Pancreatic Intraepithelial Neoplasia (PanIN) and the Association With Recurrence of Pancreatic Adenocarcinoma

Refining the Molecular Progression From Intraductal to Invasive Pancreatic Cancer: Correlating Genetic Profiles and Clinicopathological Phenotypes in Sporadic and Familial Pancreatic Adenocarcinoma

The research purpose of this project is to create a registry, and blood and tissue bank for individuals at high-risk for pancreatic cancer. We plan to conduct histopathological and molecular analysis of resected pancreatic tissue prospectively collected from a cohort of pancreatic cancer patients.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer

Detailed Description

Pancreatic cancer is the fifth leading cause of cancer-related death in the United States. In order to improve outcomes of this disease, significant research efforts have focused on understanding the changes that occur in the pancreas prior to tumor occurrence. The types of changes most often associated with tumor have been named pancreatic intraepithelial neoplasia (PanIN). It is not yet clear how to identify the PanIN lesions most likely to develop into cancer and the length of time required for this progression. In order to evaluate these questions, we are interested in examining the microscopic and genetic characteristics of PanIN lesions in two "high-risk" patients: 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 surgical specimens from these patients will be evaluated by a pathologist for evidence of widespread PanIN lesions. In addition, PanIN lesions will be tested for abnormalities in several major genes that are known to be important in pancreatic cancer.

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who are identified by a clinician as having either 1) a strong family history of pancreatic cancer; or 2) evidence (radiological or pathological) of local tumor recurrence following surgical resection, will be included in the study.

Description

Inclusion Criteria:

• Tissue-confirmed diagnosis of pancreatic adenocarcinoma.
• Underwent surgical resection for adenocarcinoma at Columbia-Presbyterian Medical Center with pathologically negative surgical margins.
• Enrolled in our Pancreatic Cancer Registry and Tissue Bank protocol (AAAA-6154).
• Have at least 2 relatives (of whom one must be first-degree relative) with pancreatic cancer, or have been diagnosed with a a genetic syndrome which is associated with pancreatic cancer (among the included syndromes include BRCA1/2, FAMMM, Peutz-Jeghers, HNPCC, Hereditary Pancreatitis) -OR- Have radiological or pathological (fine needle aspirate or surgical biopsy) evidence of local tumor recurrence following surgery.

Exclusion Criteria:

• Metastatic disease discovered at presentation or on recurrence (exception is the familial PDC patients)
• Positive surgical margins.
• Lack of clinical followup at one year following surgery

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.
Recurrence patients; Patients who underwent surgery for pancreatic cancer and developed tumor recurrence after surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with histological features of PanIN lesions assessed	Distinctive histological features of PanIN within surgical specimens of our two study groups will be assessed by pathologists.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of clonality multifocal PanIN lesions	Using microarray-based comparative genomic hybridization (aCGH) to evaluate the samples.	1 year
Evaluation of Recurrence Mechanism in PDC	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.	1 year

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Cold Spring Harbor Laboratory

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 18, 2009
• Primary Completion (ACTUAL): April 27, 2021
• Study Completion (ACTUAL): April 27, 2021

Study Registration Dates

• First Submitted: October 11, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (ESTIMATE): October 13, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2021
• Last Update Submitted That Met QC Criteria: June 9, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Pancreatic intraepithelial neoplasia (PanIN); Recurrence of pancreatic cancer; Field Effect; Genetic mutations in pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Adenocarcinoma; Pancreatic Neoplasms
• Other Study ID Numbers: AAAD5381

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No