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Generation and characterization of a cell line from an intraductal tubulopapillary neoplasm of the pancreas.

ABSTRACT: Intraductal tubulopapillary neoplasm (ITPN) is a distinct precancerous lesion in the pancreas with unique clinical and molecular features. Although in vitro studies in two-dimensional culture have led to numerous important insights in pancreatic cancer, such models are currently lacking for precancerous lesions. In this study, we report the generation and characterization of a cell line from a human pancreatic ITPN. Neoplastic cells were initially cultured in a three-dimensional organoid system, followed by transfer to two-dimensional culture. RNA sequencing revealed a gene expression profile consistent with pancreatic ductal origin, and whole genome sequencing identified many somatic mutations (including in genes involved in DNA repair and Wnt signaling) and structural rearrangements. In vitro characterization of the tumorigenic potential demonstrated a phenotype between that of normal pancreatic ductal cells and cancer cell lines. This cell line represents a valuable resource for interrogation of unique ITPN biology, as well as precancerous pancreatic lesions more generally.

SUBMITTER: Felsenstein M

PROVIDER: S-EPMC7316603 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Generation and characterization of a cell line from an intraductal tubulopapillary neoplasm of the pancreas.

Felsenstein Matthäus M Trujillo Maria A MA Huang Bo B Nanda Neha N Jiang Zhengdong Z Jeong Yea Ji YJ Pflüger Michael M Goggins Michael G MG Hruban Ralph H RH Thompson Elizabeth D ED Heaphy Christopher M CM Roberts Nicholas J NJ Wood Laura D LD

Laboratory investigation; a journal of technical methods and pathology 20200131 7

Intraductal tubulopapillary neoplasm (ITPN) is a distinct precancerous lesion in the pancreas with unique clinical and molecular features. Although in vitro studies in two-dimensional culture have led to numerous important insights in pancreatic cancer, such models are currently lacking for precancerous lesions. In this study, we report the generation and characterization of a cell line from a human pancreatic ITPN. Neoplastic cells were initially cultured in a three-dimensional organoid system, ...[more]

PMID: 32005909

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Project description:Intraductal tubulopapillary neoplasm (ITPN) is a relatively recently described member of the pancreatic intraductal neoplasm family. Thus, the literature on its histologic and immunohistochemical features, clinical behavior, and its similarities and differences from other pancreatic neoplasms is limited. Thirty-three cases of ITPN, the largest series to date, were identified. Immunohistochemical labeling for cytokeratins, glycoproteins, pancreatic enzymes, markers for intestinal and neuroendocrine differentiation, and antibodies associated with genetic alterations previously described in pancreatic neoplasms was performed. Clinicopathologic features and survival was assessed. Seventeen patients were female and 14 were male. Mean age was 55 years (range, 25 to 79 y). Median overall tumor size was 4.5 cm (range, 0.5 to 15 cm). Forty-five percent of the tumors occurred in the head, 32% in the body/tail, and 23% showed diffuse involvement. Microscopically, the tumors were characterized by intraductal nodules composed of tightly packed small tubular glands lined by cuboidal cells lacking apparent mucin. Although it was often challenging to determine its extent, invasion was present in 71%. Almost all tumors labeled for CAM5.2, CK7, and CK19; most expressed CA19.9, MUC1, and MUC6. CDX2, MUC2, trypsin, chymotrypsin, chromogranin, and synaptophysin were not expressed. SMAD4 expression was retained in 100%; p16 expression and p53 overexpression was seen in 33% and 27%, respectively. Follow-up information was available for 22 patients (median follow-up, 45 mo; range, 11 to 173 mo). Two patients with invasive carcinoma died of disease at 23 and 41 months, respectively. One patient died of unrelated causes at 49 months. Twelve patients were alive with disease. Seven patients were alive with no evidence of disease. The overall 1-, 3-, and 5-year survival rates were 100% in patients without an invasive component and 100%, 91%, and 71%, respectively, in patients with an invasive component (P=0.7). ITPN is a distinct clinicopathologic entity in the pancreas. Despite the difficulties of determining the extent of invasive carcinoma in many cases, the overall outcome seems to be relatively favorable and substantially better than that of conventional pancreatic ductal adenocarcinoma, even when only the cases with invasive carcinoma are considered.

Dataset Information

Generation and characterization of a cell line from an intraductal tubulopapillary neoplasm of the pancreas.

Publications

Generation and characterization of a cell line from an intraductal tubulopapillary neoplasm of the pancreas.

Similar Datasets

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