BT – 4207 – ONCOLOGY

METASTASIS
CHAPTER 5

Fuad Hasan Fahim

BTGE, IU
 Metastasis
In metastasis, cancer cells break away from where they first formed (primary cancer), travel through
the blood or lymph system, and form new tumors (metastatic tumors) in other parts of the body. The
new metastatic tumor is the same type of cancer as the primary tumor. For example, if breast cancer
spreads to the lung, the cancer cells in the lung are breast cancer cells—not lung cancer cells.

Metastatic cancer: A metastatic cancer or metastatic tumor is one that has spreads from where it
started into a different areas of the body. Doctors may say "Your cancer has metastasized" — this
means the cancer has spread from its original site to another part of the body.

Cancer Spreads
• Growing into, Invading, normal tissue nearby normal tissue.
• Moving through the walls of nearby lymph nodes or blood vessels.
• Traveling through the lymphatic system and the bloodstream to other parts of the body.
• Stopping in small blood vessels at a distant location invading the blood vessel walls, and moving
into the surrounding tissue.
• Growing in this issue until a tiny tumor forms.
• Causing new blood vessels to grow, which creates a blood supply thal metastatic tumor to continue
growing

Common sites where Cancer sprerad:

Cancer Type Main Sites of Metastasis
Bladder Bone, liver, lung
Breast Bone, brain, liver, lung
Colon Liver, lung, peritoneum
Kidney Adrenal gland, bone, brain, liver, lung
Lung Adrenal gland, bone, brain, liver, other lung
Melanoma Bone, brain, liver, lung, skin, muscle
Ovary Liver, lung, peritoneum
Pancreas Liver, lung, peritoneum
Prostate Adrenal gland, bone, liver, lung
Rectal Liver, lung, peritoneum
Stomach Liver, lung, peritoneum
Thyroid Bone, liver, lung

Symptoms of Metastatic Cancer:

• pain and fractures, when cancer has spread to the bone
• headache, seizures, or dizziness, when cancer has spread to the brain
• shortness of breath, when cancer has spread to the lung
• jaundice or swelling in the belly, when cancer has spread to the liver

Steps of metastasis
• Spread into tissue near the original cancer site
• Invade the walls of nearby blood vessels or lymph nodes
• Follow the bloodstream and lymphatic system to distant body parts
• Invade distant small blood vessel walls and spread into the surrounding tissue
• Form a small tumor (a metastatic tumor) in that tissue
• Grow new blood vessels to supply blood to the new tumor so it grows

1|Page
Routes of metastasis
1. Hematogenous spread (via the blood)
Invasion of blood vessels allows escaped tumor cells to be transported
through the blood stream to another part of the body. Tumor penetrates
the vessel wall and grows into the:
1. The lymph channels are the first (regional) drainage area to which nodes are involved as being
remote (distant) from the primary site.
2. Tumor cells can be filtered by small capillaries or lymph nodes in the body.
2. Lymphatic spread (via lymphatic system)
Example: malignant cancers of the breast rupture the primary tumor and are released into the
surrounding connective tissue. They enter the lymphatics and begin to grow on any tissue reached by
the lymph.
3. Implantation via fluids in bodily cavities
Some tumors shed cancerous cells into body cavities so that fluid accumulates. However, the presence
of fluid does not automatically indicate dissemination. There must be cytologic evidence of malignant
cells.

Diagnosis of metastasis
i. A neurological exam:
• Checking mental status, vision, hearing, balance, coordination, and reflexes.
• The part of the nervous system affected by a brain tumor will be reflected in the patient's
symptoms.
ii. MRI and CT imaging and tests of metastatic lesions are often used.
iii. A biopsy:
• A sample of tissue is removed and examined.
• It can be performed as an open operation or it can be done by using a needle.

Treatment of metastasis
1. Medications:
• Bone-building medications
• Intravenous radiation
• Chemotherapy
• Hormone therapy
• Pain medications
• Steroids
• Targeted therapy
2. External radiation therapy:
Radiation beams, using high-powered energy such as X-rays and protons, to kill cancer cells.
3. Surgery:
• Surgery to stabilize the bone
• Surgery to inject a bone cement
• Surgery to repair a broken bone

Types of cancer are metastasize

Some of the most common types include metastatic:
• Bone cancer
• Prostate cancer • Colon cancer
• Lung cancer • Breast cancer
• Kidney cancer • Liver cancer
• Thyroid cancer

2|Page
Molecular mechanism of metastasis:

