Are there different types of endometrial cancer?

Posted in endometrial cancer, uterine cancer; Posted 2 months ago by Andreas Obermair

There are different types of endometrial cancer, and until now they have been classified based on the histological characteristics of the cancer cells.

The two main types of endometrial cancer were:

• Type 1 uterine cancer (Endometrioid Adenocarcinoma): This was the most common type of endometrial cancer, accounting for about 80-90% of cases. It typically arises from the cells that form the lining of the uterus (endometrium). Endometrioid adenocarcinoma is often associated with excess estrogen exposure, obesity, and conditions such as diabetes and polycystic ovary syndrome (PCOS).
• Type 2 uterine cancer Serous Adenocarcinoma: This type was less common but tends to be more aggressive than endometrioid adenocarcinoma. Serous adenocarcinoma is less associated with excess estrogen and is more common in older women. It tends to grow more rapidly and is often diagnosed at a later stage.

There are also some less common subtypes of endometrial cancer, including:

• Clear Cell Carcinoma: This subtype is less common than endometrioid adenocarcinoma and serous adenocarcinoma. It has a distinct appearance under the microscope and is often associated with a poorer prognosis.
• Mucinous Adenocarcinoma: This subtype is rare and is characterized by the presence of mucin, a slimy substance, in the cancer cells.
• Undifferentiated/Dedifferentiated Carcinoma: This is a high-grade and aggressive subtype of endometrial cancer where the cancer cells are poorly differentiated or undifferentiated.

New classification systems go beyond the histopathological characteristics and take genetic tumour mutations into account.

Genomic testing in endometrial cancer has emerged as a potentially important tool for personalized medicine, to improve the diagnosis of endometrial cancer and treatment strategies. By analysing the genetic makeup of tumours, gynaecological oncologists can identify specific mutations and alterations that drive cancer growth, offering valuable insights into disease prognosis. The evidence to guide targeted therapies is currently still immature and unknown.

The two main types of genomic testing in endometrial cancer are microsatellite instability (MSI) or mismatch repair (MMR) testing, testing for p53 and for POLE.  

MMR testing helps in the identification of Lynch syndrome, a hereditary condition linked to endometrial and bowel cancer. However, MMR testing is also important because a new group of medications have become available recently that is enormously effective in patients with MMR-deficient tumours. Some of the cancer “miracle cures” can be attributed to these targeted treatments. Currently, the two main issues with these treatments are that:

1. We don't know enough about side effects and complications from these treatments (adverse reactions may be severe sometimes); and

2. What type of patients should be offered these very expensive medications.

P53 testing is nowadays performed for all endometrial cancer cases in my practice. Mutations I p53 indicate aggressive tumour types but it remains unknown whether these patients benefit from intensified treatment and whether their survival can be improved.

POLE testing is useful in patients who have “aggressive” tumours by old standards. In 10% of these patients a POLE mutation can be found and in those cases it indicates that the tumour is actually not aggressive and patients can be spared intense treatments. POLE testing is expensive and for that reason currently not offered routinely in Australia. In my practice, I offer POLE testing to endometrial cancer patients who I believe could be spared intense treatment but those patients will need to pay for the test themselves.

In summary, these genomic insights not only assist in refining prognosis but also will play a crucial role in tailoring treatment approaches in the future. Targeted therapies, such as those directed at specific genetic mutations, have shown promising results in improving outcomes for patients with endometrial cancer. Additionally, genomic testing helps identify individuals who may benefit from immunotherapy, a revolutionary treatment modality that harnesses the body's immune system to combat cancer cells.

The prognosis and treatment approach for endometrial cancer can vary based on the specific type and stage of the cancer. It's essential for individuals diagnosed with endometrial cancer to work closely with their healthcare team to determine the most appropriate treatment plan for their specific situation.

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