Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
Clinical Significance of Ki-67 Proliferation Index and p53 Gene Expression in the Evaluation of Hormone Profiles, Invasiveness and Pre- and Post-operative Assessment of Pituitary Macroadenomas
Ki-67 Proliferasyon İndeksi ve p53 Gen Ekspresyonunun Hipofiz Makroadenomalarının Hormon Profilleri, İnvazyon Dereceleri ve Operasyon Öncesi ve Sonrası Değerlendirilmesindeki Klinik Önemi
Ahmet Mesrur HALEFOĞLUa, Canan TANIKb, Mustafa KARABİNAa
aDepartment of Radiology, University of Health Sciences Şişli Hamidiye Etfal Training and Research Hospital, İstanbul, TURKEY
bDepartment of Pathology, University of Health Sciences Şişli Hamidiye Etfal Training and Research Hospital, İstanbul, TURKEY
Turkiye Klinikleri J Med Sci. 2021;41(1):22-35
doi: 10.5336/medsci.2020-79897
Article Language: EN
Full Text
ABSTRACT
Objective: The aim of this study was to investigate the clinical significance of Ki-67 proliferation index and p53 gene expression in the pre-operative and post-operative evaluation of pituitary macroadenomas. Material and Methods: We retrospectively evaluated 81 pituitary macroadenoma patients, where pre-operative, six-month and one-year follow-up post-operative dynamic contrastenhanced magnetic resonance imaging examinations were present in our picture archiving and data system. All patients underwent surgical tumor removal and were pathologically diagnosed as having macroadenomas. Results: In Ki-67 positive macroadenoma cases, maximal tumor diameter was found significantly higher than in Ki-67 negative adenoma cases. When tumor invasiveness was compared based on Hardy's classification with the Ki-67 proliferation index values of macroadenomas, no statistically significant correlation was found between tumor invasiveness and Ki-67 values. We can state that there is a strong correlation between Ki-67 positiveness and increase in residual tumor dimensions. In p53 negative and positive macroadenoma cases, there was no significant correlation between p53 gene expression and maximal tumor diameter. When we compared the tumor invasiveness was compared based on Hardy's classification with the p53 gene expression of macroadenomas, no statistically significant correlation was found between tumor invasiveness and p53 values. We can say that there is a strong correlation between p53 gene expression positiveness and increase in residual tumor dimensions. Conclusion: Ki-67 proliferation index and p53 gene expression level determination of macroadenomas and their association with the hormone profiles, invasiveness, preoperative primary tumor and post-operative residual tumor dimension parameters can be combined in order to predict early tumor progression and patient prognosis.

Keywords: Immunohistochemistry; magnetic resonance imaging; pituitary adenoma; recurrence
ÖZET
Amaç: Hipofiz makroadenomlarının, operasyon öncesi ve sonrası değerlendirilmesinde Ki-67 proliferasyon indeksi ve p53 gen ekspresyonunun klinik önemini araştırmak. Gereç ve Yöntemler: Çalışmamızda, operasyon öncesi ve sonrası 6. ay ve 1. yıl takip dinamik kontrastlı manyetik rezonans görüntüleme incelemeleri resim arşiv ve data sistemi içerisinde bulunan 81 hipofiz makroadenoma hastasını retrospektif olarak değerlendirdik. Tüm hastalarda, cerrahi olarak tümör çıkarıldı ve patolojik olarak makroadenoma tanısı konuldu. Bulgular: Ki-67 pozitif olan makroadenoma olgularında maksimal tümör boyutları, Ki-67 negatif olan adenoma olgularına göre belirgin derecede yüksek bulundu. Hardy'nin klasifikasyonuna göre tümör invazyonu ile makroadenomaların Ki-67 proliferasyon indeks değerleri karşılaştırıldığında, tümör invazyonu ile Ki-67 proliferasyon indeks değerleri arasında istatistiksel olarak anlamlı bir korelasyon saptanmadı. Ki-67 pozitifliği ile rezidüel tümör boyutlarındaki artış arasında güçlü bir korelasyon bulunduğunu söyleyebiliriz. Rezidüel tümör boyut artışı ile Hardy'nin klasifikasyonu arasında istatistiksel olarak önemli bir korelasyon mevcut değildir. p53 negatif ve pozitif makroadenoma olgularında, p53 gen ekspresyonu ile maksimal tümör boyutu arasında önemli bir korelasyon bulunmadı. Makroadenomaların, p53 gen ekspresyonu ile Hardy'nin klasifikasyonuna göre tümör invazyonu karşılaştırıldığında, p53 değerleri ile tümör invazyonu arasında istatistiksel olarak önemli bir korelasyon saptanmadı. Operasyon sonrası rezidüel tümör değerlendirilmesinde, p53 gen ekspresyon pozitifliği ile rezidüel tümör boyutları artışı arasında kuvvetli bir korelasyon bulunduğunu söyleyebiliriz. Sonuç: Makroadenomaların Ki-67 proliferasyon indeksi ve p53 gen ekspresyon düzeylerinin saptanması ve bunların hormon profilleri, invazyon, operasyon öncesi primer tümör ve operasyon sonrası rezidüel tümör boyutu parametleri ile olan ilişkileri erken tümör progresyonunun ve hasta prognozunun tahmininde kombine olarak kullanılabilir.

Anahtar Kelimeler: İmmünohistokimyasal; manyetik rezonans görüntüleme; hipofizer adenoma; nüks
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