Endometrial Carcinomas in Women Age 40 Years and Younger
K Garg, K Shih, R Barakat, RA Soslow. Memorial Sloan Kettering Cancer Center, New York, NY
Background: Endometrial carcinomas (ECs) in young women ( 40 yrs) are usually managed conservatively in selected patients. Whether oophorectomy with total hysterectomy is mandated for patients failing hormonal therapy is controversial. Recognition of features that might discourage conservative management and ovarian preservation are currently poorly characterized. We studied the presence of synchronous ovarian cancers and DNA mismatch repair (MMR) protein defects in this patient population.
Design: All ECs in women 40 years of age or younger were identified from review of institutional databases (1993-present) . All available slides were reviewed and DNA MMR immunohistochemistry (IHC) was performed using 4 markers (MLH1, PMS2, MSH2, MSH6) in cases with available blocks (n=56). Clinical information was obtained from electronic medical records.
Results: We identified 71 cases of ECs who underwent hysterectomy. ECs were predominantly endometrioid (65/71) and most were low grade (FIGO grade 1-2 = 83%). 8.5% were undifferentiated carcinomas (UCs). Most patients presented at early stage (stage I-II: 88%). A significant number of patients also had synchronous ovarian carcinomas (9/71 = 12%), predominantly endometrioid (7 of 9) while 2 were ovarian clear cell carcinomas (CCC). IHC for DNA MMR showed loss of at least one protein in 9 cases (16%) with slight predominance of MSH2/MSH6 abnormalities (5 of 9) compared to loss of MLH1/PMS2. The presence of defined histologic characteristics associated with microsatellite instability (MSI) (i.e LUS tumor, UCs, presence of tumor infiltrating lymphocytes) were noted in 8 of 9 tumors that showed loss of DNA MMR by IHC. None of the cases with synchronous ovarian and endometrial endometrioid carcinomas showed loss of DNA MMR. One of 2 ECs with synchronous CCC of ovary showed loss of MSH2/MSH6 while IHC for DNA MMR was not performed in the 2nd case. There were a total of 5 LUS tumors of which 4 showed loss of a DNA MMR protein.
Conclusions: Most ECs in young women are of endometrioid histology, well to moderately differentiated and present at early stage. However, UCs of the endometrium can also be seen in this age group. A significant proportion of these tumors showed loss of DNA-MMR by IHC. Synchronous endometrioid carcinomas of the ovary are frequent in this patient group, and this appears to be unrelated to DNA-MMR defects when both tumors are endometrioid. The presence of defined tumor characteristics, both gross and microscopic, appear to be powerful predictors of the possibility of MSI.
Tuesday, March 10, 2009 8:30 AM
Platform Session: Section D, Tuesday Morning