TY - JOUR
T1 - Pulmonary adenocarcinoma with signet ring cell features
T2 - A Comprehensive study from 3 distinct patient cohorts
AU - Boland, Jennifer M.
AU - Wampfler, Jason A.
AU - Jang, Jin S.
AU - Wang, Xiaoke
AU - Erickson-Johnson, Michele R.
AU - Oliveira, Andre M.
AU - Yang, Ping
AU - Jen, Jin
AU - Yi, Eunhee S.
N1 - Publisher Copyright:
Copyright © 2014 by Lippincott Williams & Wilkins.
PY - 2014
Y1 - 2014
N2 - Comprehensive biological characteristics of pulmonary adenocarcinomas with signet ring cell features (SRC+) are not well known. Herein, we systematically evaluated clinical and molecular features of SRC+ cases with particular attention to smoking status. Surgically treated lung adenocarcinomas (n=763) with follow-up ≥5 years in 3 cohorts were reviewed: all patients in 2006 to 2007 ("all-comers," n=222; 168 eversmokers), a never-smoker cohort (n=266), and a cohort of ever-smokers (n=275). SRC+ tumors had ≥10% of SRCs agreed by 2 pathologists. SRC+ cases were tested for rearrangement of ALK and ROS1, as well as 187 known mutations in 10 oncogenes including EGFR, KRAS, BRAF, ERBB2, JAK2, AKT1, AKT2, KIT, MET, and PIK3CA. Overall, 53 of 763 cases (7%) were SRC+. In the 2006 to 2007 "all comer" cohort, 9% were SRC+. In the never-smoker cohort, 9% were SRC+. In the smoker cohort, 3% were SRC+. Univariable analysis showed that SRC+ never-smokers had shorter overall and disease-free survival (P=0.006 and 0.0004, respectively), but the significance faded in the multivariable analysis. For the other 2 cohorts, crude 5-year survival was decreased by 6% to 27% in SRC+ cases without reaching statistical significance. In SRC+ tumors, KRAS mutation was most common (29%), followed by ALK (26%), EGFR (18%), ROS1 (6%), BRAF (6%), and PIK3CA (3%). In summary, SRC+ tumors in neversmokers had a worse survival by univariable analysis only. SRC+ cases seemed enriched for ALK+ and ROS1+, and other mutations were generally in keeping with the patient's smoking status.
AB - Comprehensive biological characteristics of pulmonary adenocarcinomas with signet ring cell features (SRC+) are not well known. Herein, we systematically evaluated clinical and molecular features of SRC+ cases with particular attention to smoking status. Surgically treated lung adenocarcinomas (n=763) with follow-up ≥5 years in 3 cohorts were reviewed: all patients in 2006 to 2007 ("all-comers," n=222; 168 eversmokers), a never-smoker cohort (n=266), and a cohort of ever-smokers (n=275). SRC+ tumors had ≥10% of SRCs agreed by 2 pathologists. SRC+ cases were tested for rearrangement of ALK and ROS1, as well as 187 known mutations in 10 oncogenes including EGFR, KRAS, BRAF, ERBB2, JAK2, AKT1, AKT2, KIT, MET, and PIK3CA. Overall, 53 of 763 cases (7%) were SRC+. In the 2006 to 2007 "all comer" cohort, 9% were SRC+. In the never-smoker cohort, 9% were SRC+. In the smoker cohort, 3% were SRC+. Univariable analysis showed that SRC+ never-smokers had shorter overall and disease-free survival (P=0.006 and 0.0004, respectively), but the significance faded in the multivariable analysis. For the other 2 cohorts, crude 5-year survival was decreased by 6% to 27% in SRC+ cases without reaching statistical significance. In SRC+ tumors, KRAS mutation was most common (29%), followed by ALK (26%), EGFR (18%), ROS1 (6%), BRAF (6%), and PIK3CA (3%). In summary, SRC+ tumors in neversmokers had a worse survival by univariable analysis only. SRC+ cases seemed enriched for ALK+ and ROS1+, and other mutations were generally in keeping with the patient's smoking status.
KW - ALK
KW - Adenocarcinoma
KW - Lung
KW - Mutations
KW - ROS1
KW - Signet ring cell
KW - Smoking status
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=84914677993&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84914677993&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000000280
DO - 10.1097/PAS.0000000000000280
M3 - Article
C2 - 25007143
AN - SCOPUS:84914677993
SN - 0147-5185
VL - 38
SP - 1681
EP - 1688
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 12
ER -