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Impact of molecular alterations and targeted therapy in appendiceal adenocarcinomas.

ABSTRACT:

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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.

SUBMITTER: Raghav KP

PROVIDER: S-EPMC3868421 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Impact of molecular alterations and targeted therapy in appendiceal adenocarcinomas.

Raghav Kanwal P S KP Shetty Aditya V AV Kazmi Syed M A SM Zhang Nianxiang N Morris Jeffrey J Taggart Melissa M Fournier Keith K Royal Richard R Mansfield Paul P Eng Cathy C Wolff Robert A RA Overman Michael J MJ

The oncologist 20131022 12

<h4>Unlabelled</h4>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).<h4>Patients and methods</h4>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 follo ...[more]

PMID: 24149137

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Dataset Information

Impact of molecular alterations and targeted therapy in appendiceal adenocarcinomas.

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Patients and methods

Results

Conclusion

Publications

Impact of molecular alterations and targeted therapy in appendiceal adenocarcinomas.

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