Koah R Vierkoetter1, Asia R Ayabe2, Maya VanDrunen3, Hyeong Jun Ahn4, David M Shimizu2, Keith Y Terada3. 1. Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. Electronic address: koah@hawaii.edu. 2. Department of Pathology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. 3. Department of Obstetrics, Gynecology, and Women's Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA. 4. Biostatistics Core, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
Abstract
OBJECTIVE: Patients with Lynch Syndrome are at an increased risk for a variety of malignancies, including ovarian cancer. Ovarian cancers associated with Lynch Syndrome are predominantly clear cell or endometrioid in histology. Lynch Syndrome is characterized by germline mutations in mismatch repair (MMR) genes. The current study aims to assess the prevalence of loss of MMR expression in patients with endometrioid and clear cell ovarian carcinoma. METHODS: A retrospective review identified 90 patients with endometrioid and/or clear cell carcinomas. Slides made from tumor tissue microarray blocks were evaluated using immunohistochemical stains with antibodies against MLH1, PMS2, MSH2, and MSH6. Statistical analysis was performed. RESULTS: Seven of the 90 cases (7.8%) had loss of MMR expression. The mean age of patients with loss of MMR expression (47 years) was significantly younger than those with retained MMR expression (p=0.014). Loss of MMR expression was present in 20% of patients under the age of 53 with clear cell or endometrioid cancers. Genetic studies found that 3 of the 5 patients with loss of MMR expression carried mutations consistent with Lynch Syndrome; acquired hypermethylation of MLH1 was noted in one patient. Six of 7 patients (86%) whose tumors lacked MMR expression had synchronous or metachronous primary malignancies, a significantly greater prevalence than those with retained MMR expression (p<0.001). CONCLUSION: Patients under the age of 53 with clear cell or endometrioid ovarian carcinomas are at a clinically significant risk for loss of MMR expression and Lynch Syndrome; routine screening with immunohistochemical staining should be considered.
OBJECTIVE:Patients with Lynch Syndrome are at an increased risk for a variety of malignancies, including ovarian cancer. Ovarian cancers associated with Lynch Syndrome are predominantly clear cell or endometrioid in histology. Lynch Syndrome is characterized by germline mutations in mismatch repair (MMR) genes. The current study aims to assess the prevalence of loss of MMR expression in patients with endometrioid and clear cell ovarian carcinoma. METHODS: A retrospective review identified 90 patients with endometrioid and/or clear cell carcinomas. Slides made from tumor tissue microarray blocks were evaluated using immunohistochemical stains with antibodies against MLH1, PMS2, MSH2, and MSH6. Statistical analysis was performed. RESULTS: Seven of the 90 cases (7.8%) had loss of MMR expression. The mean age of patients with loss of MMR expression (47 years) was significantly younger than those with retained MMR expression (p=0.014). Loss of MMR expression was present in 20% of patients under the age of 53 with clear cell or endometrioid cancers. Genetic studies found that 3 of the 5 patients with loss of MMR expression carried mutations consistent with Lynch Syndrome; acquired hypermethylation of MLH1 was noted in one patient. Six of 7 patients (86%) whose tumors lacked MMR expression had synchronous or metachronous primary malignancies, a significantly greater prevalence than those with retained MMR expression (p<0.001). CONCLUSION:Patients under the age of 53 with clear cell or endometrioid ovarian carcinomas are at a clinically significant risk for loss of MMR expression and Lynch Syndrome; routine screening with immunohistochemical staining should be considered.
Authors: Noralane M Lindor; Lawrence J Burgart; Olga Leontovich; Richard M Goldberg; Julie M Cunningham; Daniel J Sargent; Catherine Walsh-Vockley; Gloria M Petersen; Michael D Walsh; Barbara A Leggett; Joanne P Young; Melissa A Barker; Jeremy R Jass; John Hopper; Steve Gallinger; Bharati Bapat; Mark Redston; Stephen N Thibodeau Journal: J Clin Oncol Date: 2002-02-15 Impact factor: 44.544
Authors: Gad Singer; Thore Kallinowski; Arndt Hartmann; Wolfgang Dietmaier; Peter J Wild; Peter Schraml; Guido Sauter; Michael J Mihatsch; Holger Moch Journal: Int J Cancer Date: 2004-11-20 Impact factor: 7.396
Authors: Jinsong Liu; Constance T Albarracin; Ki-Hong Chang; Jennifer A Thompson-Lanza; Wenxin Zheng; David M Gershenson; Russell Broaddus; Rajyalakshmi Luthra Journal: Mod Pathol Date: 2004-01 Impact factor: 7.842
Authors: John P Geisler; Michael J Goodheart; Anil K Sood; Richard J Holmes; Melanie A Hatterman-Zogg; Richard E Buller Journal: Cancer Date: 2003-11-15 Impact factor: 6.860
Authors: Carlos Parra-Herran; Jordan Lerner-Ellis; Bin Xu; Sam Khalouei; Dina Bassiouny; Matthew Cesari; Nadia Ismiil; Sharon Nofech-Mozes Journal: Mod Pathol Date: 2017-08-04 Impact factor: 7.842
Authors: Alain G Zeimet; Harald Mori; Edgar Petru; Stephan Polterauer; Alexander Reinthaller; Christian Schauer; Tonja Scholl-Firon; Christian Singer; Katharina Wimmer; Johannes Zschocke; Christian Marth Journal: Arch Gynecol Obstet Date: 2017-05-16 Impact factor: 2.344