Kevin M Elias1, S Intidhar Labidi-Galy2, Allison F Vitonis3, Jason L Hornick4, Leona A Doyle4, Michelle S Hirsch5, Daniel W Cramer6, Ronny Drapkin7. 1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA. 2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. 3. Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA. 4. Harvard Medical School, Boston, MA, USA; Brigham and Women's Hospital, Department of Pathology, Boston, MA, USA. 5. Harvard Medical School, Boston, MA, USA; Brigham and Women's Hospital, Department of Pathology, Boston, MA, USA; Brigham and Women's Hospital, Division of Women's and Perinatal Pathology, Boston, MA, USA. 6. Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. 7. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Brigham and Women's Hospital, Department of Pathology, Boston, MA, USA; Brigham and Women's Hospital, Division of Women's and Perinatal Pathology, Boston, MA, USA. Electronic address: ronny_drapkin@dfci.harvard.edu.
Abstract
BACKGROUND: Due to concern that mucinous malignant or borderline ovarian neoplasms (MON) may represent metastatic deposits from appendiceal primaries, gynecologic oncologists routinely perform appendectomy in these cases. However, a multidisciplinary critique of this practice is lacking. METHODS: The New England Case-Control study database was utilized to compare the effect of prior appendectomy against known risk factors for MON. Pathology and operative reports of local cases of MON were reviewed to estimate the frequency of microscopic mucinous lesions in the appendix. Protein expression patterns among mucinous ovarian, colorectal, and appendiceal cancers were compared by immunohistochemistry. RESULTS: From the New England Case-Control study, 287 cases of MON were compared against 2339 age-matched controls. Prior appendectomy did not reduce the risk of MON (OR 1.28, 95% CI 0.83-1.92, p = 0.23), while prior tubal ligation, parity, and breastfeeding were each protective against MON. Active smoking (OR 2.04, 95% CI 1.48-2.80, p < 0.001) was associated with an increased risk of MON. Among 196 mucinous adnexal tumors, appendectomy did not reclassify any MON as appendiceal in origin. By immunohistochemistry, mucinous ovarian carcinomas tended to be CK7+/CK20-/MUC2-/CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were typically CK7-/CK20+/MUC2+/CDX2+, although with some overlap in immunophenotype. Additionally, PAX8 was positive in a subset of MOC and negative in all appendiceal carcinomas. CONCLUSION: Prior appendectomy is not protective against development of malignant or borderline MON. Routine appendectomy during surgery for MON seldom reveals an unsuspected GI primary in early stage tumors but may aid in final diagnosis in advanced stage cases. FUNDING: National Cancer Institute grants P50-CA105009 and R21 CA-156021; The Honorable Tina Brozman 'Tina's Wish' Foundation; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF); Dana-Farber Cancer Institute - Susan Smith Center for Women's Cancers; Robert and Deborah First Fund; The Gamel Family Fund; Mary Kay Foundation; Sandy Rollman Ovarian Cancer Foundation; Arthur Sachs/Fulbright/Harvard; La Fondation Philippe; La Fondation de France.
BACKGROUND: Due to concern that mucinous malignant or borderline ovarian neoplasms (MON) may represent metastatic deposits from appendiceal primaries, gynecologic oncologists routinely perform appendectomy in these cases. However, a multidisciplinary critique of this practice is lacking. METHODS: The New England Case-Control study database was utilized to compare the effect of prior appendectomy against known risk factors for MON. Pathology and operative reports of local cases of MON were reviewed to estimate the frequency of microscopic mucinous lesions in the appendix. Protein expression patterns among mucinous ovarian, colorectal, and appendiceal cancers were compared by immunohistochemistry. RESULTS: From the New England Case-Control study, 287 cases of MON were compared against 2339 age-matched controls. Prior appendectomy did not reduce the risk of MON (OR 1.28, 95% CI 0.83-1.92, p = 0.23), while prior tubal ligation, parity, and breastfeeding were each protective against MON. Active smoking (OR 2.04, 95% CI 1.48-2.80, p < 0.001) was associated with an increased risk of MON. Among 196 mucinous adnexal tumors, appendectomy did not reclassify any MON as appendiceal in origin. By immunohistochemistry, mucinous ovarian carcinomas tended to be CK7+/CK20-/MUC2-/CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were typically CK7-/CK20+/MUC2+/CDX2+, although with some overlap in immunophenotype. Additionally, PAX8 was positive in a subset of MOC and negative in all appendiceal carcinomas. CONCLUSION: Prior appendectomy is not protective against development of malignant or borderline MON. Routine appendectomy during surgery for MON seldom reveals an unsuspected GI primary in early stage tumors but may aid in final diagnosis in advanced stage cases. FUNDING: National Cancer Institute grants P50-CA105009 and R21 CA-156021; The Honorable Tina Brozman 'Tina's Wish' Foundation; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (AMRF); Dana-Farber Cancer Institute - Susan Smith Center for Women's Cancers; Robert and Deborah First Fund; The Gamel Family Fund; Mary Kay Foundation; Sandy Rollman Ovarian Cancer Foundation; Arthur Sachs/Fulbright/Harvard; La Fondation Philippe; La Fondation de France.
Authors: Julia Timofeev; Mary T Galgano; Mark H Stoler; Jason A Lachance; Susan C Modesitt; Amir A Jazaeri Journal: Obstet Gynecol Date: 2010-12 Impact factor: 7.661
Authors: Colleen M Feltmate; Kenneth R Lee; Michael Johnson; John O Schorge; Kwong-Kwok Wong; Ke Hao; William R Welch; Debra A Bell; Ross S Berkowitz; Samuel C Mok Journal: Clin Cancer Res Date: 2005-11-01 Impact factor: 12.531
Authors: Tomer Feigenberg; Allan Covens; Zeina Ghorab; Nadia Ismiil; Valérie Dubé; Reda S Saad; Mahmoud A Khalifa; Sharon Nofech-Mozes Journal: Int J Gynecol Cancer Date: 2013-09 Impact factor: 3.437
Authors: Kevin M Elias; Petros Tsantoulis; Jean-Christophe Tille; Allison Vitonis; Leona A Doyle; Jason L Hornick; Gurkan Kaya; Laurent Barnes; Daniel W Cramer; Giacomo Puppa; Sarah Stuckelberger; Jagmohan Hooda; Pierre-Yves Dietrich; Michael Goggins; Candace L Kerr; Michael Birrer; Michelle S Hirsch; Ronny Drapkin; Sana Intidhar Labidi-Galy Journal: J Pathol Date: 2018-10-19 Impact factor: 7.996
Authors: Emily K Adler; Rosario I Corona; Janet M Lee; Norma Rodriguez-Malave; Paulette Mhawech-Fauceglia; Heidi Sowter; Dennis J Hazelett; Kate Lawrenson; Simon A Gayther Journal: Oncotarget Date: 2017-11-27