[1246] Endometrial Carcinoma with Mucinous Differentiation and Kras G12D Mutation Is Associated with Lymph Node Metastasis and Vaginal Recurrence

Jinjun Xiong, Mai He, Cynthia Jackson, Virginia Breese, C James Sung, Margaret M Steinhoff, M Ruhul Quddus, Trevor Tejadaberges, W Dwayne Lawrence. Women & Infants Hospital, Providence, RI; Rhode Island Hospital, Providence, RI; Alpert Medical School of Brown University, Providence, RI

Background: Oncogenic mutation of Kras gene is critical for the development of multiple malignancies. Our previous studies showed endometrial carcinomas with significantly mucinous differentiation are associated with higher frequency of Kras mutations. A recent publication suggested that mucinous histology is a risk factor for nodal metastases. The current study investigated the correlation between mucinous histology and/or Kras mutations to lymph node metastasis and vaginal recurrence.
Design: Pathology archives were examined for cases of ECMD; 28 cases were identified and 16 endometrioid carcinoma without mucinous differentiation (EC) were chosen as controls. Data abstraction revealed 21 cases with lymph node (LN) examination and 4 vaginal recurrences. Cases with LN examination or vaginal recurrence were analyzed by PCR for Kras codon 12 and 13.
Results: Of the 21 cases with LN examination, 14 had ECMD and 7 EC. 5 were positive for metastasis, all in cases of ECMD (5/14, 35%). Ten cases had Kras mutations detected (8 (57%) ECMD and 2 (29%) EC). There was overlap of LN metastasis and Kras mutation in three (60%) of the 5 ECMD cases with LN metastasis. All harbored the G12D Kras mutation. G12D is significantly associated with LN metastasis compared to wild type and/or other types of Kras mutation (P<0.05 and P<0.001, respectively).

Table 1. Lymph node positivity and Kras mutation status in ECMD and controls.
Kras mutation8/142/7

Four cases of vaginal recurrence were identified, including 3 (3/28, 11%) ECMD and 1 (1/16, 6%) EC. Among these 4 cases, Kras mutations were detected in 2 of the 3 (2/3, 67%) ECMD with one G12V and one G12D, and one (1/1, 100%) EC with G13D.

Table 2. Vaginal recurrence and Kras mutation status in ECMD and controls.
Vaginal recurrence3/281/16
Kras mutation2/31/1

Conclusions: Kras G12D mutation is associated with higher frequency of LN metastasis. Our result suggests that Kras G12D may be associated with more aggressive biological behavior. The fact that all LN metastasis cases are associated with significant mucinous differentiation supports recent finding of mucinous morphology associated with more LN metastasis. Recurrence of low grade EC is uncommon, however, we found that 11% of ECMD had vaginal recurrence and, of these, 67% harbored a KRAS mutation.
Category: Gynecologic & Obstetrics

Monday, March 4, 2013 9:15 AM

Proffered Papers: Section E, Monday Morning


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