Rapid Autopsy Program for Pancreatic Carcinoma: Correlation of Histologic Subtypes and Pattern of Spread with Mucin Phenotype and Molecular Markers
Erin M Linde, Neeley A Remmers, Dominick J DiMaio, Judy M Anderson, Michael A Hollingsworth, Audrey J Lazenby. University of Nebraska Medical Center, Omaha, NE; University of Nebraksa Medical Center, Omaha, NE
Background: Pancreatic ductal adenocarcinoma (PDA) is the 4th leading cause of cancer-related death with 1 and 5 year survival rates of 20-40% and 5%, respectively. Only 20% of patients are surgical candidates and 70% have metastatic disease at resection. Histology alone does not adequately predict biologic behavior or response to therapy. Novel molecular markers may aid in early diagnostic and therapeutic options. This study reports the morphologic variation and metastatic pattern of PDA in decedents enrolled in our rapid autopsy program (RAP) with correlation to mucin phenotype and other molecular markers associated with tumor progression.
Design: A trunk-only autopsy was performed via a modified Virchow method within 3 hours of death. Tissue was submitted for histopathology and snap frozen for the tissue bank. Photographs were taken to document extent of spread. All autopsy slides and reports were reviewed for histologic features and metastatic patterns. Tissues were analyzed by immunohistochemistry (IHC) for the expression of 18 different mucins and associated glycans previously linked with PDA. IHC staining intensity and percentage of positive cells was scored, converted to a heat map, and compared to histology and pattern of metastatic spread.
Results: Forty-eight patients with PDA were autopsied (2002-2011, mean postmortem interval 2.1 hrs). Degree of differentiation was well (5), moderately (18), and poorly (13) differentiated, and undifferentiated (4); no clear association of differentiation with mucin types was seen. Signet ring cell features (7) was associated with decreased LewisX expression. Clear cell change (8) was not correlated with a particular mucin pattern. Two major patterns of intra-abdominal spread were noted: serosal studding (innumerable, minute foci of minimally invasive tumor) and carcinomatosis (diffuse large invasive tumor foci). Cases with serosal studding (10) had increased expression of MUCs 17, 6, 5AC, 7, and 4 (mild) when compared to carcinomatosis (6), in which the expression of MUCs 17, 7, and 6 was lost.
Conclusions: 1. Two distinct patterns of intra-abdominal spread of tumor were identified: serosal studding and carcinomatosis. These correlated with distinct mucin phenotypes.
2. Signet ring cell features correlate with a decrease in Lewisx expression.
3. No correlation with clear cell change or degree of differentiation was seen with mucin phenotype.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 6, Wednesday Morning