundred and five patients with breast carcinoma were evaluated in terms of various nuclear morphometric parameters, including mean nuclear area (MNA), mean nuclear perimeter (MNP), mean nuclear long diameter (MNLD), and mean nuclear short diameter (MNSD). Fifty tumor cell nuclei, per lesion, on Hematoxylen eosin-stained slides were measured using a digital image analysis system. The relation between calculated data and clinicopathologic prognostic parameters were assessed with statistical methods.

Results: Among histologic subtypes, invasive ductal carcinoma (IDC) had higher MNLD than other tumors group (p=0.04). Grade III IDC had higher MNA (p=0.04) and MNSD (p=0.02) than grade I IDC and higher MNA (p=0.01), MNP (p=0.02), MNLD (p=0.01), and MNSD (p=0.02) than invasive lobular carcinoma. MNA (p=0.01), MNP (p=0.009), MNLD (p=0.01), and MNSD (p=0.006) were higher in tumors having necrosis than tumors without necrosis. Immunohistochemically, Cerb-B2 positive tumors exhibited higher MNA (p=0.001), MNP (p=0.001), MNLD (p=0.001) and MNSD (p=0.001) than Cerb-B2 negative tumors.

Conclusion: Nuclear morphometric assessment, especially using MNA, is a valuable tool due to its significant association with clinicopathologic prognostic parameters including tumor grade, histologic subtype, tumor necrosis and Cerb-b2 expression profile.

Anahtar Kelimeler

breast, carcinoma, image cytometry, immunohistochemistry, prognosis

Kaynakça

• 1. Ullah MF. Breast Cancer: Current Perspectives on the Disease Status. Ahmed A ed. Breast Cancer Metastasis and Drug Resistance. Springer;2019:51-64.
• 2. Kontzoglou K, Palla V, Karaolanis G, et al. Correlation between Ki67 and breast cancer prognosis. Oncology. 2013;84(4):219-225.
• 3. Abdalla F, Boder J, Markus R, Hashmi H, Buhmeida A, Collan Y. Correlation of nuclear morphometry of breast cancer in histological sections with clinicopathological features and prognosis. Anticancer Res. 2009;29(5):1771-1776.
• 4. Buhmeida A, Al-Maghrabi J, Merdad A, et al. Nuclear morphometry in prognostication of breast cancer in Saudi Arabian patients: comparison with European and African breast cancer. Anticancer Res. 2010;30(6):2185-2191.
• 5. Kashyap A, Jain M, Shukla S, Andley M. Study of nuclear morphometry on cytology specimens of benign and malignant breast lesions: A study of 122 cases. J Cytol. 2017;34(1):10-15.
• 6. Kronqvist P, Kuopio T, Collan Y. Breast cancer prognostication: Morphometric thresholds for nuclear grading. Br J Cancer. 1998;78:800-805.
• 7. Sheela Devi CS, Suchitha S, Veerendrasagar RS. Evaluation of Nuclear Morphometry and Ki-67 Index in Clear Cell Renal Cell Carcinomas: a Five-Year Study. Iran J Pathol. 2017;12(2):150-157.
• 8. Ikeguchi M, Oka S, Saito H, et al. Computerized nuclear morphometry: a new morphologic assessment for advanced gastric adenocarcinoma. Ann Surg. 1999;229(1):55-61.
• 9. Veltri RW, Christudass CS, Isharwal S. Nuclear morphometry, nucleomics and prostate cancer progression. Asian J Androl. 2012;14(3):375-384.
• 10. Razavi MA, Wong J, Akkera M, et al. Nuclear morphometry in indeterminate thyroid nodules. Gland Surg. 2020;9(2):238-244.
• 11. Sobin LH, Gospodarowicz MK, Wittekind Ch. International Union Against Cancer (UICC) TNM Classification of Malignant Tumors. 7th ed. Oxford, UK: Wiley-Blackwell;2009.
• 12. Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res. 2009;7(1-2):4-13.
• 13. Yin L, Duan JJ, Bian XW, Yu SC. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res. 2020;22(1):61.
• 14. Ikpatt OF, Kuopio T, Collan Y. Nuclear morphometry in African breast cancer. Image Anal. Stereol. 2002;21(2):145-150.
• 15. Chiusa L, Margaria E, Pich A. Nuclear morphometry in male breast carcinoma: association with cell proliferative activity, oncogene expression, DNA content and prognosis. Int J Cancer. 2000;89(6):494-499.
• 16. Ladekarl M, Sørensen FB. Quantitative histopathological variables in in situ and invasive ductal and lobular carcinomas of the breast. APMIS. 1993;101(7-12):895-903.
• 17. Tan PH, Goh BB, Chiang G, Bay BH. Correlation of nuclear morphometry with pathologic parameters in ductal carcinoma in situ of the breast. Mod Pathol. 2001;14(10):937-941.
• 18. Prvulović I, Kardum-Skelin I, Sustercić D, Jakić-Razumović J, Manojlović S. Morphometry of tumor cells in different grades and types of breast cancer. Coll Antropol. 2010;34(1):99-103.
• 19. Selvarajan S, Wong KY, Khoo KS, Bay BH, Tan PH. Over-expression of c-erbB-2 correlates with nuclear morphometry and prognosis in breast carcinoma in Asian women. Pathology. 2006;38(6):528-533.
• 20. Rosen PP. Rosen's breast pathology. 4th ed. Philadelphia, Pa, USA:Lippincott Williams & Wilkins;2014.
• 21. Poller DN, Galea M, Pearson D, et al. Nuclear and flow cytometric characteristics associated with overexpression of the c-erbB-2 oncoprotein in breast carcinoma. Breast Cancer Res Treat. 1991;20(1):3-10.