Kolorektal karsinomlarda KRAS, NRAS, BRAF, PIK3CA mutasyonlarının klinikopatolojik bulgularla ilişkisi
Küçük Resim Yok
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kolorektal karsinomlar, gastrointestinal sistemin en sık kanseridir ve kanser ilişkili, ölümlerin en önemli nedenlerindendir. Kolorektal kanserler, kadın ve erkeklerde tüm kanser türleri arasında üçüncü sırada görülmekte olup, çoğunluğu sporadiktir. Kolorektal karsinomların çoğunu adenokarsinomlar oluşturmaktadır. Çalışmamızda yeni nesil dizileme yöntemi ile kolorektal karsinomlarda, Kirsten Ras Onkogen Homolog Gen, V-Raf Murine Sarkom Viral Onkogen Homolog B1, Nöroblastom RAS Viral Onkogen Homolog, Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutasyonları ve klinikopatolojik parametreleri karşılaştırmak amacıyla 112 olgu çalışmaya alınmıştır. Olgulara ait Hematoksilen & Eozin boyalı lamlarda, tümör tomurcuğu, az diferansiye kümeler, tümör stroma oranı, inflamatuar hücre reaksiyonu, ekstra/intramural vasküler invazyon, perinöral invazyon, lenfovasküler invazyon, histolojik tümör alt tipi, histolojik tümör derecesi, primer tümör ve lenf nodu evresi, müsinöz komponent varlığı değerlendirilmiştir. Olguların yaş, cinsiyet ve tümör lokalizasyonu bilgileri kaydedilmiştir. Olguların %56,3'ünde Kirsten Ras Onkogen Homolog Gen, %7,1'inde Nöroblastom RAS Viral Onkogen Homolog, %7,1'inde V-Raf Murine Sarkom Viral Onkogen Homolog B1, %25,8'inde Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutasyonu izlenmiştir. Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutasyonu izlenen 19 olguda Kirsten Ras Onkogen Homolog Gen mutasyonunun saptanmıştır ve 2 olguda V-Raf Murine Sarkom Viral Onkogen Homolog B1 ve Nöroblastom RAS Viral Onkogen Homolog, 1 olguda Kirsten Ras Onkogen Homolog Gen ve Nöroblastom RAS Viral Onkogen Homolog çift mutayonlarının görülmüştür, bununla birlikte Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutasyonu izlenen 4 olguda Kirsten Ras Onkogen Homolog Gen mutasyonu izlenen 1 olguda bu genlerde farklı ekzon bölgelerinde senkron mutasyonlar görülmüştür. Bu bulgular kolorektal karsinomların sergiledikleri heterojen moleküler özellikleri göstermiştir. Elde edilen bulgulara göre, Kirsten Ras Onkogen Homolog Gen ve V-Raf Murine Sarkom Viral Onkogen Homolog B1 mutasyonları ile az diferansiye küme oluşumu arasında istatistiksel anlamlı ilişki saptanmasa da, Kirsten Ras Onkogen Homolog Gen ve V-Raf Murine Sarkom Viral Onkogen Homolog B1 mutasyonlarının az diferansiye küme oluşumunu 4 kat arttırdığı bulunmuştur. Nöroblastom RAS Viral Onkogen Homolog mutasyonu ile derece 2 az diferansiye küme oluşumu arasında istatistiksel olarak anlamlı ilişki saptanmıştır. Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutasyonu ile düşük stroma oranı arasında istatistiksel olarak anlamlı ilişki saptanmıştır. Sonuç olarak çalışmamızda saptadığımız , kolorektal karsinomların sinyal yollarında yer alan birden fazla mutasyonunun, tümörün klinik ve morfolojik heterojenitesine, hedefe yönelik tedavide kullanılan ilaçlara yanıta olan yansımalarının belirlenebilmesi için geniş vaka serileri ile yapılacak klinik çalışmalara ihtiyaç vardır. Az diferansiye küme, tümör tomurcuğu ve tümör mikroçevresi özellikleri gibi tümörün epitelyal mezenkimal geçiş ilişkili invaziv karakterini yansıtan fenotipik özelliklerin moleküler profilinin tanımlanmasının, hedefe yönelik tedavide innovatif gelişmeler sağlayabilmesi için moleküler yöntemlerin kullanılacağı daha geniş vaka serileri ile yapılacak klinik çalışmalara ihtiyaç vardır.