This image
visually explains
the step-by-step
process of cancer
metastasis—how
cancer spreads
from its original
site to other parts
of the body. Here's
a simple, detailed
explanation of
each step shown:
1. Primary
Tumor
Formation
• Cancer
begins
when
abnormal
cells grow uncontrollably in one place (the primary tumor).
• These cells multiply and form a mass within the original tissue.
2. Local Invasion
• The tumor grows larger and invades nearby tissues.
• Cancer cells start breaking through the boundaries of the original site.
3. Intravasation
• Cancer cells enter blood vessels (or lymphatic vessels).
• This is the first step in traveling to other parts of the body.
4. Survival in the Circulation
• Once in the bloodstream, cancer cells must survive immune attacks and mechanical forces.
• Many cells die, but some manage to stay alive while traveling through the blood.
5. Arrest at a Distant Organ Site
• Cancer cells stop or get stuck at a distant organ (like lungs, liver, or bones).
• This happens when the blood flow slows or the vessel narrows.
6. Extravasation
• The surviving cancer cells exit the blood vessel and enter the tissue of the new organ.
7. Micrometastasis Formation
• The cancer cells begin to grow again in the new tissue.
• At first, they form a tiny group of cells (micrometastasis) that is not yet detectable.
8. Metastatic Colonization
• The small cancer group grows into a larger tumor at the new site.
• The tumor establishes itself by forming new blood vessels (angiogenesis).
9. Clinically Detectable Macroscopic Metastases
• Now, the tumor is large enough to be seen in scans or tests.
• This is when metastatic cancer is usually diagnosed, as it has spread to distant organs.
Summary:
This process shows how cancer can silently travel from its origin to other body parts, making early
detection and treatment very important. The journey includes escaping the original site, surviving
in circulation, and growing in new tissues—leading to secondary tumors called metastases.

3|Page
 Breast cancer
Breast cancer originates in your breast tissue. It occurs when breast cells mutate (change) and grow
out of control, creating a mass of tissue (tumor). Like other cancers, breast cancer can invade and
grow into the tissue surrounding your breast. It can also travel to other parts of your body and form
new tumors. When this happens, it's called metastasis.

Types of Breast Cancer:

1. Infiltrating (invasive) ductal carcinoma: Breaks the wall of your duct and spreads to surrounding
breast tissue. About 80% of all cases, this is the most common type of breast cancer.
2. Ductal carcinoma in situ: Also called Stage 0 breast cancer. This condition is very treatable.
Infiltrating (invasive) lobular carcinoma: This cancer forms in the lobules of your breast (where
breast milk production takes place) and has spread to surrounding breast tissue. It accounts for
10% to 15% of breast cancers.
3. Lobular carcinoma in situ: It isn't a true cancer, but this marker can indicate the potential for breast
cancer later on.
4. Triple negative breast cancer (TNBC): Making up about 15% of all cases. It's called triple negative
because it doesn't have three of the markers associated with other types of breast cancer. This
makes prognosis and treatment difficult.
5. Inflammatory breast cancer: Rare and aggressive, this type of cancer resembles an infection.
Swelling, pitting and dimpling of their breast skin. It's caused by obstructive cancer cells in their
skin's lymph vessels.
6. Paget's disease of the breast: This cancer affects the skin of your nipple and areola (the skin around
your nipple).

Signs of breast cancer

• A change in the size, shape or contour of your breast.
• A mass or lump, which may feel as small as a pea.
• A lump or thickening in or near your breast or in your underarm that persists through your
menstrual cycle.
• A change in the look or feel of your skin on your breast or nipple (dimpled, puckered, scaly or
inflamed).
• Redness of your skin on your breast or nipple.
• An area that's distinctly different from any other area on either breast.
• A marble-like hardened area under your skin.
• A blood-stained or clear fluid discharge from your nipple.

Causes breast cancer

• Age: Being 55 or older increases your risk for breast cancer.
• Sex: Women are much more develop than men.
• Family history and genetics: About 5% to 10% of breast cancers are due to single abnormal genes
that are passed down from parents to children.
• Smoking: Tobacco use has been linked to many different types of cancer, including breast cancer.
• Alcohol use: Drinking alcohol can increase certain types of breast cancer.
• Obesity: Having obesity can increase your risk of breast cancer.
• Radiation exposure: If you've had prior radiation therapy - especially to your head, neck or chest
- you're more likely to develop breast cancer.
• Hormone replacement therapy: Hormone replacement therapy (HRT) have a higher risk of being
diagnosed with breast cancer.

