[1006] Microsatellite Instability in Advanced Stage Endometrial Endometrioid Adenocarcinoma Is Associated with a Poor Prognosis.

Scott H Bradshaw, Russell Broaddus, Larissa Meyer, Bojana Djordjevic. Ottawa University, Ottawa, ON, Canada; M.D. Anderson Cancer Center, Houston, TX

Background: Microsatellite instability (MSI) arises due to loss of function of mismatch repair (MMR) proteins, commonly MLH1, MSH2 and MSH6, either through genetic loss or epigenetic silencing. There are only a few and conflicting reports on the prognostic value of MSI in endometrial cancer. The aim of this study was to investigate this parameter in endometrioid endometrial tumors with the emphasis on early vs. advanced stage disease.
Design: Immunohistochemistry for MMR proteins, MLH1, MSH2 and MSH6, was performed in 100 endometrioid carcinoma cases. The patients, aged 28-92, had no known history of HNPCC. Immunohistochemistry was scored as positive or negative. Tumors with loss of any one of the three MMR proteins were classified as having MSI, with the remainder classified as microsatellite stable (MSS). Patients were grouped as early (I and II) and advanced (III and IV) stage. Outcomes including depth of myometrial invasion (MI), lymphovascular invasion (LVI), lymph node (LN) status, relapse free survival and overall survival were examined.
Results: The results are summarized in tables 1 and 2.

TABLE 1: OUTCOMES FOR STAGE I,II: MSS VS MSI

	MSS	MSI	p-value
% Alive at last follow-up	96	100	1.00
% Relapse free	73	79	0.7597
% With LVI	29	47	0.2488
% With LN+	0	0	N/A
Median depth of MI (%)	26	33	0.7912

TABLE 2: OUTCOMES FOR STAGE III,IV: MSS VS MSI

	MSS	MSI	p-value
% Alive at last follow-up	95	58	0.0159
% Relapse free	67	25	0.0324
% With LVI	71	100	0.1247
% With LN+	61	78	0.6673
Median depth of MI (%)	42	82	0.0283

MSI was identified in 31 patients (28 MLH1, 1 MSH2, 2 MSH6). Patients were of similar age in the early (59) and advanced stage (61) groups. Unlike the early stage tumors, advanced stage tumors with MSI had significantly shorter overall survival and relapse free survival rates, as well as a greater depth of MI. They also showed a trend toward a higher incidence of LVI and LN metastases. In addition, MSI was significantly more common in grade 3 tumors (58%) than in grade 1 and 2 tumors (30%) (p=0.0441).
Conclusions: Advanced stage endometrioid endometrial carcinomas with MSI are associated with a worse prognosis than their MSS counterparts. MSI may predispose tumors toward an accelerated pace of acquisition of new mutations, leading to more aggressive tumor behavior in advanced stages. As such, identification of MSI in endometrioid endometrial tumors may be instrumental in guiding patient management.
Category: Gynecologic & Obstetrics

Monday, February 28, 2011 2:15 PM

Platform Session: Section C, Monday Afternoon