Prevalence of Lynch Syndrome among Unselected Endometrial Cancer Patients
Cristina Alenda, Cecilia Egoavil, Jose L Soto, Adela Castillejo, Victor M Barbera, Maria J Roman, Ana B Sanchez, Jose A Lopez, Oscar Pinero, Carla Guarinos, Lucia Perez-Carbonell, Maria Rodriguez, Gloria Peiro, Estefania Rojas, Maria J Gonzalez, Sonia Ciguenza, Juan C Martinez-Escoriza, Rodrigo Jover, Francisco I Aranda, Artemio Paya. University Hospital, Alicante, Spain; University Hospital, Elche, Spain
Background: Endometrial cancer (EC) is the most common cancer in women with Lynch syndrome (LS). The purpose of this study is to determine the frequency of Lynch syndrome among unselected incident cases of endometrial cancer.
Design: A total number of 178 consecutively and newly diagnosed EC patients were included in this study. Recruited patients were diagnosed and treated at the University Hospital of Alicante between years 2004-2009. All tumors were tested for microsatellite instability (MSI), immunohistochemistry of MLH1, MSH2, MSH6 and PMS2 (MisMatch Repair proteins) and BRAF V600E mutation. Methylation analysis of MLH1 gene promoter was performed in cases with loss of MLH1 expression. Germline mutation analysis of MMR genes was performed in all cases with molecular or immunohistochemistry alteration.
Results: Loss of MMR protein expression and/or MSI was evidenced in 70 cases (39.3%). Thirty four of these cases showed MLH1 methytation and were considered as sporadic tumors. Therefore, the remaining 36 cases were seen as suspected LS (10 MLH1 no methylated, 5 loss of MSH2/MSH6, 9 loss of MSH6, 1 loss of PMS2 and 10 MSI without loss of protein expression). Discordances between IHC and MSI were found in 25 cases (35.7%). None of the cases had BRAF mutation. Germline mutation analysis was completed in 17 out of 36 suspected cases. Patogenic germline mutation was found in 7 patients (1 in MLH1, 3 in MSH2, 2 in MSH6 and 1 in PMS2).
Conclusions: Our results show that at least 3.9% (7/178) of endometrial cancer patients have LS and the predicted frequency might be over 8% in Spanish population. Early LS diagnosis followed by intense cancer surveillance and/or prophylactic surgery can prevent morbidity and mortality from LS cancers. Further efforts focused on the increase of LS diagnosis are compulsory.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 139, Wednesday Morning