HATALI EŞLEŞME GENLERİNDEN MLH1, PMS2, MSH6, MSH2’İN MİDE KANSERLERİNDE İMMÜNHİSTOKİMYASAL EKSPRESYONU; BİR DOKU MİKROARRAY ÇALIŞMASI

Amaç Mide kanserinde MLH1, PMS2, MSH6, MSH2’in immünhistokimyasal ekspresyonları ile klinikopatolojik parametrelerin arasındaki ilişkiyi değerlendirmeyi amaçladık. Gereç ve Yöntem Yüzüç primer mide adenokarsinom ve tümörsüz 27 mide mukozasına ait doku mikroarray (DMA) kesitlerine immünhistokimyasal uygulama yapıldı. Tüm markerlar nükleer boyanma açısından değerlendirildi. Markerlardan herhangi birinde negatiflik eksiklik olarak kabul edildi. Daha sonra hatalı eşleşme genlerinde eksiklik var (dMMR) ve hatalı eşleşme genleri sağlam (pMMR) olmak üzere 2 alt grup arasında karşılaştırma yapıldı. Bulgular Histopatolojik olarak intestinal ve intestinal olmayan alt tiplerinden, MSH2’nin intestinal grupta intestinal olmayan gruba göre ekspresyonunda anlamlı kayıp gözlendi. PMS2 ekspresyonu taşlı yüzük hücreli karsinomda diğer alt tiplere göre anlamlı olarak yüksekti. Ayrıca MLH1 ve PMS2 ekspresyonlarının kaybının orta/kötü diferansiye tümörlerde, iyi diferansiye tümörlere göre daha yüksek olduğunu gözlemledik. MLH1, MSH6, PMS2 ekspresyon kaybı ve dMMR olan olgularda pMMR’li olgulara göre perinöral invazyon anlamlı şekilde daha yüksekti. Kemoterapi/ radyoterapi alan ve almayan gruplar karşılaştırıldığında dMMR ve pMMR arasında anlamlı fark yoktu. MLH1, MSH2, MSH6, PMS2 ekspresyonları ile sağkalım arasında anlamlı ilişki bulunmadı. Sonuç Perinöral invazyon ile MLH1, MSH6 ve PMS2 ekspresyon kaybı arasında anlamlı ilişki bulduk. PMS2 ekspresyonu taşlı yüzük hücreli karsinomda diğer alt tiplere göre anlamlı olarak yüksekti.

Anahtar Kelimeler:

Mide adenokarsinom, MLH1, MSH2, PMS2, MSH6

THE IMMUNOHISTOCHEMICAL EXPRESSIONS OF MISMATCH REPAIR GENES MLH1, PMS2, MSH6, MSH2 IN GASTRIC CANCER; A TISSUE MICROARRAY STUDY

Objective We aimed to evaluate the correlation between the immunohistochemical expressions of MLH1, PMS2, MSH6, MSH2 and clinicopathological parameters in gastric carcinoma. Matherials and Methods Immunohistochemistry was performed on the tissue microarray (TMA) sections of 103 primary gastric adenocarcinoma and 27 gastric mucosal tissue samples without tumor. All markers were evaluated for the presence of nuclear staining. Negative expression in any of the markers was accepted as a deficiency. Then, the comparison was made between the two subgroups as; deficient mismatch repair (dMMR) and proficient mismatch repair (pMMR). Results The histopathological subtypes as intestinal and non-intestinal, the intestinal group showed significant deficient expression of MSH2 compared with the non-intestinal group. PMS2 expression was significantly higher in the other subtypes than signet ring cell carcinoma. Also, we observed that the loss of MLH1 and PMS2 expressions were higher in moderately/ poor differantiated tumors than the well differantiated ones. Perineural invasion was significantly higher in patients with loss of MLH1, MSH6, PMS2 expression and dMMR compared to patients with pMMR. There was no significant difference between dMMR and pMMR when compared the groups who received chemotherapy/ radiotherapy and who did not. There was not found significant relationship between MLH1, MSH2, MSH6, PMS2 expressions and survival. Conclusion We found a significant relationship between perineural invasion and the loss of expression of MLH1, MSH6 and PMS2. PMS2 expression was also significantly higher in the other subtypes of GC than signet ring cell carcinomas.

Keywords:

Gastric adenocarcinoma, MLH1, PMS2, MSH2, MSH6,

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