Pathogenesis of multiple pancreatic cancers involves multicentric carcinogenesis and intrapancreatic metastasis
| العنوان: | Pathogenesis of multiple pancreatic cancers involves multicentric carcinogenesis and intrapancreatic metastasis |
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| المؤلفون: | Takashi Tokino, Hiroshi Yagi, Yohei Masugi, Michiie Sakamoto, Yusuke Fujita, Yuta Abe, Yasushi Sasaki, Yuko Kitagawa, Masahiro Shinoda, Minoru Kitago, Sachiko Matsuda |
| المصدر: | Cancer Science |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cancer Research, endocrine system diseases, DNA Mutational Analysis, Pancreatic Intraepithelial Neoplasia, next‐generation sequence, medicine.disease_cause, Metastasis, Pathogenesis, Neoplasms, Multiple Primary, 0302 clinical medicine, multicentric occurrence, pancreatic intraepithelial neoplasia, Pathology, multiple pancreatic cancers, Smad4 Protein, pancreatic carcinogenesis, Mutation, High-Throughput Nucleotide Sequencing, Neoplasms, Second Primary, General Medicine, Oncology, 030220 oncology & carcinogenesis, Immunohistochemistry, Female, Original Article, Carcinoma, Pancreatic Ductal, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Pancreatectomy, Cell Line, Tumor, medicine, Biomarkers, Tumor, Humans, Pathological, Neoplasm Staging, business.industry, Cancer, Sequence Analysis, DNA, Original Articles, medicine.disease, Survival Analysis, digestive system diseases, Pancreatic Neoplasms, 030104 developmental biology, Cancer research, Tumor Suppressor Protein p53, business, Immunostaining |
| الوصف: | There are increased opportunities in oncology clinics to identify multiple pancreatic ductal adenocarcinomas (PDAC) that co‐occur simultaneously or arise metachronously in the pancreatic parenchyma, yet their pathogenesis remains elusive. We hypothesized that two potential pathways, multicentric carcinogenesis and intrapancreatic metastasis, might contribute to forming multiple PDAC. Among 241 resected cases, we identified 20 cancer nodules from nine patients with multiple PDAC (six with synchronous PDAC, one with metachronous PDAC, and two with both synchronous and metachronous PDAC). Integrated clinical, pathological, and mutational analyses, using TP53 and SMAD4 immunostaining and targeted next‐generation sequencing of 50 cancer‐related genes, were conducted to examine the intertumor relationships. Four of the nine patients were assessed as having undergone multicentric carcinogenesis because of heterogeneity of immunohistochemical and/or mutation characteristics. In contrast, tumors in the other five patients showed intertumor molecular relatedness. Two of these five patients, available for matched sequencing data, showed two or more shared mutations. Moreover, all the smaller nodules in these five patients showed identical TP53 and SMAD4 expression patterns to the corresponding main tumors. Consequently, these five patients were considered to have undergone intrapancreatic metastasis. None of the five smaller nodules arising from intrapancreatic metastasis was accompanied by pancreatic intraepithelial neoplasia, and three of them were tiny (≤1mm). Patients whose tumors resulted from intrapancreatic metastasis appeared to have higher disease stages and worse outcome than those with tumors from multicentric carcinogenesis. Our results provide insight into pancreatic carcinogenesis, showing that the development of multiple PDAC involves distinct evolutionary paths that potentially affect patient prognosis. Integrated clinical, pathological, and mutational analyses on multiple pancreatic cancers identify distinct evolutionary paths: multicentric carcinogenesis and intrapancreatic metastasis. |
| تدمد: | 1349-7006 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc62b14be863662219786f44d691d68eTest https://pubmed.ncbi.nlm.nih.gov/31799787Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fc62b14be863662219786f44d691d68e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13497006 |
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