patho final winter 26

what is cancer

uncontrolled growth of abnormal cells in the body

malignant meaning

cancerous cells

what is the composition of cancerous cells

• less well differentiated

• have lost the ability to control cell proliferation and differentiation into mature cells

what is oncology

the study of tumours and their treatment

• includes non-malignant

what is the most common cancer in men

prostate

what is the most common cancer in women

breast

what cancer has the leading cause of death

• lung (1/2)

• colorectal and breast

what are the 5 phases in the cell cycle

• G zero, G1, S (synthesis), G2, M (mitosis)

what is the complete cell cycle

• cell duplicates content and divides into 2 identical daughter cells

what occurs during the synthesis phase

• DNA synthesized and chromosomes are replicated

what happens during the mitosis phase

• cell divides and 2 daughter cells are formed

what happens during the G phase

• cell is metabolically active  or growing enzymes or proteins in preparation for DNA synthesis or mitotic division

what is G zero

dormancy state

what is cell proliferation

cells duplicating and increasing in number

what is cell differentiation

process by which proliferating cells become specialized

what are the 3 categories of cell differentiation and proliferation

• cells that never or rarely divide (nerve, skeletal, cardiac)

• cells that continue to proliferate and then die, particularly in areas that have high cell turnover (ex. GI tract, skin, and blood cells → progenitor cells)

• Stem cells which can enter the cell cycle and produce progenitor cells when required

what is allogenic stem cell transplant

receive donors stem cells

what is autologous stem cell transplant

receive own stem cells

• done after diseased bone marrow is destroyed via chemo and radiation

how do cancer cell complete the cell cycle more quickly

• reduce G1

• less likely to enter G zero

what are checkpoints during the cell cycle

series of processes and proteins that help regulate cell damage and repair including apoptosis

• G1-S checkpoint: monitors if DNA in chromosomes is damaged by radiation or chemicals

• Ex. G2-M checkpoint (most important): prevents entry into mitosis if DNA replication is not complete

what is carcinogenesis

the process by which normal cells are transformed into cancer cells

what causes carcinogenesis

mutation of the genetic material of normal cells, which upsets the normal balance between proliferation and cell death

how many cell divisions can cancerous cells undergo

infinite

what are the 3 stages of carcinogenesis

initiation, promotion, progression

what is initiation in carcinogenesis

• Exposure of cells to carcinogenic agent that makes susceptible to malignant transformation

what are agents in initiation of carcinogenesis

• Agents produce irreversible changes in genome of cell

  • chemical, physical, biological

what is the promotion phase of carcinogenesis

• Dysplasia: unregulated and accelerated growth of the mutated cells 

  • Indicative of an early neoplastic process

what is the progression phase of carcinogenesis

The process whereby tumor cells acquire malignant changes and autonomous growth tendencies that promote invasiveness and metastatic capabilities

what is carcinoma in situ

•  “cancer in place” → represents transformation of neoplastic lesion to one in which cells undergo essentially no maturation, and this may be considered cancer like

  • abnormal cells are found only in their original location—the epithelium—and have not spread to surrounding tissues

    • Remains localized and no invasion of basement membrane

what is invasive carcinoma

• cancer has invaded beyond basement membrane and has potential to metastasize or spread to other parts of body

what are the 4 bases of dna

• adenine, thymine, cytosine, guanine

what are proto-oncogenes

encourage cell division

• Mutated: activated and become oncogenes (stimulate excessive division)

what are tumor suppressor genes

• inhibit cell division

  • Mutated: inactivate genes, eliminating critical inhibition of cell division that normally prevents excessive growth

what do proto-oncogenes and tumor suppressor genes do together

• coordinate regulated growth that normally ensures that each tissue and organ in body maintains size and structure that meets body’s needs

how do oncogenes cause cancer

• instructing cells to make proteins or “go signals” that stimulate excessive cell growth and division

• Results in growth signaling pathway to become hyperactive

• More active pathway= faster growth and division

• Cancer cell may contain one or more oncogenes

• not inherited

how do tumour suppressor genes cause cancer

When not functioning correctly cells with DNA damage continue to divide and can accumulate further DNA damage that eventually leads cell to grow and divide in uncontrolled fashion

