Pancreatic Intraepithelial Neoplasia (PanIN) and the Association With Recurrence of Pancreatic Adenocarcinoma
Pre-invasive intraepithelial neoplasms (PanIN) have been identified as precursor lesions to pancreatic cancer. While there is growing evidence supporting PanIN's genetic links to pancreatic adenocarcinoma, the natural history of these lesions has not been well-established. Thus, through this study, the investigators are interested in examining the microscopic and genetic characteristics of PanIN lesions in two "high-risk" patient groups: 1)patients who underwent surgery for pancreatic cancer and developed tumor recurrence after surgery and 2) patients with a strong family history of pancreatic cancer or with a genetic syndrome that puts them at risk for pancreas cancer.
The investigators hypothesize that field carcinogenesis, neoplasia in surrounding tissue around the primary tumor site, is an important mechanism of local recurrence in sporadic pancreatic adenocarcinoma and of primary tumorigenesis in familial pancreatic cancer.
|Study Design:||Observational Model: Case Control
Time Perspective: Retrospective
|Official Title:||Refining the Molecular Progression From Intraductal to Invasive Pancreatic Cancer: Correlating Genetic Profiles and Clinicopathological Phenotypes in Sporadic and Familial Pancreatic Adenocarcinoma|
- Primary Outcome: Distinct histological features of PanIN lesions [ Time Frame: 1 year ] [ Designated as safety issue: No ]Our first aim is to assess for distinctive histological features of PanIN within surgical specimens of our two study groups.
- Secondary Outcome: Clonality of Multifocal PanIN Lesions [ Time Frame: 1 year ] [ Designated as safety issue: No ]Our secondary aim is to evaluate clonality of multifocal PanIN lesions by utilizing microarray-based comparative genomic hybridization (aCGH).
- Secondary Outcome: Evaluation of Recurrence Mechanism in PC [ Time Frame: 1 year ] [ Designated as safety issue: No ]aCGH will also be utilized to evaluate recurrence mechanism in a set of cases in which both original tumor and recurrence tumor was resected, allowing for clonal origins to be evaluated.
Biospecimen Retention: Samples With DNA
- Tissue: Pancreatic resection specimens will be obtained from our Pancreatic Cancer Tissue Bank and evaluated by a single pathologist, blinded to patients' clinical information. Specimens will be examined for PanIN lesions, specifically number and grade of lesions, the presence of multifocality and lesion location in relation to tumor.
- Molecular Analysis: In patients with multifocal PanIN disease outside tumor location, molecular analysis will be conducted to determine clonality of these PanIN lesions. In any patient who underwent a second resection for recurrent Pancreatic ductal adenocarcinoma , the recurrent tumor will also be studied. All neoplastic lesions of interest will be laser-microdissected from paraffin-embedded slides.
- ROMA analysis: Genomic DNA from PanIN lesions and tumor will be isolated, using representational oligonucleotide microarray analysis (ROMA) or somatic mutation analysis. ROMA analysis will be performed by Cold Spring Harbor Laboratory.
|Study Start Date:||August 2008|
|Estimated Study Completion Date:||May 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Family History patients
Patients with a strong family history of pancreatic cancer or with a genetic syndrome that puts them at risk for pancreas cancer.
Patients who underwent surgery for pancreatic cancer and developed tumor recurrence after surgery
A control Pancreatic ductal adenocarcinoma (PDC) patient from the Registry will also be identified for each study patient, matched by age, stage, history of neoadjuvant chemotherapy/radiation and smoking status.
Pancreatic adenocarcinoma (PC) is the fourth leading cause of cancer-related death in the United States.Despite advances in chemotherapeutics and surgical care, the prognosis for PC patients remains dismal, even following surgery with curative intent. In order to improve outcomes, the best hope will be to target preinvasive PanIN lesions for screening and therapy. Prior to this, however, the natural history of PanIN lesions needs to be better elucidated. A novel model to study PanIN progression is by examination of cases of local recurrence following surgical resection. We have previously reported our findings from histopathological review of such cases. Compared to matched controls, locally-recurrent PC patients were significantly more likely to exhibit a pattern of multifocal, diffuse PanIN in their original resection tissue. This is similar to the pattern of multifocal PanIN that has been demonstrated from small prospective screening studies of familial PC kindreds
These analyses support our hypothesis that field carcinogenesis may be an important mechanism in PC. The objective of our study is to evaluate for pathological and molecular evidence of a field effect in locallyrecurrent and familial PC. Our first aim is to assess for distinctive histological features of PanIN within surgical specimens of our two study groups. Secondly, clonality of multifocal PanIN will be assessed utilizing microarraybased comparative genomic hybridization (aCGH). Finally, aCGH will also be utilized to evaluate recurrence mechanism in a set of cases in which both original tumor and recurrence tumor was resected, allowing for clonal origins to be evaluated.
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Principal Investigator:||Wendy K Chung, MD||Columbia University|