Clinicopathologic Characteristics and Biologic Behavior of Concurrent Pancreatic Ductal Adenocarcinoma (PDAC)
Madelyn Lew, Vicente Morales-Oyarvide, Xiaoyun Liao, Shuji Ogino, Jey-Hsin Chen, Martha B Pitman, Mari Mino-Kenudson. Massachusetts General Hospital, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Brigham and Women's Hospital, Boston, MA; Indiana University, Indianapolis, IN
Background: Intraductal Papillary Mucinous Neoplasm (IPMN), especially of the branch-duct type, carries a risk of not only malignant transformation (invasive IPMN), but can also be associated with development of a separate invasive ductal adenocarcinoma (concurrent PDAC). Several studies have described the clinicopathologic features and biologic behavior of invasive IPMN. In contrast, our understanding of concurrent PDAC is limited, although a recent study has reported equally favorable outcomes of invasive IPMN and concurrent PDAC compared to PDAC not associated with IPMN (conventional PDAC).
Design: The study cohort consisted of 555 patients with conventional PDAC, 17 with concurrent PDAC, and 22 with invasive IPMN with tubular/ductal histology arising in a predominantly branch-duct type IPMN. Clinicopathologic features of the resection specimens and patient survival were compared among these groups. Protein expression of SMAD4 and p53 was analyzed in cases of concurrent PDAC and invasive IPMN with available blocks using tissue microarray.
Results: All concurrent PDACs and invasive IPMNs were associated with gastric-type IPMN. Compared to invasive IPMNs, concurrent PDACs were associated with more proximal location (76% vs. 32%, P = 0.0095), higher incidence of lymphatic (71% vs. 32%, p=0.025) and vascular (65% vs. 27%, P=0.026) invasion, lower 2-year survival (21% vs. 57%), and increased mortality by multivariate analysis (HR: 2.17; 95% CI: 0.92 to 5.15, P = 0.078). Compared to conventional PDACs, concurrent PDACs were associated with older age at presentation (73.4 ± 12.2 vs. 64.6 ± 10.4, P = 0.019) and higher incidence of lymphatic (71% vs. 36%, P = 0.0046) and vascular (65% vs. 34%, P = 0.017) invasion. The 2-year survival of concurrent PDAC was lower than that of conventional PDAC (21% vs. 39%), although the difference was not statistically significant. Loss of SMAD4 was seen in 62% of 13 examined concurrent PDACs, while only 33% of 12 invasive IPMNs lost SMAD4 expression. There was no difference in overexpression of p53 between the 2 groups (54% vs. 58%).
Conclusions: Concurrent PDACs exhibit higher degrees of aggressive pathologic features and increased mortality in comparison with invasive IPMNs and conventional PDACs. Whether the survival disadvantage of concurrent PDACs is conferred by genetic and/or epigenetic alterations, including loss of SMAD4 expression, needs to be elucidated by larger scale studies.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 285, Tuesday Afternoon