• inherited (two copies - from each parent)

what is the dna repair system

• instructs cell to repair damaged DNA in virtually every cell

what happens over time as cells are being attacked by chemicals and carcinogens

• Results in mutations in many different ways

  • Single base (simplest), more than one base

  • Large segments of DNA repeated, deleted, or moved

  • Errors during replication

  • *usually corrected by DNA repair system but if system is mutated subsequent mutations occur and become a permanent feature

what is xeroderma pigmentosum

• inherited defect in a DNA repair system

  • Result: cannot repair DNA damage that normally occurs when skin cells are exposed to sunlight so exhibit abnormally high incidence of skin cancer

what is mismatch repair

• DNA polymerase copies both strands of DNA (top and bottom= Watson and Crick)

  • Sometimes DNA polymerase incorporates the wrong nucleotide (A and C + T and G)

what are repair proteins

• MSH2, MSH6, MLH1, PMS2

  • These recruit another enzymes called EXO1 (exonuclease that chops off the mutant strand) and then allows DNA polymerase to come by and synthesize the correct strand to fix and make normal

what is apoptosis

Balances generation of new cells via division and death

old cells become damaged over time and are eliminated

how does tumor suppressor genes impact apoptosis

tumor suppressor genes can stimulate cells with damage DNA to commit cell suicide

• Tumor suppressor p53: in normal cells that have DNA damage initiates cell suicide that prevent genetic damage from growing out of control

  • Abnormalities cause damaged cells to continue to grow and divide

  • Found in over 50% of human cancers (lung, colorectal, breast)

  • Most frequently mutated gene in human cancer

what is the first and last defence against cancer

immune system

what are NK cells

• target tumors and cancer cells to kill them

what is metastasis

• The spread of cancer from its original location to other parts of the body

how does metastasis occur

• 1: malignant cells can directly invade or extend into adjacent organs or sites

• 2: individual cancer cells move away from primary tumor and enter blood or lymph circulation then travel and get stuck in capillary bed os distant organ or site, then grow until they burst through capillary wall

what are the most common sites of metastasis

lungs, bones, liver

what is angiogenesis

process of forming new blood vessels

• Growth of new network of blood vessels is required for cancer metastasis

how does cancer promote angiogenesis

when tumor becomes large enough to need increased nutrients and oxygen supply, hypoxia triggers tumor and surrounding environment to release signals that result in growth of blood vessels towards and into the tumor

what is tumor angiogenesis

•  the proliferation of a network of blood vessels that penetrates into cancerous growths, supplying nutrients and oxygen and removing waste products

what are angiogenesis inhibitors

• One class of angiogenesis inhibitors: molecules directly inhibit growth of endothelial cells

  • Endostatin: naturally occurring protein known to inhibit tumor growth in animals

  • Thalidomine: has ability to prevent endothelial cells from forming new blood vessels

• Second group: molecules that interfere with steps in the angiogenesis signaling cascade

  • Bevacizumab (avastin): proven to delay tumor growth and extend lives of patients

  • Interferon-alpha: naturally occurring protein that inhibits production of growth factors from starting the angiogenesis signaling cascade

what are the characteristics of cancer cells

what is the etiology of cancer

• 5-10% inherited (so not considered inherited illness)

• Identify at risk individuals

• DNA testing

• Family history

• BRCA1 or BRCA2 mutations

• Potentially life saving interventions aimed to reducing risk

  • Ex. tamoxifen for breast cancer, colonoscopy for colon cancer, risk reducing salpino-oophorectomy for ovarian cancer

what are BRCA1 and BRCA2 mutations

• Women who have these susceptibility genes have 80% chance of developing breast cancer by the age of 65

• Not having genes does not exempt you from risk (can be due to genetic changes)

how is age a cancer risk factor

• more time available to accumulate mutations

• Leading risk factor for developing cancer: advanced aging

how to screen for cancer regarding age

• PSA (prostate specific antigen) testing

• Fecal immunochemical test

• colonoscopy

• mammogram

• clinical breast exam

• pap smear

who are at high risk of prostate cancer

• black men

• family history

what is prostate specific testing criteria

• Prostate cancer rarely screened before 40 and risk doubles each decade after 40

• Canadian Cancer Society recommends men at average risk of prostate cancer consider PSA from age 50]high risk : age 45

what is fecal immunological test (FIT) criteria

• Beginning at age 50 both men and women at average risk should have stool testing every 2 years

• Test uses antibodies to detect presence of blood in stool which can indicate polyps (pre cancerous lesion) or colorectal cancer

colonoscopy criteria

• Those at increased risk for colorectal cancer should be screened every 5 years or every 10 years beginning at 50

