Prostat kanseri olgularında KRAS, BRAF ve pık3ca mutasyon analizi ve klinikopatolojik parametrelerle ilişkisi
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Dosyalar
Tarih
2020
Yazarlar
Dergi Başlığı
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Cilt Başlığı
Yayıncı
Düzce Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Prostat kanseri (PKa), dünyada erkeklerde en sık görülen kanserlerdendir ve kanser mortalitesinde beşinci sıradadır. KRAS, BRAF vb. hedeflerin mutasyonlarıyla RAS/RAF/MAPK yolu aktivasyonunun, çeşitli malignitelere neden olduğu bilinmektedir. Ayrıca fosfotidilinozitol-3-kinaz (PI3K) sinyal yolağı, kanserde regülasyonu sık bozulan yollardan biridir. Çalışmamızda; bölümümüzde tanı alan 24 prostatik asiner adenokarsinom olgusunda BRAF, KRAS, PIK3CA genlerindeki mutasyon oranlarını ve klinikopatolojik özelliklerle ilişkilerini araştırdık. Gereç ve Yöntem: Bu çalışmaya Düzce Üniversitesi Tıp Fakültesi Patoloji ABD'de 2012-2018 yılları arasında PKa tanısı alan 24 ardışık prostatektomi olgusu dâhil edilmiştir. Olgular Gleason skoru düşük ve yüksek olarak iki gruba ayrılmıştır. Tüm olguların prostatektomi materyallerine ait formalin fikse parafine gömülü (FFPG) bloklarından mikroarray hibridizasyon yöntemi ile mutasyon analizi yapılmıştır. Mutasyon sıklıkları, hastaların demografik, histopatolojik ve klinik bulgularıyla karşılaştırılmıştır. Bulgular: Olguların 3/24 (%12.5)'ünde KRAS mutasyonu (G12S, G12D-G12S, Q12R) saptanmış olup, hiçbirinde BRAF ve PIK3CA mutasyonları gözlenmemiştir. Gruplar arasında KRAS mutasyon sıklığı açısından anlamlı fark bulunmamıştır. KRAS mutasyon pozitifliği ile yaş (p=0.240), preop PSA (p=0.085), Gleason skoru (p=0.075), pT (p=0.250), AJCC evre (p=0.050), lenf nodu metastazı (p=0.999), uzak metastaz (p=0.999), vasküler invazyon (p=0.999), perinöral invazyon (p=0.550), periprostatik yayılım (p=0.530), seminal vezikül invazyonu (p=0.546), cerrahi sınır pozitifliği (p=0.550), biyokimyasal rekürrens (p=0.999) ve aile öyküsü (p=0.209) arasında anlamlı ilişki saptanmamıştır. Tartışma: Çalışmamızda KRAS mutasyon sıklığı oranlarımız (%12.5), Asya popülasyonlarında yapılan çalışmalar ile benzerdir (Kore: %7.3, Çin: %9.1, İran: %5.7). Türkiye'de yapılan farklı iki çalışmada PKa'da KRAS mutasyon sıklığı %8.8 ve %40 oranında bildirilmiştir. Literatürde BRAF ve PIK3CA mutasyon sıklıkları, çalışmamızla (%0) uyumlu olarak sırasıyla %0-15 ve %0-10,4 aralığında bildirilmiştir. Sonuç: Bu çalışma Türkiye'de PKa'da BRAF ve PIK3CA mutasyon analizinin yapıldığı ilk, KRAS mutasyon analizinin yapıldığı üçüncü çalışmadır. Söz konusu mutasyonların PKa'daki rolünü daha net belirlemek ve tedavi yaklaşımları geliştirmek için ileri evre olguların ağırlıkta olduğu geniş serilerde çalışmalara ihtiyaç vardır.
