The Association Between Tumor Necrosis Factor-Alpha (Tnf-Α) Expression and Molecular Subtype in Oral Cancer

Öz

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral cavity and the development and progression of this tumor is due to the accumulation of genetic alterations. On the other hand, tumor necrosis factor alpha (TNF-α) is known to play an important role in tumor invasion. The aim of this study was to detect genetic alterations in oral cancer and to investigate the possible relationship between molecular subtype, inflammation and TNF-α expression. The study was conducted on 39 tissue samples, 25 of which were diagnosed as OSCC. All were subjecte to DNA isolation from paraffin embedded blocks and followed by next-generation sequencing (NGS) platform that examined the complete coding sequence of in 28 cancer-related genes. TNF-α expression in tissues was determined by immunohistochemical studies. Inflammation scoring was performed in hemotoxylin & eosin sections for each case. Eighteen of 25 (72%) OSCC cases showed alterations in at least in one gene. P53 was the most frequent altered gene in all lesions. Three or more gene alterations were detected in 3 of all cases (%12). TNF-α was overexpressed in tumors with mutation. The mutation spectrum revealed by the next-generation sequence analysis (NGS) suggests that genetic alterations in OSCC are diverse and complex. The results of the study suggest that there is a relationship between genetic alterations and inflammation/TNF-α expression.

Anahtar Kelimeler

• Next-generation sequence analysis, NGS, oral cancer, TNF-α

Oral Kanserde Tümör Nekrozis Faktör-Alfa (Tnf-α) Ekspresyonunun Moleküler Subtipleme ile İlişkisi

Öz

Oral kavitenin en sık izlenen malign tümörü olan oral skuamöz hücreli karsinomun (OSHK) gelişmesi ve ilerlemesi, genetik alterasyonların birikmesinden kaynaklanmaktadır. Diğer taraftan Tümör nekrozis faktör-alfa (TNF-α)'nın tümör invazyonunda önemli rol oynadığı da bilinmektedir. Bu çalışmanın amacı, oral kanserdeki genetik alterasyonları saptayıp, moleküler alttipleme ile inflamasyon ve TNF- α ekspresyonu arasındaki ilişkiyi incelemektir. Çalışma, 25’i OSHK tanısı almış toplam 39 doku örneği üzerinde gerçekleştirildi. Parafine gömülü bloklardan elde edilen DNA izolasyonunu takiben, 28 adet kanser ilişkili gene ait genetik değişiklikler yeni nesil dizileme analizi (NGS) ile tayin edildi. Dokulardaki TNF- α ekspresyonu immünhistokimyasal çalışmalar ile tayin edildi. İnflamasyon skorlaması, her vaka için hemotoksilen-eosin kesitlerde yapıldı. Toplam 25 adet OSHK vakasının 18’inde (%72) bir veya birden fazla mutasyon izlenmiştir. En sık mutasyonu görülen gen, P53 geni olarak saptanmıştır. Tüm vakalardan 3 tanesi (%12) üç ve daha fazla gen mutasyonu göstermiştir. TNF- α ekspresyonu mutasyon saptanan tümörlerde daha fazla izlenmiştir. Yeni nesil dizileme analizi (NGS) ile ortaya çıkan mutasyon spektrumu, OSHK'deki genetik değişikliklerin ne kadar çeşitli ve karmaşık olduğunu göstermektedir. Çalışma sonuçları genetik değişiklikler ile inflamasyon ve TNF-α ekspresyonu arasında ilişki olduğunu düşündürmektedir. OSHK’nin tanı ve tedavisinde histopatolojik incelemenin yanı sıra, genetik alterasyonları da ortaya koymak hedefe yönelik tedavide yeni alternatifler sunacaktır.

Anahtar Kelimeler

• oral cancer
• yeni nesil dizileme
• TNF-a

Kaynakça

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