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. 2024 Oct 9;16(19):3421.
doi: 10.3390/cancers16193421.

Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series

Ashwathy Balachandran Pillai  1 , Mahmoud Yousef  2 , Abdelrahman Yousef  2 , Kristin D Alfaro-Munoz  2 , Brandon G Smaglo  2 , Jason Willis  2 , Robert A Wolff  2 , Shubham Pant  2 , Mark W Hurd  2   3 , Anirban Maitra  4   5 , Huamin Wang  4   5 , Matthew Harold G Katz  6 , Laura R Prakash  6 , Ching-Wei D Tzeng  6 , Rebecca Snyder  6 , Luca F Castelnovo  2 , Anthony Chen  2 , Andrey Kravets  7 , Kseniia Kudriavtseva  7 , Artem Tarasov  7 , Kirill Kryukov  7 , Haoqiang Ying  8 , John Paul Shen  2 , Dan Zhao  2
Affiliations

Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series

Ashwathy Balachandran Pillai et al. Cancers (Basel). .

Abstract

Objectives: Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than those of pancreatic ductal adenocarcinoma. Methods: We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022 and two cases from 2023-2024 who underwent RNA and TME analysis by Boston Gene. Patient information was extracted from our institutional database with the approval of the Institutional Review Board. Results: We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, one had borderline resectable disease, and one had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (one patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC.

Keywords: KRAS; OS; acinar cell carcinoma; immunohistochemistry; pancreatic.

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Conflict of interest statement

Brandon G. Smaglo: Consulting for Ipsen. Shubham Pant: Advisor for Zymeworks, Ipsen, Novartis, Janssen, Boehringer Ingelheim, and AskGene Pharma, and he receives research funding from Mirati Therapeutics, Lilly, Xencor, Novartis, Rgenix, Bristol-Myers Squibb, Astellas Pharma, Framewave, 4D Pharma, Boehringer Ingelheim, NGM Biopharmaceuticals, Janssen, Arcus Biosciences, Elicio Therapeutics, Bionte, Ipsen, Zymeworks, Pfizer, ImmunoMET, Imuneering, and Amal Therapeutics. Anirban Maitra: Consultant for Tezcat Biosciences, is listed as an inventor on a patent licensed to Thrive Earlier Detection (an Exact Sciences Company) relevant to early detection of pancreatic cancer. Andrey Kravets: Stock option of BostonGene. John Paul Shen: Grant/Research support/collaboration: Celsius Therapeutics, BostonGene, Caris Life Sciences, Natera, Xilis, Palantir, and Genentech. Consulting/Stock ownership: Engine Biosciences and NaDeNo Nanoscience. Dan Zhao: Research support/clinical trials: hMirati/BMS, CARsgen, TriSalus, and Affini-T. Consulting: Ipsen. Authors Andrey Kravets, Kseniia Kudriavtseva, Artem Tarasov, and Kirill Kryukov were employed by the company BostonGene Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Oncoplot of genomic alterations identified in the study patients. Del, deletion.
Figure 2
Figure 2
Patient with RET-1 fusion gene, primary tumor response to selpercatinib.
Figure 2
Figure 2
Patient with RET-1 fusion gene, primary tumor response to selpercatinib.
Figure 3
Figure 3
(A) Kaplan–Meir curves comparing overall survival of 5-FU-based vs. gemcitabine-based treatment regimens. (B) Kaplan–Meir curves comparing progression-free survival of first-line 5-FU-based vs. gemcitabine-based treatment regimens.
Figure 3
Figure 3
(A) Kaplan–Meir curves comparing overall survival of 5-FU-based vs. gemcitabine-based treatment regimens. (B) Kaplan–Meir curves comparing progression-free survival of first-line 5-FU-based vs. gemcitabine-based treatment regimens.
Figure 4
Figure 4
RNA expression and TME features for the two cases tested by BostonGene. (#17, mixed ACC with adenocarcinoma, found NTRK1 fusion) and #18 (pure ACC). (A) TME features of both cases revealed immune desert type. (B,C) RNA expression signatures and % of cell composition. (D) Relative expression of selected genes (dashed lines for reference ranges of PDAC).
See this image and copyright information in PMC

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