Purpose: <p>Patients with Pancreatic neuroendocrine neoplasm grade-3 (PanNEN-G3) show variable responses to platinum-based chemotherapy. Recent studies indicated that PanNEN-G3 includes well-differentiated neuroendocrine tumor with G3 (NET-G3). Here, we examined the clinicopathological and molecular features of PanNEN-G3 and assessed the responsiveness to chemotherapy and survival.</p> Experimental Design: 100 patients with PanNEN-G3 were collected from 31 institutions, and after central review characteristics of each histological subtype (NET-G3 versus pancreatic neuroendocrine carcinoma (NEC-G3)) were analyzed, including clinical, radiological, and molecular features. Factors that correlate with response to chemotherapy and survival were assessed. <br /><br />Results: <p>70 patients analyzed included 21 NETs-G3 (30%) and 49 NECs-G3 (70%). NET-G3 showed lower Ki67-LI (median 28.5%), no abnormal Rb expression (0%), and no mutated KRAS (0%), whereas NEC-G3 showed higher Ki67-LI (median 80.0%), Rb loss (54.5%), and KRAS mutations (48.7%). Chemotherapy response rate (RR), platinum-based chemotherapy RR, and prognosis were significantly different between NET-G3 and NEC-G3. Chemotherapeutic outcomes were worse in NET-G3 (P<0.001). When we stratified PanNEN-G3 with Rb and KRAS, PanNENs-G3 with Rb loss and those with mutated KRAS showed significantly higher RRs to platinum-based chemotherapy than those without (Rb loss, 80% versus normal Rb, 24%, p=0.006; mutated KRAS, 77% versus wild-type, 23%, p=0.023). Rb was a predictive marker for response to platinum-based chemotherapy even in NEC-G3 (P=0.035).</p> Conclusions: <p>NET-G3 and NEC-G3 showed distinct clinicopathological characteristics. Notably, NET-G3 does not respond to platinum-based chemotherapy. Rb and KRAS are promising predictors of response to platinum-based chemotherapy for PanNEN-G3, and Rb for NEC-G3.
http://ift.tt/2qoTHHW
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου