TY - JOUR
T1 - Impact of molecular alterations and targeted therapy in appendiceal adenocarcinomas
AU - Raghav, Kanwal P.S.
AU - Shetty, Aditya V.
AU - Kazmi, Syed M.A.
AU - Zhang, Nianxiang
AU - Morris, Jeffrey
AU - Taggart, Melissa
AU - Fournier, Keith
AU - Royal, Richard
AU - Mansfield, Paul
AU - Eng, Cathy
AU - Wolff, Robert A.
AU - Overman, Michael J.
PY - 2013
Y1 - 2013
N2 - Background. Appendiceal adenocarcinomas (AAs) are rare and this has limited their molecular understanding. The purpose of our study was to characterize the molecular profile of AA and explore the role of targeted therapy against cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR). Patients and Methods. We performed a retrospective review of 607 patients with AA at a single institution. A total of 149 patients underwent molecular testing for at least one of the following: activating mutations in KRAS, BRAF, cKIT, EGFR, or PI3K; protein expression of c-KIT or COX-2; or microsatellite instability (MSI) status by immunohistochemistry. Kaplan-Meier product limit method and log-rank test were used to estimate overall survival (OS) and to determine associations among OS, COX-2 expression, KRAS mutations, and other characteristics. Results. Age, grade, stage, signet ring cells, mucinous histology, and completeness of cytoreduction score correlated with survival outcomes. COX-2 expression, KRAS, PI3K, and BRAF mutations were seen in 61%, 55%, 17%, and 4% of patients, respectively. High MSI was seen in 6% of patients. KRAS mutation was strongly associated with well differentiated or moderately differentiated AA (p.01). COX-2 expression (p.33) and the presence of KRAS mutation (p.91) had no impact on OS. The use of celecoxib in patients whose tumors expressed COX-2 (p.84) and the use of cetuximab or panitumumab in patients with KRAS wild-type tumors (p.83) also had no impact on OS. Conclusion. In this cohort, we demonstrated that COX-2 expression and KRAS mutations were frequently seen in AA, although neither exhibited any prognostic significance. MSI was infrequent in AA. Targeted therapy against COX-2 and EGFR appeared to provide no clinical benefit. Well and moderately differentiated AA were molecularly distinct from poorly differentiated AA.
AB - Background. Appendiceal adenocarcinomas (AAs) are rare and this has limited their molecular understanding. The purpose of our study was to characterize the molecular profile of AA and explore the role of targeted therapy against cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR). Patients and Methods. We performed a retrospective review of 607 patients with AA at a single institution. A total of 149 patients underwent molecular testing for at least one of the following: activating mutations in KRAS, BRAF, cKIT, EGFR, or PI3K; protein expression of c-KIT or COX-2; or microsatellite instability (MSI) status by immunohistochemistry. Kaplan-Meier product limit method and log-rank test were used to estimate overall survival (OS) and to determine associations among OS, COX-2 expression, KRAS mutations, and other characteristics. Results. Age, grade, stage, signet ring cells, mucinous histology, and completeness of cytoreduction score correlated with survival outcomes. COX-2 expression, KRAS, PI3K, and BRAF mutations were seen in 61%, 55%, 17%, and 4% of patients, respectively. High MSI was seen in 6% of patients. KRAS mutation was strongly associated with well differentiated or moderately differentiated AA (p.01). COX-2 expression (p.33) and the presence of KRAS mutation (p.91) had no impact on OS. The use of celecoxib in patients whose tumors expressed COX-2 (p.84) and the use of cetuximab or panitumumab in patients with KRAS wild-type tumors (p.83) also had no impact on OS. Conclusion. In this cohort, we demonstrated that COX-2 expression and KRAS mutations were frequently seen in AA, although neither exhibited any prognostic significance. MSI was infrequent in AA. Targeted therapy against COX-2 and EGFR appeared to provide no clinical benefit. Well and moderately differentiated AA were molecularly distinct from poorly differentiated AA.
KW - Appendix adenocarcinoma
KW - COX-2
KW - Celecoxib
KW - Cetuximab
KW - KRAS
KW - MSI
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UR - http://www.scopus.com/inward/citedby.url?scp=84890095787&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2013-0186
DO - 10.1634/theoncologist.2013-0186
M3 - Article
C2 - 24149137
AN - SCOPUS:84890095787
SN - 1083-7159
VL - 18
SP - 1270
EP - 1277
JO - Oncologist
JF - Oncologist
IS - 12
ER -