Clinical and pathologic features of young endometrial cancer patients with loss of mismatch repair expression

• Published in: Gynecologic oncology 2012-09, Vol.126 (3), p.408-412
• Main Authors: Grzankowski, Kassondra S, Shimizu, David M, Kimata, Chieko, Black, Michael, Terada, Keith Y
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Adenocarcinoma - ethnology; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenosine Triphosphatases - metabolism; Adult; Asian Continental Ancestry Group - genetics; Body mass index; Carcinosarcoma - ethnology; Carcinosarcoma - genetics; Carcinosarcoma - pathology; DNA Mismatch Repair; DNA Repair Enzymes - metabolism; DNA-Binding Proteins - metabolism; Endometrial cancer; Endometrial Neoplasms - ethnology; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; European Continental Ancestry Group - genetics; Female; Hematology, Oncology and Palliative Medicine; Humans; Lymphatic Metastasis; Microsatellite instability; Middle Aged; Mismatch repair; Mismatch Repair Endonuclease PMS2; MLH1/PMS2; MSH6/MSH2; MutL Protein Homolog 1; MutS Homolog 2 Protein - metabolism; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Nuclear Proteins - metabolism; Obstetrics and Gynecology; Oceanic Ancestry Group - genetics; Retrospective Studies
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2012.05.019

Abstract Objective This study examines premenopausal and early menopause patients in a unique population with endometrial cancer and loss of mismatch repair (MMR) gene expression. The purpose is to compare clinical and pathologic differences in patients with loss of expression (LOE) to those with normal expression (NE). Methods Endometrial cancer patients under age 60 in-between 1998 and 2008 were identified from a single tumor registry. Clinical and pathologic data were abstracted from records. Staining for expression of MSH6, MSH2, MLH1, and PMS2 were performed on archived tissue blocks. Statistical analysis was performed. Results 158 patients were analyzed; 58% Asian, 34% Pacific Islander, and 8% Caucasian. 31 demonstrated LOE of at least one MMR gene; 127 retained NE. 50% Caucasian, 21.9% Asian, and 12.5% Pacific Island populations had LOE of one or more MMR genes. LOE was found to have a higher incidence of Grade III (p = 0.0013) and stage 3–4 tumors (p = 0.0079), mean depth of myometrial invasion (p = 0.0019), lymphovascular space invasion (p = 0.0020), nodal metastases (p = 0.0157), and a lower incidence of Grade I (p = 0.0020) and stage 1A tumors (p = 0.0085). LOE had a significantly lower mean BMI (p = 0.0001). 35% of patients in the NE vs zero in the LOE group had a BMI greater than 40. Conclusion Younger patients with LOE endometrial cancer appear to represent a clinically significant subgroup of patients without features characteristically found in classic type 1 endometrial cancer generally demonstrating lower BMI and tumors associated with poor prognostic characteristics. It is unclear if the distinctive ethnicity found in Hawaii has a significant impact on outcome. Further investigation is necessary to identify appropriate treatment strategies.