4|Page
Diagnosis
• Mammogram: X-ray images can detect changes or abnormal growths in your breast. Mammogram
used in breast cancer prevention.
• Ultrasonography: This test uses sound waves to take pictures of the tissues inside the breast.
• Positron emission tomography (PET) scanning: Injects a special dye into veins and takes images
with scanner.
• MRI: Uses magnets and radio waves to produce clear images of the structures inside breast.

Stages of breast cancer

• Stage 0: The disease is non-invasive. Hasn't broken out of your breast ducts.
• Stage I: Have spread to the nearby breast tissue.
• Stage II: Can measure anywhere between 2 to 5 cm across, may or may not affect lymph nodes.
• Stage III: Has spread beyond the point of origin. Have invaded nearby tissue and lymph nodes,
but it hasn't spread to distant organs.
• Stage IV: Spread to areas away from your breast, such as your bones, liver, lungs or brain. This
cancer is called metastatic breast cancer.

Molecular mechanism of breast cancer:

5|Page
 Prostate cancer
It develops in the prostate gland, a part of the male reproductive system. It tends to grow slowly and
stay in the gland. Prostate cancer is cancer that occurs in the prostate. The prostate is a small walnut-
shaped gland in males that produces the seminal fluid that nourishes and transports sperm.
Symptoms
• Frequent, sometimes urgent, need to urinate, especially at night.
• Weak urine flow or flow that starts and stops.
• Painful urination (dysuria).
• Fecal (bowel) incontinence.
• Painful ejaculation and erectile dysfunction.
• Blood in semen (hematospermia) or urine.
• Lower back pain, hip pain and chest pain.
• Leg or feet numbness.
Stages of prostate cancer
• Assign a grade to each type of cell in your sample. Cells are graded on a scale of three (slow-
growing) to five (aggressive) are considered normal tissue.
• Adds together the two most common grades to get your Gleason score (ranging from six to 10).
• Uses the Gleason score to place you into a Grade Group ranging from one to five. A Gleason score
of six puts you in Grade
Group 1 (slow-growing
cancer that might not
require treatment). A score
of nine or higher puts you
in Grade Group five
(aggressive, faster-
growing cancer that
requires immediate
treatment). Samples with a
higher portion of more
aggressive cells receive a
higher Grade Group.
Causes prostate cancer
• Get prostate cancer if your father, brother or son has the disease.
• Inherited mutated (changed) breast cancer genes (BRCA1 and BRCA2) and other gene mutations
contribute to a small number of prostate cancers.
Diagnosis
• Digital rectal exam: Inserts a gloved, lubricated finger into the rectum and feels the prostate
gland. Bumps or hard areas could indicate cancer.
• Prostate-specific antigen (PSA) blood test: The prostate gland makes a protein called prostate-
specific antigen (PSA). Elevated PSA levels may indicate cancer.
• Biopsy: A needle biopsy to sample tissue for cancer cells is sure way to diagnose this.
Treatment
• Active surveillance: Screenings, scans and biopsies every one to three years to monitor cancer
growth.
• Watchful Waiting: Watchful waiting sounds similar to active surveillance, but is often used in
older or frailer patients.
• Brachytherapy: Internal radiation therapy, involves placing radioactive seeds within the prostate.
• External beam radiation therapy: With external beam radiation therapy, a machine delivers strong
X-ray beams directly to the tumor.
6|Page
• Systemic therapies: These therapies include chemotherapy, androgen deprivation hormone
therapy and immunotherapy.
• Focal therapy: Focal therapy options include high-intensity focused ultrasound (HIFU),
cryotherapy, laser ablation and photodynamic therapy.
• Prostatectomy: Removes the diseased prostate gland. Surgeons can perform laparoscopic
prostatectomy and robotic.

Molecular mechanism of prostate cancer

Cellular progression of prostate cancer. Prostate cancer originates from the luminal or basal cells of
the normal prostate epithelium. At first, premalignant lesions, referred as prostatic intraepithelial
neoplasia (PIN) develop. Only the high-grade PIN (HGPIN) transform into malignant invasive
prostate adenocarcinoma and eventually progress to become a metastatic disease spreading to the
lymph nodes, bone, liver, and lung via the circulation system. Different molecular alterations have
been reported in different stages of prostate cancer progression. In HGPIN, an overexpression of
BCL2, GSTP1, MYC and a loss of PTEN, NKX3.1, TMPRSS2-ERG fusion and SPOP mutation are
reported. In early stage prostate carcinoma, a loss of tumor suppressor genes such as PTEN and RB1
and overexpression of certain oncogenes with frequent mutations such as FOXA1 have been reported.
During progression to metastatic stage, multiple molecular alterations such as overexpression and/or
mutations in AR, ATM, ATR, RAD51, and CXCR4, and loss of various tumor suppressors such as
SMAD4 has been reported.

