Aims: The most frequently mutated genes in pancreatic ductal adenocarcinoma (PDAC) are KRAS, TP53, CDKN2A/p16, and SMAD4/DPC4. These gene mutations affect disease specific survival (DSS) and progression free survival (PFS). Our aim is to evaluate the impact of SMAD4/DPC4, CDKN2A/p16 and TP53 expression on survival of patients who received a pancreatectomy with arterial resection (P-Ar) because of a locally advanced PDAC (LA-PDAC). Methods: A retrospective study on P-Ar performed for LA-PDAC between 2000 and 2017 was conducted. Post-operative deaths were excluded. The genes status was immunohistochemically assessed and the differences in term of DSS and PFS between patients with positive and negative status were calculated by using Kaplan– Meier curves and Log-rank test. The relationship between preoperative features and genes expression was evaluated by using logistic regression. Results: A total of 38 patients were eligible for this study. The superior mesenteric artery was resected in 16 (42.1%) patients and the celiac axis/hepatic artery in 26 (68.4%) patients. Median DSS and PFS were of 25.3 (14.2–74) months and 12.8 (10.3–22) months, respectively. Abnormal immunolabeling of TP53 was present in 21 (55.2%) PDACs. Loss of p16 and SMAD4 was identified in 23 (60.5%) and 22 (57.9%) PDACs, respectively. DSS and PFS were higher in patients with positive SMAD4, positive P53 and loss of p16 (Table 1). When the loss of SMAD4 was associated with an abnormal labelling of p53 and the expression of p16 concurrently, both DSS (13.3 vs. 26.7 months, p = 0.03*) (Fig. 1) and PFS (10.3 vs 15 months, p = 0.01*) were statistical significantly worse. Preoperative level of Ca 15.3 was correlated with the expression of SMAD4/DPC4 (p = 0.01*).
PROGNOSTIC VALUE OF TP53, CDKN2A/P16 AND SMAD4/ DPC4 IN LOCALLY ADVANCED, BUT RESECTED, PANCREATIC CANCER
N. Napoli;E. F. Kauffmann;C. Cacace;F. Menonna;A. Cacciato Insilla;F. Vistoli;D. Caramella;D. Campani;U. Boggi
2020-01-01
Abstract
Aims: The most frequently mutated genes in pancreatic ductal adenocarcinoma (PDAC) are KRAS, TP53, CDKN2A/p16, and SMAD4/DPC4. These gene mutations affect disease specific survival (DSS) and progression free survival (PFS). Our aim is to evaluate the impact of SMAD4/DPC4, CDKN2A/p16 and TP53 expression on survival of patients who received a pancreatectomy with arterial resection (P-Ar) because of a locally advanced PDAC (LA-PDAC). Methods: A retrospective study on P-Ar performed for LA-PDAC between 2000 and 2017 was conducted. Post-operative deaths were excluded. The genes status was immunohistochemically assessed and the differences in term of DSS and PFS between patients with positive and negative status were calculated by using Kaplan– Meier curves and Log-rank test. The relationship between preoperative features and genes expression was evaluated by using logistic regression. Results: A total of 38 patients were eligible for this study. The superior mesenteric artery was resected in 16 (42.1%) patients and the celiac axis/hepatic artery in 26 (68.4%) patients. Median DSS and PFS were of 25.3 (14.2–74) months and 12.8 (10.3–22) months, respectively. Abnormal immunolabeling of TP53 was present in 21 (55.2%) PDACs. Loss of p16 and SMAD4 was identified in 23 (60.5%) and 22 (57.9%) PDACs, respectively. DSS and PFS were higher in patients with positive SMAD4, positive P53 and loss of p16 (Table 1). When the loss of SMAD4 was associated with an abnormal labelling of p53 and the expression of p16 concurrently, both DSS (13.3 vs. 26.7 months, p = 0.03*) (Fig. 1) and PFS (10.3 vs 15 months, p = 0.01*) were statistical significantly worse. Preoperative level of Ca 15.3 was correlated with the expression of SMAD4/DPC4 (p = 0.01*).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
