Histomorphology of pancreatic cancer in patients with inherited ATM serine/threonine kinase pathogenic variants

Danielle Hutchings, Zhengdong Jiang, Michael Skaro, Matthew J Weiss, Christopher Wolfgang, Martin A Makary, Jin He, John L Cameron, Lei Zheng, David S. Klimstra, Randall E. Brand, Aatur D. Singhi, Michael S Goggins, Alison Klein, Nicholas Roberts, Ralph H Hruban

Research output: Contribution to journalArticle

Abstract

Germline pathogenic variants in the ATM serine/threonine kinase (ATM) gene are associated with an increased risk of pancreatic ductal adenocarcinoma. It is important to identify germline ATM pathogenic variants in pancreatic cancer patients because these alterations are potentially targetable with chemotherapeutic drugs and/or radiation and have implications for other family members. As germline pathogenic variants in other genes have been associated with distinct histologic subtypes of pancreatic cancer, we studied the histomorphology of pancreatic cancer in 23 patients with germline ATM pathogenic variants. The histologic subtype was ductal adenocarcinoma in 19/23 (83%) of the patients, adenosquamous carcinoma in 1/23 (4%), and colloid (mucinous non-cystic) carcinoma in 3/23 (13%). The percentage of colloid (mucinous non-cystic) carcinomas is higher than we have previously observed in patients with familial and sporadic pancreatic cancer (1 and 2% in prior reports, p < 0.01 and p < 0.01, respectively). Three carcinomas (2 colloid carcinomas, 1 ductal adenocarcinoma) arose in association with intraductal papillary mucinous neoplasms. Among the resected pancreata, non-invasive precursor lesions, including pancreatic intraepithelial neoplasia and incipient intraductal papillary mucinous neoplasms, were identified in 83%. We conclude that pancreatic cancers in patients with germline ATM pathogenic variants are more frequently of colloid (mucinous non-cystic) morphology but are overall morphologically diverse supporting the utility of universal germline genetic testing for patients with pancreatic cancer.

Original languageEnglish (US)
JournalModern Pathology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Protein-Serine-Threonine Kinases
Pancreatic Neoplasms
Colloids
Adenocarcinoma
Carcinoma
Adenosquamous Carcinoma
Mucinous Adenocarcinoma
Neoplasms
Genetic Testing
Genes
Pancreas
Radiation
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{f51f955a1e0e416e80446cb9f92c1590,
title = "Histomorphology of pancreatic cancer in patients with inherited ATM serine/threonine kinase pathogenic variants",
abstract = "Germline pathogenic variants in the ATM serine/threonine kinase (ATM) gene are associated with an increased risk of pancreatic ductal adenocarcinoma. It is important to identify germline ATM pathogenic variants in pancreatic cancer patients because these alterations are potentially targetable with chemotherapeutic drugs and/or radiation and have implications for other family members. As germline pathogenic variants in other genes have been associated with distinct histologic subtypes of pancreatic cancer, we studied the histomorphology of pancreatic cancer in 23 patients with germline ATM pathogenic variants. The histologic subtype was ductal adenocarcinoma in 19/23 (83{\%}) of the patients, adenosquamous carcinoma in 1/23 (4{\%}), and colloid (mucinous non-cystic) carcinoma in 3/23 (13{\%}). The percentage of colloid (mucinous non-cystic) carcinomas is higher than we have previously observed in patients with familial and sporadic pancreatic cancer (1 and 2{\%} in prior reports, p < 0.01 and p < 0.01, respectively). Three carcinomas (2 colloid carcinomas, 1 ductal adenocarcinoma) arose in association with intraductal papillary mucinous neoplasms. Among the resected pancreata, non-invasive precursor lesions, including pancreatic intraepithelial neoplasia and incipient intraductal papillary mucinous neoplasms, were identified in 83{\%}. We conclude that pancreatic cancers in patients with germline ATM pathogenic variants are more frequently of colloid (mucinous non-cystic) morphology but are overall morphologically diverse supporting the utility of universal germline genetic testing for patients with pancreatic cancer.",
author = "Danielle Hutchings and Zhengdong Jiang and Michael Skaro and Weiss, {Matthew J} and Christopher Wolfgang and Makary, {Martin A} and Jin He and Cameron, {John L} and Lei Zheng and Klimstra, {David S.} and Brand, {Randall E.} and Singhi, {Aatur D.} and Goggins, {Michael S} and Alison Klein and Nicholas Roberts and Hruban, {Ralph H}",
year = "2019",
month = "1",
day = "1",
doi = "10.1038/s41379-019-0317-6",
language = "English (US)",
journal = "Modern Pathology",
issn = "0893-3952",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Histomorphology of pancreatic cancer in patients with inherited ATM serine/threonine kinase pathogenic variants

