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. 2010:2010:162363.
doi: 10.1155/2010/162363. Epub 2010 Mar 28.

Molecular profiling of endometrial malignancies

Norasate Samarnthai  1 , Kevin Hall, I-Tien Yeh
Affiliations

Molecular profiling of endometrial malignancies

Norasate Samarnthai et al. Obstet Gynecol Int. 2010.

Abstract

Molecular profiling of endometrial neoplasms reveals genetic changes in endometrial carcinomas that support the dualistic model, in which type I carcinomas are estrogen-dependent, low grade lesions and type II carcinomas are nonestrogen dependent and high grade. The molecular changes in type I endometrial carcinomas include mutations in PTEN, PIK3CA, KRAS, and beta-catenin, along with microsatellite instability, whereas type II endometrial carcinomas are characterized by genetic alterations in p53, HER2/neu, p16, and E-cadherin. For endometrial neoplasms with a malignant mesenchymal component, C-MYC mutations and loss of heterozygosity are frequently seen in carcinosarcomas, and a fusion gene, JAZF1/JJAZ1, is distinctive for endometrial stromal sarcoma. In addition, p53 mutations may play an important role in tumorigenesis of undifferentiated endometrial sarcoma. These molecular changes can help in the diagnosis of endometrial neoplasms, as well as form the basis of molecular targeted therapy.

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Figures

Figure 1
Figure 1
The prototypes for the dualistic model of endometrial carcinoma. Type I endometrioid endometrial carcinoma shows glands lined by stratified neoplastic columnar cells (a), ×100; and type II serous carcinoma showing papillary structures and high nuclear grade (b), ×100.
Figure 2
Figure 2
A progression model for endometrioid carcinoma. Tumor initiation and progression are characterized by acquisition of various molecular alterations. PTEN alterations appear central to the initiation of proliferative lesions that then acquire mutations in other cancer-causing genes (e.g., DNA mismatch repair genes, KRAS, β-catenin) in the carcinogensis. An alternative pathway bypasses atypical hyperplasia and low-grade carcinoma to high-grade carcinoma by p53 mutation and HER2/neu amplification. NE, normal endometrium; EH, endometrial hyperplasia without hyperplasia, AH, atypical endometrial hyperplasia; EIC, endometrial intraepithelial carcinoma; LG-ECC, low grade endometrioid endometrial carcinoma; HG-ECC, high grade endometrioid endometrial carcinoma.
Figure 3
Figure 3
A progression model for nonendometrioid (type II) carcinomas. p53 mutations play a critical role in the conversion of atrophic endometrium to an intraepithelial form of serous carcinoma. NE, normal endometrium; EIC, endometrial intraepithelial carcinoma; NEEC, non-endometrioid endometrial carcinoma.
Figure 4
Figure 4
Carcinosarcoma is composed of two malignant components, carcinomatous and sarcomatous. The epithelial component is usually high grade carcinoma for example, serous/clear cell type. The mesenchymal part comprises either homologous (a), ×100 or heterologous element for example, cartilage or bone. Chondrosarcomatous element (∗) is present in (b), ×100.
Figure 5
Figure 5
Endometrial stromal sarcoma, low grade is circumscribed from the surrounding myometrium (a), ×40; and higher magnification of endometrial stromal sarcoma shows round uniform tumor cells resembling the stroma of proliferative endometrium with low mitotic rate (b), ×200.
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