Fıgo grade 1 endometrioid tip endometrial karsinomlarda immünhistokimyasal pole, mismatch repair(MMR) ve p53 mutasyonlarının myometrial invazyon ile ilişkisi
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Tarih
2023
Yazarlar
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Yayıncı
Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Endometrial Karsinomlar (EK) en sık görülen jinekolojik tümörlerden biridir. The International Agency for Research on Cancer (IARC)' ın bir parçası olan The Global Cancer Observatory (GCO)’ nin GLOBOCAN 2020 veri tabanına göre EK 417.000 yeni vaka ve 97.000 ölümle kadınlarda en sık teşhis edilen altıncı kanserdir ve kadın tümörlerinin %4,5’ ini oluşturmaktadır. İnsidans oranlarının son yirmi yılda düştüğü diğer birçok kanser türünün aksine, endometriyum kanserinin küresel insidansı artmaya devam etmektedir. EK’nin ilk alt tip sınıflandırması, 1983' te Bokhman tarafından, klinik ve hormonal özelliklere dayalı olarak Tip I ve Tip II EK olarak yapılmıştır. 2013 yılında, EK’ lerin Kanser Genom Atlası (TCGA) tarafından entegre bir moleküler karakterizasyonu, mutasyon yükü ve somatik kopya sayısı varyasyonlarına dayalı olarak dört gruba bölünebileceğini gösterilmiştir. Bu 4 alt grup; POLE Ultra mutasyonu, Mismatch repair eksikliği (MMRd), P53 mutasyonu (p53abn) ve Spesifik moleküler profili olmayan karsinomlar (p53 wild type-p53wt) olarak belirlenmiştir. Çalışmamızda Meram Tıp Fakültesi Tıbbi Patoloji Anabilim Dalında grade 1 endometrioid tip EK tanısı almış olgular yeniden değerlendirildi. Olgulara immünhistokimyasal olarak POLE, P53, MMR(MLH-1,MSH-2,MSH-6,PMS-2) boyaları uygulandı. Elde edilen veriler klinikopatolojik parametrelerle istatiksel olarak karşılaştırıldı. Çalışmamızda olguların hiçbirinde immünhistokimyasal olarak POLE ekspresyonu görülmedi. P53 final skor sonuçları ile MMRp/MMRd grupları arasında istatiksel olarak anlamlı fark saptanmıştır (p=0,005). P53 final skoru negatif olan 21 olguda, MMR proteinlerinden herhangi birinde ekspresyon kaybı izlenmedi. Çalışmamızdaki 50 olgunun %40’ ı (n=20) MMRd grubunda, %60’ ı MMRp (N=30) grubunda saptanmıştır.
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MMRd grubunda olan 20 adet olgunun %75’ inde (n=15) MLH-1 ve PMS-2 ile ekspresyon kaybı, %15’inde (n=3) MSH-2 ve MSH-6 ile ekspresyon kaybı, %5’ inde (n=1) ise sadece PMS-2 ve sadece MSH-6 ile ekspresyon kaybı izlenmiştir. Klinik ve histopatolojik parametlerden yaş ile myometrial invazyon arasında pozitif yönde düşük korelasyon izlendi (r=0,373, p=0,008). Lenf nodu metastazı ile adneksiyel tutulum arasında orta derecede korelasyon izlendi (r=0,484, p=0,00). Evre ile myometrial invazyon arasında pozitif yönde kuvvetli korelasyon izlendi (r=0,818, p=0,00). Evre ve alt uterin segment tutulumu ile pozitif yönde orta derecede, serviks tutulumu ile arasında pozitif yönde iyi derecede korelasyon izlendi (r değerleri sırasıyla; r=0,520 r=0,664; p değerleri sırasıyla p=0,00 p=0,00). EK’lerin immunhistokimyasal POLE, p53 ve MMR ekspresyonuna göre alt tiplendirme yapılmasının cerrahinin adjuvan tedavilerin ve hedefe yönelik tedavilerin planlanması açısından önemli olduğunu düşünmektekteyiz.
