Plasma carcinoembryonic antigen and acinar cell carcinoma of the pancreas

Horie, Yutaka; Gomyoda, Manabu; Kishimoto, Yukihiro; Ueki, Juichi; F, Ikeda; Murawaki, Yoshikazu; Kawamura, Manabu; Hirayama, Chisato

doi:10.1002/1097-0142(19840301)53:5<1137::aid-cncr2820530520>3.0.co;2-7

Cited by 14 publications

(6 citation statements)

References 11 publications

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“…Our in vivo model of human PACC can provide a novel means to further investigate the genetic and cellular mechanisms of this disease. Hence, we confirmed that the PDTX tumors were composed of human acinar cell carcinoma cells via STR profile, corroboration of biomarker expression seen in PACC patient tissues [ 15 – 18 ] and secretion of lipase into the bloodstream [ 14 , 48 ] (Additional file 1 : Table S1; Figs. 1 , 3 ).…”

Section: Discussionsupporting

confidence: 76%

“…1 c, panels i–iii). PA-018 also expressed previously documented markers of PACC, including CEA [ 15 ], CK18 [ 16 ] and BCL10 [ 17 , 18 ] (Fig. 1 c, panels iv, vi) and had a lack of cytokeratin 19 (CK19) expression, a marker of ducts and pancreatic ductal tumors [ 23 ] (Fig.…”

Section: Resultsmentioning

confidence: 72%

“…However, elevated serum lipase and amylase levels can be seen in both PACC and acute pancreatitis leading to difficulties in establishing a correct diagnosis [ 13 , 14 ]. Reliable markers of PACC have been slowly emerging such as carcinoembryonic antigen (CEA) [ 15 ], cytokeratin 18 (CK18) [ 16 ] and B-cell lymphoma/leukemia 10 (BCL10) [ 17 , 18 ] allowing us to distinguish acinar cell carcinoma from normal acinar cells or other pancreatic cancers through histology.…”

Section: Introductionmentioning

confidence: 99%

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Novel patient-derived xenograft mouse model for pancreatic acinar cell carcinoma demonstrates single agent activity of oxaliplatin

Hall

Marlow

Mathias³

et al. 2016

J Transl Med

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BackgroundPancreatic acinar cell carcinoma (PACC) is a rare malignancy, accounting for <1 % of all pancreatic neoplasms. Very few retrospective studies are available to help guide management. We previously reported the case of a patient with metastatic PACC who achieved prolonged survival following doxorubicin treatment. Personalized treatment was based on molecular and in vitro data collected from primary cells developed from their liver metastasis. We now report the characterization of a patient derived tumor xenograft (PDTX) mouse model that originated from this patient’s PACC liver metastasis.MethodsFragments of biopsy tissue (5 mm3) from PACC liver metastasis were implanted into athymic nude mice. Tumors were grown and passaged from the host mice into new mice to be tested for therapeutic response. Immuno-histochemical (IHC) biomarkers were used to confirm that the PDTX model represents human PACC. The antitumor activities of multiple drugs (5-FU, irinotecan, oxaliplatin, gemcitabine, bevacizumab, erlotinib, doxorubicin and imatinib) were tested. Tumor size was measured over 74 days or until they reached an endpoint volume of ~800 mm3. Tests to measure serum lipase levels and histological analyses of tumor tissues were also conducted to assess PACC progression and re-differentiation.ResultsThe model presented here expresses the same IHC markers found in human PACC. In the chemotherapy study, oxaliplatin produced a prolonged durable growth response associated with increased apoptosis, decreased serum lipase levels and increased healthy acinar cells. Bevacizumab also produced a significant growth response, but the effect was not prolonged as demonstrated by oxaliplatin treatment. The other chemotherapies had moderate to little effect, particularly after treatment ceased. Mutations in DNA repair genes are common in PACC and increase tumor susceptibility to oxaliplatin. To explore this we performed IHC and found no nuclear expression of BRCA2 in our model, indicating a mutation affecting nuclear localization. Gene sequencing confirms BRCA2 has a homozygous gene deletion on Exon 10, which frequently causes a protein truncation.ConclusionsIn summary, we report the development and characterization of the first and only preclinical PACC PDTX model. Here we show sustained anti-tumor activity of single agent oxaliplatin, a compound that is more effective in tumors that harbor mutations in DNA repair genes. Our data shows that BRCA2 is mutated in our PACC model, which could contribute to the oxaliplatin sensitivity observed. Further studies on this rare PACC model can serve to elucidate other novel therapies, biomarkers, and molecular mechanisms of signaling and drug resistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0875-z) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 76%

Section: Resultsmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Novel patient-derived xenograft mouse model for pancreatic acinar cell carcinoma demonstrates single agent activity of oxaliplatin

Hall

Marlow

Mathias³

et al. 2016

J Transl Med

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“…Patients usually present only non-specific symptoms (Klimstra et al 1992), but in some cases, lipase produced by the tumour cells may cause arthralgia and subcutaneous fat necrosis (Robertson & Eeles 1970;Burns et al 1974;Radin et al 1986). Analysis of common tumour markers in serum usually gives negative results (Klimstra et al 1992), but elevated concentrations of alpha-fetoprotein (Le Borgne et al 1989;Ztoh et al 1992;Kawamoto et al 1992;Nojima et al 1992) and carcinoembryonic antigen have occasionally been reported (Horie et al 1984). Elevated concentration of elastase-1 has been reported in serum in one case (Zshihara et al 1989).…”

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confidence: 99%

Acinar cell carcinoma of the pancreas

Kuopio

Ekfors

Nikkanen

et al. 1995

APMIS

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TEIJO KUOPI0,I TAUNO 0. EKFORS,' VAINAMO NIKKANEN2 and T I M 0 J. NEVALAINEN' IDepartment of Pathology and 2Department of Radiotherapy and Medical Oncology, University of Turku, Turku. Finland Kuopio, T., Ekfors, T. O., Nikkanen, V. & Nevalainen T. J. Acinar cell carcinoma of the pancreas. Report of three cases. APMIS 103: 69-78, 1995.Pancreatic acinar cell carcinoma is a rare neoplasm (comprising about 1% of pancreatic tumours). We studied three cases (61-year-old female; 42-year-old male; 57-year-old male), whose survival after diagnosis ranged from 1 year 2 months to 6 years 8 months. There were widespread metastases in each case. The tumours had acinar, trabecular and solid growth patterns. By immunohistochemistry, pancreatic acinar cell markers including carboxyl ester lipase, pancreatic secretory trypsin inhibitor and pancreatic phospholipase A2 (group I PLAz) gave a strong positive reaction in all three cases. By electron microscopy, zymogen granules were seen in the cytoplasm of the tumour cells. Immunostaining for prostate-specific antigen was positive in all three cases. Above-normal concentrations of pancreatic PLA2 were measured in the serum of one patient and the values decreased during chemotherapy concomitantly with the reduction in the size of the tumour mass. In conclusion, immunohistochemical demonstration of the secretory products of acinar cells including the new marker pancreatic PLA2 is useful in the differential diagnosis of pancreatic acinar cell carcinoma. Determination of the concentration of pancreatic group I PLA2 in serum may be helpful in the evaluation of therapy.

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“…Immunohistochemical positivity in ACC has been reported mainly for trypsin, but also for chymotrypsin, lipase, α‐1‐antitrypsin, cytokeratin, lysozyme and rarely for amylase [1,2,5,13,14]. In addition, ACC can show positivity for various tumour markers such as alpha‐fetoprotein [15], carcinoembryonic antigen [15,16] and CA 19–9 [15].…”

Section: Discussionmentioning

confidence: 99%