Gleason score: The Gleason score is very important in predicting the behavior of a prostate cancer
and determining the best treatment options. Still, other factors are also important, such as: The blood
PSA level. Findings on rectal exam
The Gleason grading system refers to how abnormal your prostate cancer cells look and how likely
the cancer is to advance and spread. A lower Gleason grade means that the cancer is slower growing
and not aggressive.

7|Page
 Lung cancer
Lung cancer is cancer that forms in tissues of the lung, usually in the cells that line the air passages.
It is the leading cause of cancer death in both men and women. There are two main types: small cell
lung cancer and non-small cell lung cancer. It develops when normal processes of cell division and
growth are disrupted, giving way to abnormal, uncontrollable growth. The cells grow into a mass or
tumor.
Types:
1. Non-small cell lung cancer: It is much more common, and grows and spreads more slowly.
➢ Adenocarcinoma: Growing near the periphery of the lung and may vary in both size and growth
rate.
➢ Squamous cell carcinoma: starts in one of the larger breathing tubes near the center of the
chest.
➢ Large cell carcinoma: starts near the periphery of the lung, grows rapidly.
2. Small cell lung cancer: It is less common than type 1, about 15% of all lung cancers. It grows
rapidly.
Symptoms
• Coughing. Hoarseness. Blood that is expelled by coughing. Weakness. Wheezing. Infections.
Chest pain.
Prevent lung cancer
• Do not smoke. • Substances containing nickel or chromium,
• Reduce chemicals such as: • Coal products, Air pollution,
• Arsenic, • Radon (a radioactive gas that has no color or odor.)
• Asbestos, • Eat a healthy diet.
• Beryllium, • Exercise regularly.
• Cadmium,
Treatment: People with non-small cell lung cancer can be treated with surgery, chemotherapy,
radiation therapy, targeted therapy, or a combination of these treatments. People with small cell lung
cancer are usually treated with radiation therapy and chemotherapy. Surgery. An operation where
doctors cut out cancer tissue.
Molecular mechanism:

8|Page
 Liver cancer
A cancer that's found anywhere in the liver. Liver cancer can sometimes start in your liver (primary)
or spread from another organ (secondary).

Liver cancer affect my body:

• Collects and filters blood flowing from your intestines.
• Processes and stores nutrients that your intestines absorb.
• Changes some nutrients into energy or substances that your body needs to build tissue.
• Makes bile, a fluid that helps digest fat.
• Digests and stores other nutrients from food like sugar which makes energy.
• Makes substances that help your blood to clot.

Stages of liver cancer:

• Stage I/very early stage/stage 0: A single tumor in liver that measures less than 2 cm. Blood tests
show your bilirubin level is normal.
• Stage II/early stage/stage A: A single tumor that measures 5 cm or less or you have more than one
tumor that measures less than 3 cm. The tumor may have spread to your blood vessels.
• Stage III/intermediate stage/stage B: Have more than one tumor measures more than 5 cm. Spread
to lymph nodes, large blood vessels or another organ.
• Stage IV/advanced stage/stage C: Spread to other places in body, such as lungs or bones, as well
as lymph nodes.

Diagnosis of liver cancer:

• Blood tests: Test for alfa-fetoprotein (AFP). High AFP levels may indicate liver cancer.
• Ultrasound (sonography): Ultrasound to look for liver tumors.
• CT scan: X-ray takes detailed images of liver, providing information about liver tumor size and
location.
• MRI: This test produces very clear images of your body using a large magnet, radio waves and a
computer.
• Angiogram: Examine liver's blood vessels. Injects dye into an artery can track blood vessel activity
and look for blockages.
• Biopsy: Biopsies are the most reliable way to confirm a liver cancer diagnosis.

Prevent of liver cancer:

• Avoid behaviors that lead to cirrhosis.
• Reach or maintain a healthy weight.
• Get a hepatitis B vaccine. This vaccine is safe for nearly everyone. Ask your doctor about the
hepatitis A vaccine.
• Avoid hepatitis C.
• If you have any liver disease, have diabetes, obesity or are a heavy drinker, ask your healthcare
provider about liver cancer screenings.

9|Page
Molecular mechanism of liver cancer:

10 | P a g e