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Endometrial carcinoma, or endometrial cancer, is when malignant or cancer cells arise in
the glands of the endometrium, the lining of the uterus.
The uterus is a hollow organ that sits behind the urinary bladder and in front of the rectum.
The top of the uterus above the openings of the fallopian tubes is called the fundus,
and the region below the openings is called the uterine body.
The uterus tapers down into the uterine isthmus and finally the cervix, which protrudes into
the vagina.
Zooming into the cervix, there are two openings, a superior opening up top, and an inferior
opening down below, both of which have mucus plugs to keep the uterus closed off except
during menstruation and right before ovulation.
The uterus is anchored to the sacrum by utero-sacral ligaments, to the anterior body wall by round
ligaments, and it’s supported laterally by cardinal ligaments as well as the mesometrium,
which is part of the broad ligament.
The wall of the uterus has three layers: the perimetrium, which is a layer continuous with
the lining of the peritoneal cavity, the myometrium, which is made of smooth muscle that contracts
during childbirth to help push the baby out, and the endometrium, a mucosal layer, that
undergoes monthly cyclic changes.
The endometrium is itself made up of a single layer of simple columnar epithelium, which
has ciliated and secretory cells, that sit on top of connective tissue, or stroma.
There any many grooves in the stroma which is lined by the epithelium and these are the
uterine glands which secrete a glycogen rich fluid that’s essential for the developing
embryo during early pregnancy.
Endometrial carcinoma involves the abnormal growth of the epithelial cells that make up
endometrial glands, and there are two main types.
The most common is Type 1 endometrial carcinoma, which is also called endometrioid carcinoma
because the tumours grow in a way that looks like normal endometrial glands.
It usually involves several genetic mutations in endometrial cells, including of PTEN, a
tumor suppressor gene; PIK3CA, an oncogene; and ARID1A, a gene regulating chromatin structure.
All of these mutations increase signaling in the PI3K/AKT pathway, which promotes growth
and replication of endometrial cells.
More signaling in the PI3K/AKT pathway also enhances the expression of genes which are
linked to estrogen receptors.
So having high levels of estrogen will cause the endometrium undergoes hyperplasia, leading
to increased risk of developing type 1 endometrial carcinoma.
Now, excessive estrogen can come from obesity, because fat cells convert adrenal precursors
into sex hormones; taking tamoxifen, a breast cancer medication that blocks estrogen receptor
in the breasts, but stimulates them in the uterus; and postmenopausal estrogen therapy
given without a progestin to “balance” it out.
Other risk factors related to high estrogen levels are never having been pregnant; chronic
anovulation, when the ovaries don’t release an egg during a menstrual cycle; and having
many menstrual cycles.
Age is also a factor since endometrial carcinoma tends to develop in women who have gone through
menopause, usually around 55 to 65 years of age.
Finally, a hereditary condition called Hereditary nonpolyposis colorectal cancer, also called
Lynch syndrome, causes a high risk of developing certain cancers, including colon cancer and
endometrial carcinoma.
The good news is that there are actually factors that protect against Type 1 endometrial carcinoma!
Taking hormonal contraceptives, being older at the time you give birth, and breastfeeding
all reduce the risk of developing this type of cancer.
Now, type 2 endometrial carcinoma is more rare, and it has a number of subtypes.
The most common subtype is serous carcinoma.
The genetic mutations found most often in serous carcinoma involve the TP53 gene, another
tumor suppressor, and aneuploidy, or an abnormal number of chromosomes after cell division.
Type 2 carcinomas don’t appear to be linked with estrogen levels.
These cancers typically affect women who have endometrial atrophy and who have lower body
weight.
They also tend to develop later in life than Type 1 and are more common in women of African
descent.
Even though there are two distinct types of endometrial carcinomas, we use the same stages
to describe their development.
In stage 1, the carcinoma is only in the uterus.
In stage 2, it has spread to the cervix.
In stage 3, it has spread outside the uterus but is still within the lesser, or “true”
pelvis.
This means it could affect structures like the vagina and pelvic lymph nodes.
In stage 4, it has spread beyond the pelvis.
Most Type 1 endometrial carcinomas are diagnosed in stage 1 and aren’t very aggressive, and
because of that they have a good prognosis.
But type 2 carcinomas are trickier and much more aggressive and often spreads to other
parts of the body via the lymphatic system or the fallopian tubes.
The main symptom of endometrial carcinoma is abnormal vaginal bleeding, usually without
pain.
If it’s more advanced, there might be enlargement of the uterus if the tumor or tumors are large
enough, and this can cause abdominal pain and cramping.
Diagnosing endometrial carcinoma usually involves doing a transvaginal ultrasound to determine
if the endometrium is abnormally thick.
If it’s more than 4 millimetres thick, then a biopsy or a dilation and curettage procedure
is used to remove some endometrial cells and confirm the diagnosis.
Surgery is the treatment for all types and stages of endometrial carcinoma.
This typically means the removal of the uterus, both ovaries, and both fallopian tubes, also
called a hysterectomy with bilateral salpingo-oophorectomy, combined with the removal of pelvic and para-aortic
lymph nodes.
In some cases where the cancer is more advanced or is likely to spread, for example a Type
1 carcinoma that’s stage II and above and all Type 2 carcinomas, radiation therapy and/or
chemotherapy is also done after surgery.
All right, as a quick recap, endometrial carcinoma is a very common cancer of the lining of the
uterus.
Type 1 is associated with having abnormally high levels of estrogen over a long period
of time, and is usually preceded by endometrial hyperplasia.
Type 2, which has several subtypes, isn’t linked with estrogen levels, and is more aggressive
than type 1.
The most common symptom is abnormal vaginal bleeding after menopause and the treatment
is hysterectomy with bilateral salpingo-oophorectomy.