Molecular Comparison between Intraductal Tubulopapillary Neoplasms and Intraductal Tubular Adenomas of the Pancreas Indicates Their Distinctive Nature
Hiroshi Yamaguchi, Michio Shimizu, Yuko Kuboki, Toru Furukawa. Saitama International Medical Center, Saitama Medical University, Hidaka, Japan; Tokyo Women's Medical University, Tokyo, Japan
Background: Intraductal tubulopapillary neoplasm (ITPN) is composed of tubulopapillary masses with high-grade atypia in the pancreatic duct. Intraductal tubular adenoma (ITA) is composed of tubular glands mimicking pyloric glands with low-grade atypia. Some may consider that ITA could be a benign counter part of ITPN, however, whether ITPN and ITA are distinctive or not is not fully assessed. In this study, we compared molecular features between ITPNs and ITAs to know their distinct or similar nature.
Design: Formalin-fixed, paraffin-embedded tissues of 14 ITPNs and 15 ITAs were investigated in this study. Foci of tumor and normal tissues were dissected separately from serial sections under microscopic guidance. Genomic DNA was extracted and somatic mutations in exons 10 and 21 of PIK3CA, exons 8 and 9 of GNAS, exons 2 and 3 of KRAS, and exon 15 of BRAF were analyzed.
Results: Somatic mutations in PIK3CA were found in 3 of 14 ITPNs (21.4%) but not in any of ITAs (P = 0.0996; Fisher exact test). In contrast, mutations in GNAS were found in none of the ITPNs but were found in 9 of 15 ITAs (60.0%) (P < 0.001; Fisher exact test). Mutations in KRAS were detected in 1 of 14 ITPNs (7.1%) and 12 of 15 ITAs (80.0%) (P<0.001; Fisher exact test). BRAF mutation was found in 1 ITPNs but none of ITAs.
Conclusions: These results clearly indicate that ITPNs and ITAs are molecularly distinctive from each other, which suggests that ITPNs do not evolve from ITAs. Furthermore, the molecular features of ITAs were similar to those reported in IPMNs, i.e., prevailed mutations in GNAS and KRAS, which is consistent with the renewed (2010) World Health Organization classification system for intraductal neoplasms of the pancreas that describes that intraductal neoplasms are classified into IPMNs and ITPNs, and ITA is a variant of IPMNs.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 161, Tuesday Afternoon