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High-tech (en) (3779)

Impact of Molecular Alterations and Targeted Therapy in Appendiceal Adenocarcinomas

Tue Dec 17, 2013 12:49 Share


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.


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.


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.

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Born in 1964, business owner, from Woodbridge, VA, owns ExcitingAds! Inc. ( and blog ( He was born in Mirpurkhas, Sind, Pakistan. His elementary school was ST. Michael's Convent High School, Mirpurkhas, Sind, Pakistan. Graduated high school from ST. Bonaventure's Convent High School, Hyderabad, Sind, Pakistan. His pre-med college was S. A. L. Govt. College, Mirpurkas, Sind, Pakistan. Graduated from Liaquat University of Medical and Health Sciences, Jamshoro, Sind, Pakistan in 1990. Earned equivalency certification from Educational Commission for Foreign Medical Graduates, Philadelphia, PA in 1994.

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