Progression modellings in pancreas carcinoma and pancreatic intraepithelial neoplasia

Öz

Pancreatic ductal adenocarcinomas (PDACs) make up more than 90%. Pancreatic carcinoma (PC) is the fourth most common cause of death in both genders. The most common PC types can be classified as PDAC. Rare types of ductal adenocarcinoma are; intraductal papillary-mucinous carcinomas, mucinous cystic neoplasia, medullary carcinoma, and other rare types. While 5-year survival rates of PDACs are less than 10% pancreatic precursor lesions, and carcinogenesis mechanisms are studied. It is accepted that PDACs develop by sequential tumor progression. Sequential preinvasive stages are well defined and morphologically different. Pancreatic intraepithelial neoplasia (PanIN) generally can’t be clinically identified, but still are the most common precursor of invasive ductal adenocarcinoma. For this reason, PanINs are of interest for PC diagnosis. In a simplified classification PanIN-1 A/B and PanIN-2 are low-grade, PanIN-3 is high-grade PanIN. The current progression model depending on the analysis of precursor lesions has two predictions: 1) PC develops according to specific alternations in genetic (KRAS> CDKN2A> TP53/SMAD4), and 2) as every alternation occurs independently PC development is stepwise. Intraductal papillary mucinous neoplasia (IPMN) is a separate entity of pancreatic cyst; an intraductal epithelial neoplasia secreting mucin, originating from the pancreatic duct, grossly visible (>5mm). Mucinous cystic neoplasia (MCN) is the rarest precancerous lesion of the pancreas. They are slow-growing cystic tumors and do not originate from the pancreatic ductal system. MCNs have dysplasia and focality. High-risk patients such as PanIN, MCN, and IPMN which would benefit from screenings made for premalignant disorders should be identified, though to date there is no acceptable screening test. the only curative treatment option available is radical surgical resection. Mechanism-based treatment options will be able in the future.

Anahtar Kelimeler

• PanIN
• Pancreas cancer
• Progression models

Pankreas kanserlerinde progresyon modellemeleri ve pankreatik intraepitelyal neoplazi

Öz

Pankreatik duktal adenokarsinomlar (PDAC) pankreas kanserlerinin %90’dan fazlasını oluşturur. Pankreas kanseri (PK) her iki cinsiyette de en sık dördüncü ölüm nedenidir. En sık PK türleri PDAC olarak sınıflanabilir. Duktal tip olup daha seyrek görülen duktal adenokarsinom varyantları; intraduktal papiller-musinöz kanserlerdir, müsinöz kistik neoplazi, medüller karsinom ve diğer nadir türler vardır. PDAC’lerin 5 yıllık sağ kalımının %10 un altında olması nedeni ile pankreatik prekürsör lezyonların çalışılması ile karsinogenesin mekanizmaları aydınlatılmaya çalışılmaktadır. Günümüzde PDAC’un basamaklı tümör progresyonu şeklinde geliştiği kabul edilmektedir. Ardışık preinvaziv evreler oldukça iyi tanımlanmıştır ve morfolojik olarak farklıdır. Pankreatik intraepitelyal neoplaziler (PanIN) genelde klinik olarak tanınamazlar, ancak yine de invaziv duktal adenokarsinomun en sık öncüleridir. Bu nedenle PanIN’ler pankreas kanseri tanısında ilgi kaynağı olmuştur. Sadeleştirilmiş bir sınıflamada PanIN-1A/B ve PanIN-2’yi low grade PanIN, PanIN-3 high grade olarak ayrılmıştır. Prekürsör lezyonların analizine dayanan mevcut progresyon modeli olan PanIN’in iki öngörüsü vardır: 1) PK genetik değişikliklerde özel bir sıralama ile oluştuğudur (KRAS> CDKN2A> TP53/SMAD4) ve 2) her bir değişim bağımsız olarak oluştuğundan PK gelişimi kademelidir. İntraduktal papiller müsinöz neoplazi (IPMN) pankreatik kistik hastalığın farklı bir antitesidir, gros olarak görülebilen (>5mm) pankreatik dukt hücrelerinden köken alan müsin salgılayan intraduktal epitelyal neoplazidir. İntestinal ve intestinal olmayan IPMN’lerin farklı biyolojik yolaklar izlediğine dair kanıtlar vardır. Tek bir IPMN birden fazla epitel tipi içerebilir. Müsinöz kistik neoplaziler (MCN) pankreasın en nadir kanser öncüsü lezyonlarıdır. Yavaş büyüyen kistik tümörlerdir, pankreasın duktal sisteminden köken almazlar. MCN’de displazi ve fokalite vardır. Premalign durumların tespiti için yapılacak taramalardan fayda görebilecek PanIN, MCN ve IPMN gibi yüksek riskli hastaların belirlenmesi gereklidir, ancak kabul edilebilir bir tarama testi henüz yoktur. Günümüzde tek küratif tedavi opsiyonu radikal yaklaşımlı cerrahi rezeksiyondur. Mekanizma bazlı tedavi seçenekleri gelecekte görülecektir.

Anahtar Kelimeler

• Pankreas kanseri
• Progresyon modellemeleri
• PanIN

Kaynakça

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