Mide karsinomlarında, mikrosatellit instabilitesi (MSI), HER2 ve PD-L1 ekspresyonunun klinikopatolojik ve prognostik önemi
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Dosyalar
Tarih
2021
Yazarlar
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Yayıncı
Selçuk Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Mide kanseri dünya çapında en sık görülen beşinci kanserdir ve kansere bağlı ölümlerin önemli nedenlerinden biridir. Mikrosatellit instabilitesi (MSI), mide kanserinde moleküler sınıflamada alt tiplerden biridir ve kısa tekrarlanan DNA dizilerinde (mikrosatellitler) uzunlukta değişiklikle karakterizedir. HER2 tümör hücresi proliferasyonu, apoptozisi, adezyonu, migrasyonu ve diferansiasyonu ile ilişkili reseptör ailesinin bir üyesidir. Programlanmış ölüm ligandı 1 (PD-L1), PD-1 (Programlanmış ölüm-1) reseptörüne bağlanarak immün hücre toleransının korunmasında rol alır. Çalışmamızda mide karsinomu olgularında MSI oranı %8,5 olarak belirlenmiştir. Bu hastaların yaş ortalaması, MSS hastalardan anlamlı olarak yüksek bulunmuştur (p=0,020). Lenf nodu metastazı olan MSI olgularında ekstrakapsüler yayılım görülmemiştir (p=0,020). HER2 ekspresyon durumu ile MMR durumu, PD-L1 ekspresyonu ve diğer klinikopatolojik özellikler arasında istatistiksel olarak anlamlı bir ilişki görülmemiştir (p>0,05). PD-L1'in immünopozitif ekspresyon oranı %70,8'dir. Bu olguların %89,3'ünde yalnızca immün hücreler, %10,7'sinde hem tümör hem de immün hücreler immünopozitiftir. Sadece tümör hücrelerinde, PD-L1 ekspresyonu durumu 65 yaş ve üzerinde anlamlı şekilde daha yüksektir (p=0,025) ve lenf nodu metastazı olanlarda ekstrakapsüler yayılım görülmemiştir (p=0,048). Tümör hücrelerinde PD-L1 ekspresyonu izlenen hastalarda MSI oranı anlamlı olarak daha yüksektir (p<0,001). 65 ve üzeri yaş (p<0,001), cerrrahi sınırda tümör varlığı (p=0,006), pTNM evre 3 ve 4 (p=0,001), metastatik lenf nodu sayısının artışının (p<0,001) ölüm riskini artırdığı ve genel sağkalımı olumsuz etkilediği görülmüştür. pTNM evre 3 ve 4 (p=0,042), uzak metastaz varlığı (p=0,033), lenfovasküler invazyon varlığının progresyon riskini artırdığı görülmüştür (p=0,034). MSI, HER2 ve PD-L1'e dair literatürde çok sayıda çalışma mevcut olmakla birlikte prognostik önemi hala tartışmalıdır. Daha kapsamlı çalışmalar ile bu belirteçlerin rollerinin daha iyi anlaşılması mide kanserine bağlı ölümlerin azaltılmasında önemlidir.
Gastric cancer is the fifth most common cancer worldwide and one of the major causes of cancer-related deaths. Microsatellite instability (MSI) is one of the subtypes in the molecular classification of gastric cancer and is characterized by variation in length in short repetitive DNA sequences (microsatellites). HER2 is a member of the receptor family associated with tumor cell proliferation, apoptosis, adhesion, migration and differentiation. Programmed death ligand 1 (PD-L1) plays a role in maintaining immune cell tolerance by binding to the PD-1 (Programmed death-1) receptor. In our study, the rate of MSI in gastric carcinoma cases was determined as 8,5%. The mean age of these patients was found to be significantly higher than the MSS patients (p=0,020). Extracapsular spread was not observed in MSI cases with lymph node metastasis (p=0,020). There was no statistically significant correlation between HER2 expression status and MMR status, PD-L1 expression and other clinicopathological features (p>0,05). The immunopositive expression rate of PD-L1 is 70,8%. In 89,3% of these cases, only immune cells are immunopositive, and in 10,7%, both tumor and immune cells are immunopositive. Only in tumor cells, PD-L1 expression status was significantly higher at 65 years and older (p=0,025), and extracapsular spread was not seen in those with lymph node metastases (p=0,048). The rate of MSI was significantly higher in patients with PD-L1 expression in tumor cells (p<0,001). Age 65 and over (p<0,001), presence of tumor at the surgical margin (p=0,006), pTNM stages 3 and 4 (p=0,001), increased number of metastatic lymph nodes (p<0,001) increased the risk of death and adversely affected overall survival. It was observed that pTNM stages 3 and 4 (p=0,042), presence of distant metastases (p=0,033), presence of lymphovascular invasion increased the risk of progression (p=0,034). Although there are many studies in the literature on MSI, HER2 and PD-L1, its prognostic significance is still controversial. A better understanding of the roles of these markers with more comprehensive studies is important in reducing deaths from gastric cancer.
Gastric cancer is the fifth most common cancer worldwide and one of the major causes of cancer-related deaths. Microsatellite instability (MSI) is one of the subtypes in the molecular classification of gastric cancer and is characterized by variation in length in short repetitive DNA sequences (microsatellites). HER2 is a member of the receptor family associated with tumor cell proliferation, apoptosis, adhesion, migration and differentiation. Programmed death ligand 1 (PD-L1) plays a role in maintaining immune cell tolerance by binding to the PD-1 (Programmed death-1) receptor. In our study, the rate of MSI in gastric carcinoma cases was determined as 8,5%. The mean age of these patients was found to be significantly higher than the MSS patients (p=0,020). Extracapsular spread was not observed in MSI cases with lymph node metastasis (p=0,020). There was no statistically significant correlation between HER2 expression status and MMR status, PD-L1 expression and other clinicopathological features (p>0,05). The immunopositive expression rate of PD-L1 is 70,8%. In 89,3% of these cases, only immune cells are immunopositive, and in 10,7%, both tumor and immune cells are immunopositive. Only in tumor cells, PD-L1 expression status was significantly higher at 65 years and older (p=0,025), and extracapsular spread was not seen in those with lymph node metastases (p=0,048). The rate of MSI was significantly higher in patients with PD-L1 expression in tumor cells (p<0,001). Age 65 and over (p<0,001), presence of tumor at the surgical margin (p=0,006), pTNM stages 3 and 4 (p=0,001), increased number of metastatic lymph nodes (p<0,001) increased the risk of death and adversely affected overall survival. It was observed that pTNM stages 3 and 4 (p=0,042), presence of distant metastases (p=0,033), presence of lymphovascular invasion increased the risk of progression (p=0,034). Although there are many studies in the literature on MSI, HER2 and PD-L1, its prognostic significance is still controversial. A better understanding of the roles of these markers with more comprehensive studies is important in reducing deaths from gastric cancer.
Açıklama
Anahtar Kelimeler
Mide, Karsinom, MSI, HER2, PD-L1, Gastric, Carcinoma
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Mavi, Z. (2021). Mide karsinomlarında, mikrosatellit instabilitesi (MSI), HER2 ve PD-L1 ekspresyonunun klinikopatolojik ve prognostik önemi. (Uzmanlık Tezi). Selçuk Üniversitesi, Tıp Fakültesi, Konya.