Colorectal carcinomas are the most common cancer of the gastrointestinal tract and one of the most important causes of cancer-related death. Colorectal cancers are the third most common cancer among all cancer types in men and women, and most of them are sporadic. Most colorectal carcinomas are adenocarcinomas. In our study, 112 cases were included in the study in order to compare Kirsten Ras Oncogen Homolog Gene, V-Raf Murine Sarcoma Viral Oncogene Homolog B1, Neuroblastoma RAS Viral Oncogene Homologue, Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutations and clinicopathological parameters in colorectal cancers with next generation sequancing method. In Hematoxylen & Eosin stained slides of the cases, tumor budding, poorly differentiated clusters, tumor stroma ratio, inflammatory cell reaction, extra/intramural vascular invasion, perineural invasion, lymphovascular invasion, histological tumor subtype, histological tumor grade, primary tumor and lymph node stage, mucinous component presence was evaluated. Age, gender and tumor localization information of the cases were recorded. Kirsten Ras Oncogen Homolog Gene mutations were observed in 56.3%, Neuroblastoma RAS Viral Oncogene Homologue in 7.1%, V-Raf Murine Sarcoma Viral Oncogene Homolog B1 in 7.1%, and Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutations in 25.8% of cases. Kirsten Ras Oncogen Homolog Gene mutation was detected in 19 cases with PIK3CA mutation, V-Raf Murine Sarcoma Viral Oncogene Homolog B1 and NRAS double mutations were observed in 2 cases, and Kirsten Ras Oncogen Homolog Gene and Neuroblastoma RAS Viral Oncogene Homologue double mutations were observed in 1 case. However, synchronous mutations in these genes in different exon regions were observed in 4 cases with Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutation in 1 case with Kirsten Ras Oncogen Homolog Gene mutation. These findings demonstrated the heterogeneous molecular properties exhibited by colorectal cancers. According to the findings, although no statistically significant relationship was found between Kirsten Ras Oncogen Homolog Gene and V-Raf Murine Sarcoma Viral Oncogene Homolog B1 mutations and poorly differentiated cluster formation, it was found that Kirsten Ras Oncogen Homolog Gene and V-Raf Murine Sarcoma Viral Oncogene Homolog B1 mutations increased poorly differentiated cluster formation 4-fold. A statistically significant correlation was found between Neuroblastoma RAS Viral Oncogene Homologue mutation and grade 2 poorly differentiated cluster formation. A statistically significant correlation was found between Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutation and low stroma rate. In conclusion, clinical studies with large case series are needed to determine the reflections of multiple mutations in the signal pathways ofcolorectal carcinomas, which we detected in our study, on the clinical and morphological heterogeneity of the tumor and the response to drugs used in targeted therapy. Clinical studies with larger case series using molecular methods are needed in order to define the molecular profile of the phenotypic features reflecting the invasive character of the tumor associated with epithelial mesenchymal transition, such as poorly differentiated cluster, tumor budding and tumor microenvironment features, to enable innovative developments in targeted therapy.
Colorectal carcinomas are the most common cancer of the gastrointestinal tract and one of the most important causes of cancer-related death. Colorectal cancers are the third most common cancer among all cancer types in men and women, and most of them are sporadic. Most colorectal carcinomas are adenocarcinomas. In our study, 112 cases were included in the study in order to compare Kirsten Ras Oncogen Homolog Gene, V-Raf Murine Sarcoma Viral Oncogene Homolog B1, Neuroblastoma RAS Viral Oncogene Homologue, Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutations and clinicopathological parameters in colorectal cancers with next generation sequancing method. In Hematoxylen & Eosin stained slides of the cases, tumor budding, poorly differentiated clusters, tumor stroma ratio, inflammatory cell reaction, extra/intramural vascular invasion, perineural invasion, lymphovascular invasion, histological tumor subtype, histological tumor grade, primary tumor and lymph node stage, mucinous component presence was evaluated. Age, gender and tumor localization information of the cases were recorded. Kirsten Ras Oncogen Homolog Gene mutations were observed in 56.3%, Neuroblastoma RAS Viral Oncogene Homologue in 7.1%, V-Raf Murine Sarcoma Viral Oncogene Homolog B1 in 7.1%, and Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutations in 25.8% of cases. Kirsten Ras Oncogen Homolog Gene mutation was detected in 19 cases with PIK3CA mutation, V-Raf Murine Sarcoma Viral Oncogene Homolog B1 and NRAS double mutations were observed in 2 cases, and Kirsten Ras Oncogen Homolog Gene and Neuroblastoma RAS Viral Oncogene Homologue double mutations were observed in 1 case. However, synchronous mutations in these genes in different exon regions were observed in 4 cases with Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutation in 1 case with Kirsten Ras Oncogen Homolog Gene mutation. These findings demonstrated the heterogeneous molecular properties exhibited by colorectal cancers. According to the findings, although no statistically significant relationship was found between Kirsten Ras Oncogen Homolog Gene and V-Raf Murine Sarcoma Viral Oncogene Homolog B1 mutations and poorly differentiated cluster formation, it was found that Kirsten Ras Oncogen Homolog Gene and V-Raf Murine Sarcoma Viral Oncogene Homolog B1 mutations increased poorly differentiated cluster formation 4-fold. A statistically significant correlation was found between Neuroblastoma RAS Viral Oncogene Homologue mutation and grade 2 poorly differentiated cluster formation. A statistically significant correlation was found between Fosfatidilinozitol-4,5-bifosfat 3-kinaz katalitik subunit alfa mutation and low stroma rate. In conclusion, clinical studies with large case series are needed to determine the reflections of multiple mutations in the signal pathways ofcolorectal carcinomas, which we detected in our study, on the clinical and morphological heterogeneity of the tumor and the response to drugs used in targeted therapy. Clinical studies with larger case series using molecular methods are needed in order to define the molecular profile of the phenotypic features reflecting the invasive character of the tumor associated with epithelial mesenchymal transition, such as poorly differentiated cluster, tumor budding and tumor microenvironment features, to enable innovative developments in targeted therapy.
Açıklama
Tıpta Uzmanlık
Anahtar Kelimeler
Patoloji, Pathology
