Molecular Analysis of Pancreatic Ductal Carcinoma and Pancreatic Intraepithelial Neoplasia (PanIN): Does PanIN Represent a Precursor to Invasive Ductal Carcinoma or Secondary Cancerization of Ducts.
Shahid J Bokhari, Jan F Silverman, Sydney D Finkelstein, Alok Mohanty. Allegheny General Hospital, Pittsburgh, PA; RedPath Integrated Pathology, Pittsburgh, PA
Background: PanIN is seen frequently associated with invasive ductal carcinoma of the pancreas in the same specimen, often found adjacent to the foci of invasive ductal carcinoma. PanIN is assumed to be a precursor lesion of invasive ductal carcinoma of the pancreas. However, there is a lack of data in the literature regarding whether PanIN is a definite precursor lesion or represents cancerization of the ducts present in close proximity to the invasive ductal carcinoma. To address this question, we performed comparative mutational profiling of the invasive ductal carcinoma and the adjacent areas with PanIN.
Design: A total of 14 cases of invasive pancreatic ductal carcinoma with associated PanIN were retrieved from the hospital computer system following IRB approval. All cases were confirmed by histology. Tissue sections from 14 pancreatic cancer cases underwent microdissection of both invasive and PanIN foci present adjacent to and at a distance from the invasive tumor. Mutational profiling was performed which consisted of 1) KRAS mutation (1st exon) (DNA sequencing), and 2) allelic imbalance (loss of heterozygosity [LOH]) for a panel of 16 markers situated at 1p, 3p, 5q, 9p, 10q, 17p, 17q, 18q, 21q, and 22q (GeneScan fragment length analysis). For KRAS point mutation, lower threshold of determination of mutant to wild type bases was approximately 10% of mutant to normal. For LOH determination, lower threshold for significant allelic imbalance was at least 2 times the ratio of peak heights for the non-neoplastic DNA for determination of marker informativeness. Mutational clonality (quantitative extent of clonal expansion) was based on the ratio of allele peak heights (LOH) or ratio of mutant and wild type base peaks (KRAS). The mutational profiles between the invasive and PanIN type foci were compared for degree of concordance.
Results: All 14 cases (100%) showed a greater number of cumulative mutations in the foci of invasive ductal carcinoma compared to the cumulative mutations in the foci with PanIN. This finding supports that PanIN is a precursor lesion and not a secondary process arising from cancerization of the ducts by invasive ductal carcinoma.
Conclusions: Our findings support that PanIN is a precursor lesion to invasive ductal carcinoma of the pancreas and does not represent cancerization of the ducts by the invasive ductal carcinoma.
Category: Liver & Pancreas
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 208, Monday Morning