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Journals / Çukurova Anestezi ve Cerrahi Bilimler Dergisi / 2026 / Cilt: 9 Sayı: 3

Association of p16 Loss and EZH2 Overexpression with Clinicopathological Characteristics and Prognosis in Gastrointestinal Stromal Tumors

Gastrointestinal Stromal Tümörlerde p16 Ekspresyon Kaybı ve EZH2 Aşırı Ekspresyonunun Prognostik Önemi ve Klinikopatolojik Parametrelerle İlişkisi

Tuğba Toyran(ÇUKUROVA ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0001-9135-0265
Kivilcim Eren Ates(ÇUKUROVA ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0002-4951-8703
Tolga Köşeci(ÇUKUROVA ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0002-8696-0525
Uğur Topal(ÇUKUROVA ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0003-1305-2056
Cem Kaan Parsak(ÇUKUROVA ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0001-2345-6789
Yusuf Kemal Arslan(ÇUKUROVA ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0003-1308-8569
Arbil Açıkalın(ÇUKUROVA ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0001-6118-9853
Pages
870–884
Publication Date
2026-09-30
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⚡ TL;DR(Too Long; Didn't Read)

Expression of p16 and EZH2 was evaluated immunohistochemically and correlated with clinicopathological parameters and overall survival using Kaplan-Meier and Cox regression analyses.

📌 3 Key Takeaways

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Objective & Hypothesis:Abstract Aim: Gastrointestinal stromal tumors (GISTs) exhibit marked heterogeneous clinical behavior that is not fully captured by conventional risk classification systems.
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Key Findings & Data:This study aimed to evaluate the prognostic significance of loss of p16 expression and EZH2 overexpression and their relationship with clinicopathological parameters in GIST.
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Conclusion & Impact:Expression of p16 and EZH2 was evaluated immunohistochemically and correlated with clinicopathological parameters and overall survival using Kaplan-Meier and Cox regression analyses.
🔬Design:Araştırma Makalesi
📍Scope:2016 Verileri
⚙️Variables:EZH2 · Gastrointestinal stromal tümör · immünohistokimya

Abstract

Abstract Aim: Gastrointestinal stromal tumors (GISTs) exhibit marked heterogeneous clinical behavior that is not fully captured by conventional risk classification systems. This study aimed to evaluate the prognostic significance of loss of p16 expression and EZH2 overexpression and their relationship with clinicopathological parameters in GIST. Methods: In this retrospective study, 113 GIST cases diagnosed at a single institution between 2016 and 2026 were evaluated. Expression of p16 and EZH2 was evaluated immunohistochemically and correlated with clinicopathological parameters and overall survival using Kaplan-Meier and Cox regression analyses. Results: p16 loss was detected in 34 cases (30.1%) and EZH2 overexpression in 12 cases (10.6%). Both markers were significantly correlated with high mitotic activity, tumor necrosis, metastasis, multifocality, a high AFIP risk category, and elevated Ki-67 proliferation index (p<0.001 for all). Patients with EZH2 overexpression and those with p16 loss had significantly shorter overall survival in Kaplan–Meier analysis (log-rank p=0.001 and p<0.001, respectively). EZH2 overexpression was significantly more frequent in p16-loss cases (26.5% vs 3.8%, p=0.001). In multivariate analysis, loss of p16 expression (HR=2.159, p=0.040) and AFIP risk category (HR=1.661, p<0.001) remained independent prognostic factors, whereas EZH2 overexpression did not remain independent prognostic factor (HR=1.001, p=0.999). Conclusions: Loss of p16 expression is an independent adverse prognostic factor in GIST. Although EZH2 overexpression is associated with agressive clinicopathological features and shorter overall survival, its prognostic effect is not independent of established pathological risk factors. The significant association between EZH2 overexpression and p16 loss supports the potential involvement of the EZH2/PRC2-CDKN2A epigenetic pathway in GIST progression and warrants further molecular investigation. Keywords: EZH2; Gastrointestinal stromal tumor; Immunohistochemistry; p16; Prognosis

Özet

Özet Amaç: Gastrointestinal stromal tümörler (GİST), geleneksel risk sınıflandırma sistemleriyle tam olarak açıklanamayan belirgin klinik heterojenlik gösteren tümörlerdir. Bu çalışmada, GİST'lerde p16 ekspresyon kaybı ve EZH2 aşırı ekspresyonunun prognostik önemi ile bu belirteçlerin klinikopatolojik parametrelerle ilişkilerinin değerlendirilmesi amaçlandı. Yöntem: Bu retrospektif çalışmada, tek bir merkezde 2016–2026 yılları arasında tanı alan 113 GİST olgusu değerlendirildi. p16 ve EZH2 ekspresyonları immünohistokimyasal olarak değerlendirildi ve klinikopatolojik parametreler ile genel sağkalım arasındaki ilişkileri Kaplan–Meier ve Cox regresyon analizleri kullanılarak incelendi. Bulgular: p16 ekspresyon kaybı 34 (%30,1) olguda, EZH2 aşırı ekspresyonu ise 12 (%10,6) olguda saptandı. Her iki belirteç de yüksek mitotik aktivite, tümör nekrozu, metastaz, multifokalite, yüksek AFIP risk kategorisi ve yüksek Ki-67 proliferasyon indeksi ile anlamlı olarak ilişkili bulundu (tümü için p<0,001). Kaplan–Meier analizinde, EZH2 aşırı ekspresyonu gösteren ve p16 ekspresyon kaybı bulunan olgularda genel sağkalımın anlamlı olarak daha kısa olduğu belirlendi (sırasıyla log-rank p=0,001 ve p<0,001). EZH2 aşırı ekspresyonu, p16 ekspresyon kaybı bulunan olgularda,p16 ekspresyonuna sahip olgulara kıyasla anlamlı derecede daha sık izlendi (%26,5'e karşı %3,8; p=0,001). Çok değişkenli analizde, p16 ekspresyon kaybı (HR=2,159; p=0,040) ve AFIP risk kategorisi (HR=1,661; p<0,001) bağımsız prognostik faktörler olarak belirlenirken, EZH2 aşırı ekspresyonunun bağımsız prognostik önemini korumadığı görüldü (HR=1,001; p=0,999). Sonuç: p16 ekspresyon kaybı, GİST'lerde bağımsız bir olumsuz prognostik faktördür. EZH2 aşırı ekspresyonu agresif klinikopatolojik özellikler ve daha kısa genel sağkalım ile ilişkili olmakla birlikte, yerleşik patolojik risk faktörlerinden bağımsız prognostik değer göstermemektedir. EZH2 aşırı ekspresyonu ile p16 ekspresyon kaybı arasında saptanan anlamlı ilişki, EZH2/PRC2–CDKN2A epigenetik yolunun GİST progresyonundaki olası rolünü desteklemekte olup, bu ilişkinin moleküler düzeyde daha ileri çalışmalarla araştırılmasını gerekli kılmaktadır. Anahtar Kelimeler: EZH2; Gastrointestinal stromal tümör; İmmünohistokimya; p16; Prognoz.

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Cite This Article

Toyran, T., Ates, K. E., Köşeci, T., Topal, U., Parsak, C. K., Arslan, Y. K., Açıkalın, A. (2026). Association of p16 Loss and EZH2 Overexpression with Clinicopathological Characteristics and Prognosis in Gastrointestinal Stromal Tumors. Çukurova Anestezi ve Cerrahi Bilimler Dergisi, Cilt: 9 Sayı: 3, 870–884. https://doi.org/10.36516/jocass.1999690

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