Endometrial Cancer

Abstract

Endometrial cancer is the most common malignancy of the female genital tract in the US. Immunohistochemistry and genomic studies have led to key insights into the pathogenesis of endometrial carcinoma and have provided a genetic basis for the current dualistic classification of this common malignancy. This classification has been challenged by the recent The Cancer Genome Atlas study, which has pursued a molecular classification that permits classification of all endometrial cancer tumours.

Key Concepts:

  • Dualistic classification is the most valid tool to categorise endometrial carcinomas since 1983.

  • Type‐I endometrial cancers are mostly oestrogen dependent. They are low‐grade and low‐stage tumours and present slow evolution and better prognosis than type‐II tumours.

  • Type‐II endometrial cancers are not dependent on hormones. They are high‐grade and aggressive tumours.

  • Type‐I is composed of endometrioid tumours, whereas type‐II is mostly composed of serous histologies and other minor subtypes.

  • Precursor lesions of type‐I and type‐II carcinomas are hyperplasia and intraepithelial carcinoma, respectively.

  • The most common alterations identified in type‐I carcinomas include PTEN, PIK3CA, CTNNB1, KRAS, FGFR2 and SPRY‐2 mutations and microsatellite instability.

  • The mutated genes identified in type‐II carcinomas include TP53, PIK3CA, PPP2R1A, Her2/neu, E‐cadherin, CCNE1 and BRCA1, among others.

  • High‐grade tumours and tumours with mix histologies are difficult to allocate in the dualistic model as they present overlapping or combined morphologic and molecular characteristics from both types.

  • TCGA molecular classification permits the categorisation of all endometrial tumours into 4 categories: POLE ultramutated, MSI hypermutated, copy number low and copy number high.

  • More studies are needed in order to validate the usefulness of the recent molecular classification.

Keywords: endometrioid carcinoma; serous carcinoma; dualistic model; TCGA ; molecular classification; PTEN ; P53; microsatellite instability

Figure 1.

Clinicopathological features of type‐I and type‐II endometrial carcinomas with photomicrographs of the most common histologies representing each type: on the left, picture of an endometrioid histology; on the right, picture of a serous histology.

Figure 2.

Model for endometrial tumourigenesis through two divergent pathways and the genetic alterations associated with each step.

Figure 3.

Schematic view of the molecular classification of endometrial cancer, including name, main characteristics of the groups and main mutations.

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Further Reading

Lax SF and Kurman R (1997) A dualistic model for endometrial carcinogenesis based on immunohistochemical and molecular genetic analyses. Verhandlungen der Deutschen Gesellschaft für Pathologie 81: 228–232.

Sherman ME (2000) Theories of endometrial carcinogenesis: a multidisciplinary approach. Modern Pathology 13: 295–308.

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Reventos, Jaume, Colas, Eva, Martínez, Elena, Campoy, Irene, Devis, Laura, Rigau, Marina, Olivan, Mireia, Cabrera, Silvia, Gil‐Moreno, Antonio, Garcia, Angel, Doll, Andreas, Castellvi, Josep, and Díaz‐Feijoo, Berta(Dec 2013) Endometrial Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006108.pub2]