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Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Pancreatic Cancer | Research article

Pancreatic cancer stem cells may define tumor stroma characteristics and recurrence patterns in pancreatic ductal adenocarcinoma

Authors: Gokce Askan, Ibrahim Halil. Sahin, Joanne F. Chou, Aslihan Yavas, Marinela Capanu, Christine A. Iacobuzio-Donahue, Olca Basturk, Eileen M. O’Reilly

Published in: BMC Cancer | Issue 1/2021

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Abstract

Background

Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients.

Methods

PDAC patients who underwent surgical resection between 01/2012–06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher’s exact test.

Results

N = 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44−/ESA+ (35%), CD44−/ESA (9%) (p = 0.0033). Conversely, lack of CD44 and ESA expression was associated with the highest rate of moderate and dense stroma (91% p = 0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence was observed in patients with loose stroma. No statistically significant difference in RFS and OS was observed among subgroups (P = 0.089).

Conclusions

These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Our results further suggest that tumor stroma may influence the recurrence pattern in PDAC patients.
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Literature
7.
go back to reference Sahin I, Askan G, Hu Z, O’Reilly E. Immunotherapy in Pancreatic Ductal Adenocarcinoma: An Emerging Entity? Ann Oncol. 2017;28:mdx503.CrossRef Sahin I, Askan G, Hu Z, O’Reilly E. Immunotherapy in Pancreatic Ductal Adenocarcinoma: An Emerging Entity? Ann Oncol. 2017;28:mdx503.CrossRef
13.
go back to reference Lowery MA, Kelsen DP, Stadler ZK, Kenneth HY, Janjigian YY, Ludwig E, et al. An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions. Oncologist. 2011;16(10):1397–402. https://doi.org/10.1634/theoncologist.2011-0185. Lowery MA, Kelsen DP, Stadler ZK, Kenneth HY, Janjigian YY, Ludwig E, et al. An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions. Oncologist. 2011;16(10):1397–402. https://​doi.​org/​10.​1634/​theoncologist.​2011-0185.
14.
17.
go back to reference Catenacci DV, Junttila MR, Karrison T, Bahary N, Horiba MN, Nattam SR, et al. Randomized phase Ib/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer. J Clin Oncol. 2015;33(36):4284–92. https://doi.org/10.1200/JCO.2015.62.8719. Catenacci DV, Junttila MR, Karrison T, Bahary N, Horiba MN, Nattam SR, et al. Randomized phase Ib/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer. J Clin Oncol. 2015;33(36):4284–92. https://​doi.​org/​10.​1200/​JCO.​2015.​62.​8719.
18.
go back to reference Ramanathan RK, McDonough SL, Philip PA, Hingorani SR, Lacy J, Kortmansky JS, et al. Phase IB/II randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313. J Clin Oncol. 2019;37(13):1062–9. https://doi.org/10.1200/JCO.18.01295. Ramanathan RK, McDonough SL, Philip PA, Hingorani SR, Lacy J, Kortmansky JS, et al. Phase IB/II randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313. J Clin Oncol. 2019;37(13):1062–9. https://​doi.​org/​10.​1200/​JCO.​18.​01295.
19.
go back to reference Tempero MA, Van Cutsem E, Sigal D, Oh D-Y, Fazio N, Macarulla T, et al. HALO 109–301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20)+ nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA). Am Soc Clin Oncol. 2020;38(4):638. Tempero MA, Van Cutsem E, Sigal D, Oh D-Y, Fazio N, Macarulla T, et al. HALO 109–301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20)+ nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA). Am Soc Clin Oncol. 2020;38(4):638.
20.
go back to reference Sahin IH. Precision medicine for gastrointestinal cancers: a conference report: Future Science; 2020. Sahin IH. Precision medicine for gastrointestinal cancers: a conference report: Future Science; 2020.
22.
go back to reference Hyun K-A, Koo G-B, Han H, Sohn J, Choi W, Kim S-I, et al. Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer. Oncotarget. 2016;7(17):24677–87. https://doi.org/10.18632/oncotarget.8250. Hyun K-A, Koo G-B, Han H, Sohn J, Choi W, Kim S-I, et al. Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer. Oncotarget. 2016;7(17):24677–87. https://​doi.​org/​10.​18632/​oncotarget.​8250.
24.
go back to reference Oguzsoy T, Bagci P, Akbas G. Immunohistochemical staining patterns of the PDAC stroma and their prognostic implications. In: VIRCHOWS ARCHIV. New York: Springer; 2018. p. S8. Oguzsoy T, Bagci P, Akbas G. Immunohistochemical staining patterns of the PDAC stroma and their prognostic implications. In: VIRCHOWS ARCHIV. New York: Springer; 2018. p. S8.
32.
go back to reference Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105.CrossRefPubMed Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105.CrossRefPubMed
33.
go back to reference Clarke MF, Hass AT. Cancer stem cells. Rev Cell Biol Mol Med. 2006:9339–44. Clarke MF, Hass AT. Cancer stem cells. Rev Cell Biol Mol Med. 2006:9339–44.
36.
go back to reference Madden J. Infinity reports update from phase 2 study of saridegib plus gemcitabine in patients with metastatic pancreatic cancer. Infinity Pharm. 2012:1. Madden J. Infinity reports update from phase 2 study of saridegib plus gemcitabine in patients with metastatic pancreatic cancer. Infinity Pharm. 2012:1.
Metadata
Title
Pancreatic cancer stem cells may define tumor stroma characteristics and recurrence patterns in pancreatic ductal adenocarcinoma
Authors
Gokce Askan
Ibrahim Halil. Sahin
Joanne F. Chou
Aslihan Yavas
Marinela Capanu
Christine A. Iacobuzio-Donahue
Olca Basturk
Eileen M. O’Reilly
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-08123-w

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