ndometrial cancer (EC) is one of the most common gynecological tumors. According to the GLOBOCAN 2020 database of the Global Cancer Observatory (GCO), part of the International Agency for Research on Cancer (IARC), endometrial cancer is the sixth most commonly diagnosed cancer in women, accounting for 417.000 new cases and 97.000 deaths, or 4.5% of all tumors in women. The global incidence of endometrial cancer continues to rise, unlike many other cancers where incidence rates have declined over the past two decades. The first subtype classification of endometrial cancer was made by Bokhman in 1983 as Type I and Type II endometrial cancer based on clinical and hormonal characteristics. In 2013, The Cancer Genome Atlas (TCGA) showed that EC’s can be divided into four groups based on integrated molecular characterization, mutational burden and somatic copy number variations. These 4 subgroups are POLE ultra mutation, mismatch repair deficiency (MMRd), P53 mutation (p53abn) and carcinoma without specific molecular profile (p53 wild type-p53wt). In our study, cases diagnosed as grade 1 endometrioid type endometrial carcinoma at the Department of Medical Pathology, Meram Faculty of Medicine were re-evaluated. POLE, P53, MMR (MLH-1, MSH-2, MSH-6, PMS-2) staining was performed by immunohistochemistry. Data were statistically compared with clinicopathologic parameters. There was a statistically significant difference between p53 final score results and MMRp/MMRd groups (p=0.005). In 21 cases with negative p53 final score, no loss of expression of any of the MMR proteins was observed. Of the 50 cases in our study, 40% (n=20) were in the MMRd group and 60% in the MMRp group (n=30). Among the 20 cases in the MMRd group, 75% (n=15) had loss of MLH-1 and PMS-2 expression, 15% (n=3) had loss of MSH-2 and MSH-6 expression, and 5% (n=1) had loss of PMS-2 and MSH-6 expression only. Among clinical and histopathologic parameters, there was a low positive correlation between age and myometrial invasion (r=0.373, p=0.008). There was a moderate positive correlation between lymph node metastasis and adnexal involvement (r=0.484, p=0.00), a strong positive correlation between stage and myometrial invasion (r=0.818, p=0.00), a moderate positive correlation with stage and lower uterine segment involvement, and a significant positive correlation with cervical involvement (r vii values r=0.520 r=0.664; p values p=0.00 p=0.00, respectively). We believe that subtyping of endometrial cancer according to immunohistochemical POLE, p53 and MMR expression is important for planning surgical, adjuvant and targeted therapies.
ndometrial cancer (EC) is one of the most common gynecological tumors. According to the GLOBOCAN 2020 database of the Global Cancer Observatory (GCO), part of the International Agency for Research on Cancer (IARC), endometrial cancer is the sixth most commonly diagnosed cancer in women, accounting for 417.000 new cases and 97.000 deaths, or 4.5% of all tumors in women. The global incidence of endometrial cancer continues to rise, unlike many other cancers where incidence rates have declined over the past two decades. The first subtype classification of endometrial cancer was made by Bokhman in 1983 as Type I and Type II endometrial cancer based on clinical and hormonal characteristics. In 2013, The Cancer Genome Atlas (TCGA) showed that EC’s can be divided into four groups based on integrated molecular characterization, mutational burden and somatic copy number variations. These 4 subgroups are POLE ultra mutation, mismatch repair deficiency (MMRd), P53 mutation (p53abn) and carcinoma without specific molecular profile (p53 wild type-p53wt). In our study, cases diagnosed as grade 1 endometrioid type endometrial carcinoma at the Department of Medical Pathology, Meram Faculty of Medicine were re-evaluated. POLE, P53, MMR (MLH-1, MSH-2, MSH-6, PMS-2) staining was performed by immunohistochemistry. Data were statistically compared with clinicopathologic parameters. There was a statistically significant difference between p53 final score results and MMRp/MMRd groups (p=0.005). In 21 cases with negative p53 final score, no loss of expression of any of the MMR proteins was observed. Of the 50 cases in our study, 40% (n=20) were in the MMRd group and 60% in the MMRp group (n=30). Among the 20 cases in the MMRd group, 75% (n=15) had loss of MLH-1 and PMS-2 expression, 15% (n=3) had loss of MSH-2 and MSH-6 expression, and 5% (n=1) had loss of PMS-2 and MSH-6 expression only. Among clinical and histopathologic parameters, there was a low positive correlation between age and myometrial invasion (r=0.373, p=0.008). There was a moderate positive correlation between lymph node metastasis and adnexal involvement (r=0.484, p=0.00), a strong positive correlation between stage and myometrial invasion (r=0.818, p=0.00), a moderate positive correlation with stage and lower uterine segment involvement, and a significant positive correlation with cervical involvement (r vii values r=0.520 r=0.664; p values p=0.00 p=0.00, respectively). We believe that subtyping of endometrial cancer according to immunohistochemical POLE, p53 and MMR expression is important for planning surgical, adjuvant and targeted therapies.
Açıklama
Anahtar Kelimeler
Endometrial kanser, Mismatch Repair (MMR), P53, POLE, Endometrial cancer, Mismatch Repair (MMR), P53, POLE
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WoS Q Değeri
Scopus Q Değeri
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Künye
Tekecik, T. Z. (2023). Fıgo grade 1 endometrioid tip endometrial karsinomlarda immünhistokimyasal pole, mismatch repair(MMR) ve p53 mutasyonlarının myometrial invazyon ile ilişkisi. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi Cerrahi Tıp Bilimleri Bölümü Tıbbi Patoloji Anabilim Dalı, Konya.
