Investigation of Uterine Carcinosarcoma: Case Report and Cohort Analysis

Timothy N. Hembree, DO, PhD, Jamie K. Teer, PhD, Ardeshir Hakam, MD, and Alberto A. Chiappori, MD


Cancer Control. 2016;23(1):61-66. 

In This Article


The patient discussed in our case report presented in the sixth decade of life with stage 4 disease and more than 50% myometrial invasion, so her prognosis was poor. She was referred to our gynecological oncology clinic and received chemotherapy with carboplatin and paclitaxel. She tolerated 2 cycles of chemotherapy before she died from her disease.

Most women in our cohort were white and their stages of presentation were equally distributed throughout the group. This is in contrast to other epidemiological studies, which have included higher percentages of black or non–white women and those likely to present with advanced-stage disease.[20,21]

In our examination of mutations in 1,321 genes thought to be associated with cancer in a small cohort of individuals diagnosed with uterine carcinosarcoma (n = 9), we reproduced some earlier mutations. Direct comparisons of frequency between studies are limited by small sample size, but general similarities exist. Therefore, we can conclude that mutations in PIK3CA, KRAS, PTEN, TP53, ARID1A, KMT2C, and FBXW7 are important drivers of uterine carcinosarcoma. However, some differences in mutation frequencies are apparent, perhaps reflecting the pathological heterogeneity of this disease. The large number of potential driver genes suggests that uterine carcinosarcoma is a genetically heterogeneous disease.

Genetic investigation of additional samples will be needed to more accurately determine incidence, to identify lower-frequency genetic events, and to associate status with clinical phenotype. However, we observed a mutation in at least 1 well-characterized oncological gene for every sample analyzed, suggesting that, although uterine carcinosarcoma may be driven by heterogeneous events, these drivers are already known to be important for the development of other cancer types.

Given poor overall survival rates for uterine carcinosarcoma, genetic characterization offers the potential to improve our understanding and treatment of this rare type of cancer. Our preliminary investigation demonstrated that pathways altered in other cancer types are also altered here, suggesting that therapeutic options (including targeted therapies) may also be effective in uterine carcinosarcoma. We also confirmed the presence of mutations in chromatin-remodeling genes in this disease, suggesting a possible therapeutic strategy via histone deacetylase inhibitors.

In addition, we observed a POLE proofreading-domain mutation resulting in a large mutational load in uterine carcinosarcoma. Large mutation load has been linked to durable response to immune checkpoint–inhibitor therapy in non–small-cell lung cancer and melanoma, suggesting another possible strategy for this disease.[22,23] Future studies will also need to incorporate clinical outcome information to further understand the progression and prognosis of this malignant disease.