AU - Hutchings, Danielle

AU - Jiang, Zhengdong

AU - Skaro, Michael

AU - Weiss, Matthew J

AU - Wolfgang, Christopher

AU - Makary, Martin A

AU - He, Jin

AU - Cameron, John L

AU - Zheng, Lei

AU - Klimstra, David S.

AU - Brand, Randall E.

AU - Singhi, Aatur D.

AU - Goggins, Michael S

AU - Klein, Alison

AU - Roberts, Nicholas

AU - Hruban, Ralph H

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Germline pathogenic variants in the ATM serine/threonine kinase (ATM) gene are associated with an increased risk of pancreatic ductal adenocarcinoma. It is important to identify germline ATM pathogenic variants in pancreatic cancer patients because these alterations are potentially targetable with chemotherapeutic drugs and/or radiation and have implications for other family members. As germline pathogenic variants in other genes have been associated with distinct histologic subtypes of pancreatic cancer, we studied the histomorphology of pancreatic cancer in 23 patients with germline ATM pathogenic variants. The histologic subtype was ductal adenocarcinoma in 19/23 (83%) of the patients, adenosquamous carcinoma in 1/23 (4%), and colloid (mucinous non-cystic) carcinoma in 3/23 (13%). The percentage of colloid (mucinous non-cystic) carcinomas is higher than we have previously observed in patients with familial and sporadic pancreatic cancer (1 and 2% in prior reports, p < 0.01 and p < 0.01, respectively). Three carcinomas (2 colloid carcinomas, 1 ductal adenocarcinoma) arose in association with intraductal papillary mucinous neoplasms. Among the resected pancreata, non-invasive precursor lesions, including pancreatic intraepithelial neoplasia and incipient intraductal papillary mucinous neoplasms, were identified in 83%. We conclude that pancreatic cancers in patients with germline ATM pathogenic variants are more frequently of colloid (mucinous non-cystic) morphology but are overall morphologically diverse supporting the utility of universal germline genetic testing for patients with pancreatic cancer.

AB - Germline pathogenic variants in the ATM serine/threonine kinase (ATM) gene are associated with an increased risk of pancreatic ductal adenocarcinoma. It is important to identify germline ATM pathogenic variants in pancreatic cancer patients because these alterations are potentially targetable with chemotherapeutic drugs and/or radiation and have implications for other family members. As germline pathogenic variants in other genes have been associated with distinct histologic subtypes of pancreatic cancer, we studied the histomorphology of pancreatic cancer in 23 patients with germline ATM pathogenic variants. The histologic subtype was ductal adenocarcinoma in 19/23 (83%) of the patients, adenosquamous carcinoma in 1/23 (4%), and colloid (mucinous non-cystic) carcinoma in 3/23 (13%). The percentage of colloid (mucinous non-cystic) carcinomas is higher than we have previously observed in patients with familial and sporadic pancreatic cancer (1 and 2% in prior reports, p < 0.01 and p < 0.01, respectively). Three carcinomas (2 colloid carcinomas, 1 ductal adenocarcinoma) arose in association with intraductal papillary mucinous neoplasms. Among the resected pancreata, non-invasive precursor lesions, including pancreatic intraepithelial neoplasia and incipient intraductal papillary mucinous neoplasms, were identified in 83%. We conclude that pancreatic cancers in patients with germline ATM pathogenic variants are more frequently of colloid (mucinous non-cystic) morphology but are overall morphologically diverse supporting the utility of universal germline genetic testing for patients with pancreatic cancer.

UR - http://www.scopus.com/inward/record.url?scp=85068937744&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068937744&partnerID=8YFLogxK

U2 - 10.1038/s41379-019-0317-6

DO - 10.1038/s41379-019-0317-6

M3 - Article

C2 - 31285527

AN - SCOPUS:85068937744

JO - Modern Pathology

JF - Modern Pathology

SN - 0893-3952

ER -