Aim: Prostate cancer (PCa) is one of the most common cancers in men in the world and the fifth cause of cancer-related deaths. It is known that activation of the RAS/RAF/MAPK pathway causes various malignancies by mutations such as KRAS, BRAF, etc. In addition, the phosphatidylinositol-3-kinase (PI3K) signaling pathway is one of the commonly deregulated pathways in cancer. In our study; we aimed to investigate the mutation rates of BRAF, KRAS, PIK3CA genes in 24 prostatic acinar adenocarcinoma cases diagnosed in our department and evaluate the mutation status' correlation with the clinicopathological characteristics of the patients. Material and Method: In this study, 24 consecutive prostatectomy cases diagnosed with PCa in Düzce University Faculty of Medicine, Department of Pathology between 2012-2018 were included. The cases were divided into two groups based on low and high Gleason scores. Mutation analysis was performed by microarray hybridization method from formalin-fixed paraffin-embedded (FFPG) blocks of prostatectomy materials of all cases. Mutation frequencies were compared with the demographic, histopathological, and clinical findings of the patients. Results: KRAS mutation (G12S, G12D-G12S, Q12R) was detected in 3/24 (12.5%) of the cases, and BRAF and PIK3CA mutations were not observed in any of them. There was no significant difference between the groups in terms of KRAS mutation frequency. There was no significant correlation between KRAS mutation vs age (p = 0.240), preop PSA (p = 0.085), Gleason score (p = 0.075), pT (p = 0.250), AJCC stage (p = 0.050), lymph node metastasis (p = 0.999), distant metastasis (p = 0.999), vascular invasion (p = 0.999), perineural invasion (p = 0.550), periprostatic spread (p = 0.530), seminal vesicle invasion (p = 0.546), surgical margin positivity (p = 0.550), biochemical recurrence (p = 0.999) and family history (p = 0.209). Discussion: The KRAS mutation frequency rate (12.5%) in our study is similar to those in Asian populations (Korea: 7.3%, China: 9.1, Iran: 5.7). In Turkey, two different studies have reported 8.8% and 40% frequency of KRAS mutation in PCa. In the literature, BRAF and PIK3CA mutation frequencies have been reported in the range of 0-15% and 0-10.4%, respectively, consistent with our study (0%). Conclusion: This study is the first report analyzing BRAF and PIK3CA mutations while the third report indicating KRAS mutation in PCa from Turkey. In order to more clearly determine the role of these mutations in PCa and to develop treatment approaches, studies are needed in large series with patient of predominantly advanced stage.
Aim: Prostate cancer (PCa) is one of the most common cancers in men in the world and the fifth cause of cancer-related deaths. It is known that activation of the RAS/RAF/MAPK pathway causes various malignancies by mutations such as KRAS, BRAF, etc. In addition, the phosphatidylinositol-3-kinase (PI3K) signaling pathway is one of the commonly deregulated pathways in cancer. In our study; we aimed to investigate the mutation rates of BRAF, KRAS, PIK3CA genes in 24 prostatic acinar adenocarcinoma cases diagnosed in our department and evaluate the mutation status' correlation with the clinicopathological characteristics of the patients. Material and Method: In this study, 24 consecutive prostatectomy cases diagnosed with PCa in Düzce University Faculty of Medicine, Department of Pathology between 2012-2018 were included. The cases were divided into two groups based on low and high Gleason scores. Mutation analysis was performed by microarray hybridization method from formalin-fixed paraffin-embedded (FFPG) blocks of prostatectomy materials of all cases. Mutation frequencies were compared with the demographic, histopathological, and clinical findings of the patients. Results: KRAS mutation (G12S, G12D-G12S, Q12R) was detected in 3/24 (12.5%) of the cases, and BRAF and PIK3CA mutations were not observed in any of them. There was no significant difference between the groups in terms of KRAS mutation frequency. There was no significant correlation between KRAS mutation vs age (p = 0.240), preop PSA (p = 0.085), Gleason score (p = 0.075), pT (p = 0.250), AJCC stage (p = 0.050), lymph node metastasis (p = 0.999), distant metastasis (p = 0.999), vascular invasion (p = 0.999), perineural invasion (p = 0.550), periprostatic spread (p = 0.530), seminal vesicle invasion (p = 0.546), surgical margin positivity (p = 0.550), biochemical recurrence (p = 0.999) and family history (p = 0.209). Discussion: The KRAS mutation frequency rate (12.5%) in our study is similar to those in Asian populations (Korea: 7.3%, China: 9.1, Iran: 5.7). In Turkey, two different studies have reported 8.8% and 40% frequency of KRAS mutation in PCa. In the literature, BRAF and PIK3CA mutation frequencies have been reported in the range of 0-15% and 0-10.4%, respectively, consistent with our study (0%). Conclusion: This study is the first report analyzing BRAF and PIK3CA mutations while the third report indicating KRAS mutation in PCa from Turkey. In order to more clearly determine the role of these mutations in PCa and to develop treatment approaches, studies are needed in large series with patient of predominantly advanced stage.
Açıklama
YÖK Tez No: 654485
Anahtar Kelimeler
Patoloji, Pathology
