Usefulness of adding genomic mutation information for diagnosis of horizontal cholangiocarcinoma progression

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16439
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Takahashi Hiroyuki 旭川医科大学, 医学部, 助教 (10516503)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 胆管癌 / 切除断端診断

Outline of Final Research Achievements

In this targeted sequencing of resected cholangiocarcinoma specimens, some type of genetic mutation was detected in 91% of cases. TP53 mutations were found in 78%. Immunostaining for p53 in tumors showed a high concordance between TP53 mutations and p53 staining patterns.
Sequencing of truncal segments showed that all truncal positive cases had a genetic mutation in the bile duct truncus that was consistent with the primary tumor, and all had TP53 mutations. In 40% of the truncus-negative cases, a genetic mutation was found in the bile duct transection, with the same genetic mutation as the main tumor in all but one case, and all but two cases were TP53 mutation-positive. Anastomotic recurrence was observed in two cases of negative margins, both of which had genetic mutations in the margins.

Free Research Field

胆管癌

Academic Significance and Societal Importance of the Research Achievements

胆管癌では胆管炎や胆道ドレナージに伴う再生異型やスキップあるいは多発病変が存在する可能性があり、術中の迅速診断、さらに永久標本をもってしても切除断端の判定に苦慮する場合がある。
本研究では、胆管がんはTP53変異を持つことが多くターゲットシークエンスで検出することができること、断端陰性症例でも、TP53等の変異が検出されることがあり、TP53変異とp53免疫染色は相互によく関連し、断端評価に利用できることが示された。未だ周術期リスクの高い胆管癌根治手術において、根治のための過不足ない手術を施行するための確実な断端診断は必須事項であり、ゲノム情報の付加は正診率向上に寄与する可能性がある。