• OR 10 years earlier than the age at which a first degree relative was diagnosed with colorectal cancer

  • Every 5 years if relative was diagnosed before 60

  • Every 10 years if diagnosed after age 60

mammogram criteria

• Average risk 50-74: every 3 years

• High risk 30-69: annually with both mammography and MRI

who is considered high risk for a mammogram

• person with a known gene mutation that increases risk for breast cancer,

• first degree relative of someone with a gene mutation,

• is assessed as having a 25% or greater lifetime risk of breast cancer based on personal family history,

• has had radiation therapy of the chest to treat another cancer or condition

clinical breast exam criteria

• physical exam of breasts conducted by physician to check for signs of cancer

pap smear criteria

Sexually active women should have to screen for cervical cancer from age of 21 every 1-3 years depending on previous results

what are environmental carcinogens

• UV light

  • From natural sunlight, sunlamps, or tanning beds

  • Can lead to melanoma and other forms of skin cancer

• Radiation

  • Via Hiroshima or ionizing radiation (CT scans)

• Chemical

  • Benzene, asbestos, smoke

• Bacteria

  • Helicobacter pylori bacteria causes stomach ulcers and leads to stomach cancer

• Viruses

  • Cervical cancer, liver cancer, some lymphomas, leukemias, sarcomas

  • Ex. HPV causes cervical cancer

  • Ex. Epstein Barr virus → Burkitt's Lymphoma

  • Ex. Hepatitis B → liver cancer

  • Ex. HIV → Kaposi’s sarcoma

what are lifestyle risk factors for cancer

• alcoholic drinks

• tobacco

• obesity

  • ⅓ breast cancer from failure to limit adult weight gain

  • Link between obesity and cancer of gallbladder, ovaries, pancreas

• diet

  • (poor or high in fat) Increased risk of colon, uterus, and prostate cancer

• hormones

• stress + sleep deprivation

how are hormones a risk factor for cancer

• Menopausal hormone therapy (estrogen) increases risk of breast cancer, heart attack, stroke, blood clots

• Fluctuating hormone levels are related to cancers such as breast and uterine cancer

what is neoplastic

• abnormal growth of new tissue

what is tumour

• used interchangeably with neoplastic growth

  • Benign: non cancerous tumor

  • Malignant: cancerous tumor cell growth

what is neoplastic nomenclature

• way of describing tumor growth that is benign or malignant

what are characteristics of benign tumours

• Well differentiated

• Slow growing

  • May even regress eventually

• Look like tissues from which they arise

• localized

• encapsulated

• can interfere with vital functions

  • Pressure on tissues, blood vessels, or nerves, however, usually do not cause death unless interfere with vital functions because of location

  • Some benign are known for ability to cause alterations in body function by abnormally producing hormones

what is suffix oma meaning

tumor growth or mass

• added to tissue type

  • lymphoma or lymphosarcoma

what are epithelial gland tissue benign tumours called

adenoma

thyroid adenoma characteristics

• The typical single node separates it from a multinodal goiter

• Most do not cause symptoms (known as warm or cold adenomas)

• Symptoms: hyperthyroidism: excessive sweating, nervousness, agitation, rapid heart rate, weight loss, fatigue (if show symptoms known as hot adenomas)

pituitary adenomas characteristics

• From epithelial tissue of pituitary gland

• Can cause too much prolactin secretion which can trigger breast milk production in non lactating females and males and amenorrhea

• May also produce excess growth hormone after the growth plates have closed causing acromegaly (enlargement of the “acrals” or small bones and enlargement of soft tissue

fibroadenomas characteristics

• Made of fibrous and glandular tissue in the breast

• May consider biopsy because presents same as breast cancer

  • Differs from breast cancer because easy to move with clearly defined edges

colon adenomas characteristics

• On surface of colon (called a polyp) ← how colorectal cancer begins

• 2 most common types of intestinal polyps: adenomas and hyperplastic polyps

• Develop when there are errors in the way cells grow and repair the lining of the colon

what are connective tissue benign tumours called

fibromas

lipoma

osteoma

fibromas characteristics

skin tags

• Increase in frequency with age

• More common is obese persons possibly due to skin irritation and rubbing of skin folds

