These are the most common type, accounting for approximately 80% of cases. They typically arise in the setting of endometrial hyperplasia and like endometrial hyperplasia they are associated with obesity, diabetes, hypertension, infertility and unopposed estrogen stimulation.
Sequencing of the genomes of type I endometrial carcinoma has shown that the most common mutations act to increase signaling through the P13K/AKT pathway. P13K/AKT signaling somehow augments expression of estrogen receptor-dependent target genes in endometrial cells. Among the mutations that impact the P13K/AKT pathway in endometrial carcinomas are the following:
- Mutation in the PTEN tumor suppressor gen
- PIK3CA an oncogene that encodes the catalytic subunit of P13K
- Mutations that activate KRAS, which stimulates P13K/AKT signaling
- Loss of function mutations in ARID1A
- Other mutations incl: TP53. DNA mismatch repair genes
Type II (Serous) Carcinoma
Type II tumors are by definition poorly differentiated tumors and account for approximately 15% of cases of endometrial carcinoma. Mutations in the tumor suppressor TP53 are present in at least 90% of serous endometrial carcinoma.
Clinical features
Carcinoma of the endometrium may be asymptomatic for a period of time, it usually produces irregular or postmenopausal vaginal bleeding with excessive leukorrhea (=a whitish or yellowish discharge of mucus from the vagina)
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