Cancer Biology & Epidemiology

Cancer

Cancer

Cells grow uncontrollably (can spread to become malignant) Can be:

• Genetic mutations from spontaneous events

• Heritable from family

-oma

Benign

lip-

Fatty tissue

Lipoma

Benign tumor of fatty tissue

adeno-

Gland tissue

-carcinoma

Malignant epithelial tissue

Adenocarcinoma

Malignant tumor of epithelial lining of a gland

Fibro-

Fibrous tissue

-sarcoma

Malignant connective tissue

Fibrosarcoma

Malignant tumor of fibrous tissue

Hodgkin's lymphoma

Cancer of lymph nodes/lymphatic system; malignant

Wilms' tumor

Nephroblastoma; malignant

Ewing sarcoma

Osteosarcoma; malignant

Misnomer

Cancers that do NOT reflect their pathological reality; behave differently than expected

• Melanoma; malignant, despite the -oma ending

• Hepatoma; hepatocellular carcinoma

Benign tumors cells?

• Similar to normal cells

• Differentiated

• Mitosis is fairly normal

Malignant tumor cells?

• Varied in size and shape with large nuclei

• Many undifferentiated

• Mitosis increased and atypical

Benign tumor growth?

• SLOW

• Expanding mass

• Encapsulated

Malignant tumor growth?

• RAPID

• Cells not adhesive, infiltrate tissue

• No capsule

Benign tumor spread?

• Remains localized

Malignant tumor spread?

• Invades nearby tissues or to distant sites through blood and lymph vessels

Benign tumor systemic effects?

• Rare

Malignant tumor systemic effects?

• Often present

Are benign tumors life threatening?

• Only in certain locations

Are malignant tumors life threatening?

• Yes, by tissue destruction and spread of tumors

Benign tumor characteristics

• Small

• Slow growing

• Noninvasive

• Nonmetastatic

• Well differentiated

Malignant tumor characteristics

• Large

• Rapidly growing with hemorrhage and necrosis

• Locally invasive

• Metastatic

• Poorly differentiated

Anaplasia

Loss of mature or specialized features (structural differentiation) of a cell or tissue

• Pleomorphism

• Reverts to immature form

• Abnormal nuclear morphology & mitoses

• Loss of polarity

• Loss of function

Carcinoma in situ (CIS)

Pre-invasive epithelial malignant tumors, have not broken through the basement membrane, have not invaded stroma; can be stage 1

Proto-oncogenes

Ras, Myc; Normal cellular proliferation (growth)

Oncogenes (oncoproteins)

Mutated proto-oncogenes, uncontrolled cell growth

DNA repair genes

BRCA1 & BRCA2

BRCA1 chromosome?

Chromosome 17

BRCA2 chromosome?

Chromosome 13

Apoptosis genes

BAX/BCL-2

Tumor suppressor genes

Regulate cell cycle, inhibit proliferation, stop cell division, prevent mutations

Governors

Put the "brakes" on; make sure bad things don't happen

Guardians

"Damage control", like the police- tag bad things and monitor; detect genomic changes

P53 & APC

Telomeres

Protect chromosome from folding and fusing, decrease DNA mutations, prevents immortality; have little caps that shorten with age

Telomerase

Restore and maintain telomeres, unlimited division and proliferation in cancer

• High amounts of in cancer patients, and telomeres actually get longer

Angiogenesis

Growth of new blood vessels

• Vascular endothelial growth factor (VEGF)

Warburg effect

Use of glycolysis under normal oxygen conditions, allows for rapid cell growth, activated by oncogenes and mutant tumor suppressors

Reverse Warburg effect

Tumor cells demand other cells to make extra lactate for the tumor to keep it fed, metabolically changes other cells

Chronic inflammation can cause development of?

Cancer

Hepatitis B and C viruses cancer?

Primary hepatocellular carcinoma

Epstein-Barr virus (EBV) cancer?

Burkitt's lymphoma

HIV/AIDS cancer?

Kaposi sarcoma herpesvirus (KHSV)

Human papillomavirus (HPV) cancer?

Cervical cancer

Reflux disease can cause which cancer?

Adenocarcinoma of lower esophagus

Heliobacter pylori can cause which cancer?

Gastric carcinoma

Local spread

Direct invasion of contiguous organs Ex: Cancer in lung spreads the the chest wall

Metastasis

Spread from site of origin to a distant site Ex: Cancer in lung, now spread to the liver

Route of metastases?

Lymphatics & Blood (hematogenous)

Metastasis selectivity sites?

Breast cancer --> bones Lymphomas --> spleen

Dormancy

Micrometastasis

Clinical manifestations of Cancer?

• Fatigue

• Cachexia

• Anemia

• Leukopenia

• Thrombocytopenia

• Infection

• GI manifestations

• Hair and skin changes

• Paraneoplastic syndromes *Hypermetabolism

Stage I

No metastasis

Stage II

Local invasion

Stage III

Spread to regional structures

Stage IV

Distant metastasis

T

Tumor spread (T-T3)

N

Lymph node involvement (N-N2)

M

Metastasis (M-M2)

Duke's A

Stage I, no mets, >90%

Duke's B

Stage II, local invasion, 55-85%

Duke's C

Stage III, spread regionally, 20-55%

Duke's D

Stage IV, distant metastasis, <5%

Duke's staging is used for?

Colon cancer

Low grade/grade I

Well differentiated, looks like normal tissue

Intermediate/grade II

Moderately differentiated

High grade/grade III

Poorly differentiated, disorganized, may be more aggresive

High grade/grade IV

Undifferentiated, high degree of anaplasia

Tumor markers

Substances produced by cancer cells that are found in tumor cells, in the blood, CSF, or urine

Chemotherapy

Uses drugs to kill cancer cells

Radiation therapy

Kills cancer cells or shrinks tumor size

Hormone therapy

Slows or stops cell growth (breast/prostate)

Targeted therapy

Target mechanism leading to cancer

Immunotherapy

Boosts the immune system to fight cancer

Stem cell transplant

Restores destroyed stem cells

Prevalence

Percentage affected with a disease at a given time

Incidence

Measure the number of new cases in a specific time period

Morbidity

Having a disease of a symptom of disease

Mortality

The number of deaths due to a disease

Sensitivity

Correctly identify those with a disease

Specificity

Identify those without the disease