[1167] Endometrial Carcinomas with DNA Mismatch Repair Abnormalities: Analysis of 75 Cases

Yaser R Hussein, Karuna Garg, Robert A Soslow, Deborah DeLair. Memorial Sloan-Kettering Cancer Center, New York, NY; UCSF, San Francisco, CA

Background: Endometrial carcinoma (EC) can be associated with defective DNA mismatch repair (MMR) in ∼20% of patients. The morphologic differences in tumors with loss of MLH1/PMS2 versus MSH2/MSH6 by immunohistochemistry (IHC) have not been well described.
Design: All ECs with abnormal IHC for MMR with slides available (2006-present) were reviewed. A total of 75 patients were identified. All available slides were reviewed. Clinical history was obtained from electronic medical records.
Results: The clinicopathologic characteristics of each group are described.

Clinicopathologic characteristics of the 2 groups of patients
VariableMLH1/PMS2 loss (n=42)MSH2/MSH6 loss (n=33)
AgeMean 57 (27-78)Mean 52 (34-69)
Histologic subtypeEndometrioid26 (63%)23 (76%)
 Clear cell carcinoma02 (6%)
 Un/dedifferentiated11 (27%)1 (3%)
 MMT1 (2%)1 (3%), focal
 Mixed endometrioid/clear cell/undifferentiated1 (2%)2 (6%)
 Mixed endometrioid/clear cell1 (2%)2 (6%)
 Mixed endometrioid/mucinous01 (3%)
FIGO grade (for endometrioid)I4 (15%)8 (35%)
 II16 (62%)11 (48%)
 III6 (23%)4 (17%)
FIGO stageI25 (60%)16 (48%)
 II5 (12%)2 (6%)
 III/IV11 (28%)15 (46%)
Lymphovascular invasion24 (57%)15 (45%)
Myometrial invasion35 (83%)27 (82%)
MELF inasion29/35 (83%)16/27 (59%)
Heterogeneity26 (62%)15 (45%)
Mucinous differentiation29 (69%)20 (61%)
Intratumoral lymphocytes38 (90%)30 (91%)
Peritumoral lymphocytes34 (81%)25 (76%)
LUS involvement14 (33%)9 (27%)
Synchronous ovarian carcinoma1 (endometrioid)1(endometrioid);1 MMT(endometrioid/clear cell/rhabdomyosarcoma); 1(mucinous/endometrioid/undifferentiated);1(clear cell)
Atrophic endometrium11 (26%)7 (21%)
Genetic testing1 (MLH1 mutation); 2(PMS2 mutation); 7 (MLH1 hypermethylation); 2 negative2 (MSH2 mutation); 4 (MSH6 mutation);2 (MSI-high); 3 negative

Conclusions: Patients with EC and MSH2/MSH6 defects by IHC tend to present at a higher stage, compared to patients with MLH1/PMS2 loss. Un/dedifferentiated carcinomas are more likely to demonstrate MLH1/PMS2 loss, while tumors with a clear cell component are more likely to show MSH2/MSH6 loss. MELF (microcystic, elongated, fragmented) pattern of myometrial invasion is more frequent in patients with MLH1/PMS2 loss. Finally, synchronous ovarian carcinoma tends to occur more frequently in MSH2/MSH6 loss and show a variety of histologies.
Category: Gynecologic & Obstetrics

Monday, March 4, 2013 8:30 AM

Proffered Papers: Section E, Monday Morning


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