• Skin tags like bumps that bleed, grow, or display multiple colours can require biopsy to exclude other causes like skin cancer

lipoma characteristics

• Made of connective adipose tissue

• Most common form of soft tissue tumor

• Soft to touch, usually moveable, and are generally painless

• Vary largely in size

• More common in adults 40-60 but can be in children too

osteoma characteristics

• New piece of bone usually growing on another piece of bone, typically the skull

• Most common benign neoplasm of the nose and paranasal sinuses

• Larger ones may cause facial pain, headache, infection

what are muscle tissue benign tumours called

leiomyoma

rhabdomyoma

leiomyoma characteristics

• Uterine muscle (aka uterine fibroids)

• common over 30

• cause may be related to estrogen

• Fibroids will grow as long as woman is menstruating

• Symptoms: abdominal fullness, gas, constipation, bleeding between periods, increase in urinary frequency, heavy menstrual bleeding or menorrhagia, menstrual periods lasting longer than normal, pelvic cramping/pain with periods, sensation of fullness or pressure in the abdomen

rhabdomyoma characteristics

• Tumor of striated muscle

• Most commonly associated with tongue and heart but also other locations

what are neural tissue benign tumours called

neuroma

glioma

meningioma

neuroma characteristics

• Tumor of nerve tissue

• Can be applied to any swelling of a nerve

glioma characteristics

• Starts in brain or spine

• Arises from glial cells

• Most common site: brain

meningioma characteristics

• Tumor of meninges (layer of tissue covering brain and spinal cord)

• Compress adjacent brain tissues with growth

• Symptoms: related to compression of brain tissue which can also affect cranial nerves and blood vessels

• Growth can extend into bones and head and face and produce visible changes

• Some of these tumors can cause disabilities and may sometimes be life threatening

endothelial tissues benign tumours names

hemangioma

lymphangioma

hemangioma characteristics

• Tumor of the cells that line blood vessels

•  Connected to circulatory system and filled with blood

• On surface of skin: look like ripe strawberry

• Under skin: bluish swelling

• Sometimes grow in internal organs like liver or larynx

• Sometimes present as flat red or pink area

• Most common childhood tumor (around 10% of caucasians)

lymphangioma characteristics

• Malformations or cell growth of lymphatic system

• Can occur at any age and may involve any part of the body

• 90% occur in children less than 2 years old and involve head and neck

• Usually treated for cosmetic reasons only

malignant tumour characteristics

• Less well differentiated/anaplasia (lost control of differentiation in cancerous tissues)

• Do not resemble originating tissues

• Rapid, disorganized growth patterns

• Not encapsulated: invade local tissues, organs or blood vessels

• Rob normal tissues of essential nutrients

  • Release enzymes , toxins, and hormones called cytokines that destroy normal tissue

• Metastasize through blood and lymph

• Add suffix “carcinoma” or “sarcoma” to the tissue type

poorly differentiated meaning

poorly resembles the cell that it arose from

• Undifferentiated: malignant cells are immature, embryonic in nature and there is no resemblance to the cell from which they arose

epithelial gland malignant tumour characteristics

tissue that covers and lines the body

• *most common cancer

  • Squamous cell carcinoma (surface epithelial)

    • Skin and lining of esophagus and rectum

  • Adenocarcinoma (internal body organ)

    • Adenomatous cells

    • Ex. pancreas, lung

connective tissue malignant tumour characteristics

supporting tissue of the body (bones, cartilage, tendons, fibrous tissue that supports organs)

• *cancers are called sarcomas

• 2 types: bones sarcomas and soft tissue sarcoma

  • Fibrosarcoma

  • Liposarcoma

  • Osteosarcoma

  • Lymphosarcoma

muscle tissue malignant tumour locations

• smooth muscle: found in internal organs like stomach, intestines, blood vessel, uterus (causes contractions) ← involuntary

• Skeletal muscle: sometimes called striated because stripes can be seen inside the cells under the microscope, allows us to voluntarily move

• leiomyosarcoma, rhabdomyosacrocoma

leiomyosarcoma characteristics

• Malignant tumors of smooth muscle

• Can grow almost anywhere in body

• Often in retroperitoneum (back of abdominal cavity), internal organs, and blood vessels

• Less in deep soft tissues of legs or arms

rhabdomyosarcoma characteristics

• Malignant tumors of skeletal or striated muscle

• Common in arms or legs but can also begin in head and neck area and in reproductive and urinary organs like vagina or bladder

• Children affected more than adult