Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun;58(6):575-585.
doi: 10.1007/s00535-023-01986-9. Epub 2023 Apr 7.

Genomic landscape and clinical features of rare subtypes of pancreatic cancer: analysis with the national database of Japan

Tomoki Sakakida  1   2 , Takeshi Ishikawa  3   4   5 , Toshifumi Doi  1   2 , Ryuichi Morita  1   2 , Seita Kataoka  1 , Hayato Miyake  1 , Kanji Yamaguchi  1 , Michihisa Moriguchi  1 , Yoshio Sogame  1 , Hiroaki Yasuda  1 , Masahiro Iwasaku  2 , Hideyuki Konishi  1 , Koichi Takayama  2   6 , Yoshito Itoh  1
Affiliations

Genomic landscape and clinical features of rare subtypes of pancreatic cancer: analysis with the national database of Japan

Tomoki Sakakida et al. J Gastroenterol. 2023 Jun.

Abstract

Background: Special subtypes of pancreatic cancer, such as acinar cell carcinoma (ACC), adenosquamous carcinoma (ASC), and anaplastic carcinoma of the pancreas (ACP), are rare, and so data on them are limited. Using the C-CAT database, we analyzed clinical and genomic characteristics of patients with these and evaluated differences on comparison with pancreatic ductal adenocarcinoma (PDAC) patients.

Methods: We retrospectively reviewed data on 2691 patients with unresectable pancreatic cancer: ACC, ASC, ACP, and PDAC, entered into C-CAT from June 2019 to December 2021. The clinical features, MSI/TMB status, genomic alterations, overall response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) on receiving FOLFIRINOX (FFX) or GEM + nab-PTX (GnP) therapy as first-line treatment were evaluated.

Results: Numbers of patients with ACC, ASC, ACP, and PDAC were 44 (1.6%), 54 (2.0%), 25 (0.9%), and 2,568 (95.4%), respectively. KRAS and TP53 mutations were prevalent in ASC, ACP, and PDAC (90.7/85.2, 76.0/68.0, and 85.1/69.1%, respectively), while their rates were both significantly lower in ACC (13.6/15.9%, respectively). Conversely, the rate of homologous recombination-related (HRR) genes, including ATM and BRCA1/2, was significantly higher in ACC (11.4/15.9%) than PDAC (2.5/3.7%). In ASC and ACP, no significant differences in ORR, DCR, or TTF between FFX and GnP were noted, while ACC patients showed a trend toward higher ORR with FFX than GnP (61.5 vs. 23.5%, p = 0.06) and significantly more favorable TTF (median 42.3 vs. 21.0 weeks, respectively, p = 0.004).

Conclusions: ACC clearly harbors different genomics compared with PDAC, possibly accounting for differences in treatment efficacy.

Keywords: Acinar cell carcinoma; Adenosquamous carcinoma; Anaplastic carcinoma of the pancreas; Genome analysis; Pancreatic ductal adenocarcinoma.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow diagram of the study. The diagram displays the tumor types which were excluded and the number of cases of acinar cell carcinoma (ACC), adenosquamous carcinoma (ASC), anaplastic carcinoma of the pancreas (ACP), and pancreatic ductal adenocarcinoma (PDAC), respectively
Fig. 2
Fig. 2
Overview of the most common genomic alterations. Data are shown for a acinar cell carcinoma (ACC), b adenosquamous carcinoma (ASC), c anaplastic carcinoma of the pancreas (ACP), and d pancreatic ductal adenocarcinoma (PDAC). The genes most frequently found in PDAC are listed from the top to bottom
Fig. 3
Fig. 3
The frequency of major genomic alterations among rare subtypes of pancreatic cancer and pancreatic ductal adenocarcinoma (PDAC). Data are shown for a top 4 and b 5th-10th gene mutations found in PDAC. c shows the distribution of KRAS subtypes, d and e show the frequencies of the representative homologous recombination repair (HRR) and mismatch repair (MMR) genes among the four tumor types, respectively
Fig. 4
Fig. 4
MSI and TMB status among rare subtypes of pancreatic cancer and pancreatic ductal adenocarcinoma (PDAC). The distribution of a MSI status, b TMB status and c TMB load among the four tumor types are shown
Fig. 5
Fig. 5
Kaplan–Meier curves of time to treatment failure (TTF) according to first-line FOLFIRINOX (FFX) versus gemcitabine plus nab-paclitaxel (GnP) therapy. Data are shown for a pancreatic ductal adenocarcinoma (PDAC), b acinar cell carcinoma (ACC), c adenosquamous carcinoma (ASC), and d anaplastic carcinoma of pancreas (ACP) patients
See this image and copyright information in PMC

Comment in

References

    1. Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol. 2019;10:10–27. doi: 10.14740/wjon1166. - DOI - PMC - PubMed
    1. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin. 2021;71:7–33. doi: 10.3322/caac.21654. - DOI - PubMed
    1. Vincent A, Herman J, Schulick R, et al. Pancreatic cancer. Lancet. 2011;378:607–620. doi: 10.1016/S0140-6736(10)62307-0. - DOI - PMC - PubMed
    1. Matsuno S, Egawa S, Fukuyama S, et al. Pancreatic Cancer Registry in Japan: 20 years of experience. Pancreas. 2004;28:219–230. doi: 10.1097/00006676-200404000-00002. - DOI - PubMed
    1. Schmidt CM, Matos JM, Bentrem DJ, et al. Acinar cell carcinoma of the pancreas in the United States: prognostic factors and comparison to ductal adenocarcinoma. J Gastrointest Surg. 2008;12:2078–2086. doi: 10.1007/s11605-008-0705-6. - DOI - PubMed

MeSH terms