Endometrial Cancer
for laymen and students
Mario Kopljar, MD

Anatomy and physiology
Normal endometrium
Generally on cancerogenesis

Etiology and Pathogenesis
Spreading of EC
Grading and Staging
Early symptoms
Diagnostic process

Differential diagnosis
Prevention and Treatment

Generally on cancerogenesis
Go to the beginning

This is a very simplified overview of the factors that initiate cancer.

Cancer is the uncontrolled growth of cells. As any other cellular function, growth is controlled by genes. Genes are codes within DNA. DNA is a large string like molecule comprised of four basic molecules (Adenine, Timin, Guanine, Cytosine). They are combined in a chain like formation so that a part of a large DNA molecule may look like ..ATTACG..., where letters stand for the four basic molecules of the DNA. Entire DNA is divided into 46 smaller sub strings called chromosomes. Sub-substring of chromosomes are called genes. They control all cellular functions.

Every normal cell in our body has all genes, because all cells became from the one cell - fertilized egg (called zygote). However, not all genes are active in all cells. Certain genes are deactivated in certain cells, if they control functions not required by the specific cell.

Also, some genes are only active during certain periods of cellular life. These genes control cellular growth and multiplication. If they are hyperactive, cell will divide uncontrolled. Some genes have the ability to suppress the activity of other genes. If these genes are deactivated, cell will also divide uncontrolled.

Genes can be deactivated if the DNA molecule is damaged at the very location of the gene. This can be caused by the radiation or some substances called carcinogens. Damaged DNA will be repaired in normal cells, unless the damage is too big, but if this mechanism is damaged too, the repair will not be successful. Certain genes can be introduced into human cells, usually by viruses. This genes can then cause cellular growth. This is thought to be the mechanism of cervical cancer formation, where the Human Papiloma Virus (HPV) act as a carrier of some genes (oncogenes) and inserts them into human cells.

Etiology & Pathogenesis or How does the cancer become?
Go to the beginning

It is considered today that high levels of female sex hormone estrogen may lead to an increase in mass and number of the uterine lining cells if there is not enough progesterone, another important sex hormone in women.

In normal menstrual cycles, which are 28 days long in average, there are two phases: in the first 2 weeks estrogen is predominant sex hormone and it causes the cells of the lining to grow and increase in number. Next 14 days or so, the predominant sex hormone is progesterone. It causes cells to mature, so that the uterine lining can accept and nourish the fertilized egg.

However, if there is not enough progesterone, cells of the uterine lining (the epithelium) will simply grow and multiply more and more. That is called hyperplasia simplex - a simple growth. If that situation goes on, new glands in the lining will be formed. That is called hyperplasia complex - a complex form of growth. Finally, if cells become atypical, showing some strange behavior, then we talk about atypical growth. So there are:
- hyperplasia simplex
- hyperplasia complex
- hyperplasia simplex atypica
- hyperplasia complex atypica

High estrogen levels without enough progesterone can be found in some diseases or conditions like: long term anovulation, obesity, excessive long term estrogen intake or tumors producing estrogen, thyroid malfunctions and liver diseases.

Spreading of EC
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EC may grow on the surface of the lining, filling the uterine void, or may invade the muscular layer of the uterus, which depends on how well differentiated EC is. Less differentiated ECs have less characteristics of the normal lining cells and therefore do not behave like ones.

EC also spreads through the lymphatic and venous blood vessels. Former are thin vessels filled with lymph (see-through liquid), and the latter contain venous blood. Cells of the carcinoma get detached from the main mass and are taken by the flow to other organs and parts of the body. Such metastases may invade ovaries, or vagina (especially in the lower third). The latter may be the first sign of EC and thereby indicate further action.

EC can spread to other organs like liver, lungs, brain or bones. Such metastases can be removed surgically if they are single. However, occurrences of such metastases worsen the prognosis.

Grading and staging
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Grade is a degree of differentiation. Normal cells have genetic instructions to multiply with certain speed and to interact with other cells in a certain way. Cancer cells do not behave like normal ones and therefore they are less differentiated. Well differentiated cells that look and behave almost like normal cells are called well differentiated.

If a tumor consists of glandular formations, with less than 5% solid parts it is called Grade I. Grade III consists of more than 50% solid parts, and Grade II lies in between. Normal endometrial lining consists of glandular formations that secrete mucous like substance that nourishes fertilized egg before implantation.

Stage determines how far has EC extended locally. Adjacent organs like urinary bladder or intestines may also be affected later on. At the beginning of illness, EC consists of cells located in the lining. As tumor grows, it affects the muscular layer of the uterus and then the cervix, vagina and other organs and tissues.

Stage 1:
1a - tumor is restricted to endometrium (uterine lining).
1b - it affects less than one half of the muscular layer thickness.
1c - it affects more than one half of the muscular layer thickness.
Stage 2:
2a - tumor has invaded cervical mucosa.
2b - cervical tissue is affected.
Stage 3:
3a - uterine serosa is affected and/or adnexa (tubes and ovaries) or there are tumor cells found in the abdomen.
3b - tumor expanded to vagina, upper two thirds.
3c - lymphatic nodes are affected, especially paraaortal or pelvic.
Stage 4:
4a - urinary bladder and/or intestines (rectum) are affected.
4b - abdominal or inguinal lymphatic nodes are affected.

Stage 1aStage 1bStage 1c

Stage 2aStage 2b

Stage 3aStage 3bStage 3c

Mario Kopljar, MD
Department of Surgery
University Hospital Sestre milosrdnice
Vinogradska 29
10000 Zagreb, Croatia

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