Genetic assessment of recurrent pancreatic high-risk lesions in the remnant pancreas: Metachronous multifocal lesion or local recurrence?
| Autor: | Naoki Mochidome, So Nakamura, Yoshihiro Miyasaka, Koji Shindo, Yoshinao Oda, Yasuhisa Mori, Yoshitaka Gotoh, Kenoki Ohuchida, Masafumi Nakamura, Takao Ohtsuka |
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| Rok vydání: | 2018 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Lesion Proto-Oncogene Proteins p21(ras) CDKN2A medicine Multifocal Lesion Neoplasm Humans Survival rate Cyclin-Dependent Kinase Inhibitor p16 Aged Smad4 Protein business.industry High-Throughput Nucleotide Sequencing Neoplasms Second Primary Middle Aged medicine.disease Pancreatic Neoplasms Pancreatectomy Mutation Remnant pancreas Immunohistochemistry Surgery Female Radiology medicine.symptom Neoplasm Recurrence Local Tumor Suppressor Protein p53 business |
| Zdroj: | Surgery. 165(4) |
| ISSN: | 1532-7361 |
| Popis: | Background It is difficult to determine whether a second high-risk lesion, including pancreatic ductal adenocarcinoma or high-grade pancreatic intraepithelial neoplasm, is a metachronous multifocal lesion or represents local recurrence after resection of the first high-risk lesion. This study attempts to clarify the characteristics of second high-risk lesions in the remnant pancreas using genetic analyses. Methods Clinicopathologic data were collected from 12 patients who underwent pancreatectomy for a second high-risk lesion in the remnant pancreas. We performed mutational and immunohistochemical analyses of 4 major genes—KRAS, TP53, CDKN2A, and SMAD4—associated with pancreatic ductal adenocarcinoma progression, as well as targeted next-generation sequencing. Results Mutations in the four genes in the second high-risk lesion were consistent with the first lesion in four patients but were inconsistent in the remaining eight patients, and thus we considered that the latter eight patients likely had metachronous multifocal high-risk lesions and the other four patients had local recurrence. The estimated cumulative recurrence rate after resection of the second high-risk lesion was greater in the local recurrence group compared with the metachronous multifocal group, and the estimated cumulative disease-specific survival rate was greater in the metachronous multifocal group. Targeted next-generation sequencing demonstrated that the second lesions in the metachronous multifocal high-risk lesion group showed differences in founder mutations compared with the first lesion. In the local recurrence group, the founder mutations in the second lesion were common with those in the first lesion. Conclusion Genetic assessment might help discriminate metachronous multifocal high-risk lesions from local recurrence. |
| Databáze: | OpenAIRE |
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