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Cancer Pathophysiology 1

Biology of Cancer Marge Ramsdell RN, MN, OCN

Madigan Army Medical Center

Objectives

• Participants will be able to describe four differences between cancer cells and normal cells.

• Participants will be able to identify 3 terms in a pathology report which would indicate an aggressive neoplasm.

Objectives

• Participants will be able to describe 3 conditions which must be met for cancer to metastasize.

• Participants will be able to explain the overall principles of the TNM staging system.

DEFINITION: CANCER

•A large group of diseases characterized by

•cells growing out of control

•Spread throughout the body

•Malignant cell have been altered genetically to look and function differently than normal cells

•Disease of the cell and involves

•Mutations/changes in genetic makeup or DNA of the cell

Eggert, J., “ Biology of Cancer “ in Eggert J. ed. (2010) Cancer Basics.

ONS Cancer Basics Online Education Series, accessed 1/2013

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Cancer Pathophysiology 2

The Cell Cycle

Donovan, J., et. al., “Cell Prolifertion and Tumor Growth”

in Tannock, I., et. al., eds. (2005) The Basic Science of Oncology.

Regulation of the Cell Cycle

• Cyclins D, E, A, B – Cyclin-dependent kinase

(CDK) • Major control switches

• Inhibitors – p53, p21, p27, p57

• Restriction point

– G1 – Cell commited to progress

throught cell cycle

ONS Cancer Basics Online Education Series, accessed 1/2013

CHARACTERISTICS OF CANCER

Differences between Malignant Cells

and Normal Cells • Normal Cells

– Controlled growth and division

– Contact Inhibition

– Anchorage dependent

– Noninvasive

– Not immortal

• Cancer cells

– Self sufficient in growth signals

– Insensitivity to anti-growth signals

– Tissue invasion and metastasis

– Limitless replication

– Sustained angiogenesis

– Evade apoptosis

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Cancer Pathophysiology 3

So what causes Cancer?

• Age

• Hereditary factors

• Lifestyle choices (tobacco/alcohol use and diet)

• Occupational hazards (asbestos, chemicals, metals)

• Environmental exposure (radiation, sun and viruses)

• Combination of factors

Eggert, J., “ Biology of Cancer “ in Eggert J. ed. (2010) Cancer Basics.

Theories of Cancer development

• Multistep – Initiation, promotion, progress

• Mutagenesis – Changes in genetic information

• Epigenetics – Altered expression of genetic information at the

transcriptional, translational and posttranslational level

• Oncogene hypothesis – Mutations to oncogenes - overactivity

Merkle, C. J., “Biology of Cancer” in Yarbro, C.H., et. al. eds. (2011) Cancer Nursing Principles and

Practice

Theories of Cancer development

• Tumor suppressor gene – Loss or inactivity can lead to cancer

• Knudson’s “two hit” – Two mutations are needed to cause tumor formation

• Cancer stem cell hypothesis – Cancer cell that have characteristics assoc. with normal

stem cell

• Immunosurveillance – Effector cells andmediators - ID and remove cancer

cells

Merkle, C. J., “Biology of Cancer” in Yarbro, C.H., et. al. eds. (2011) Cancer Nursing Principles and

Practice

Carcinogenesis

• The process by which cancer arises – Initiation

• Carcinogens damage DNA

– Promotion

• Alter genetic structure or inhibit apoptosis

– Progression

• Invasion, angiogenesis

– Metastasis

Volker, D. L., “Biology of Cancer and Carcinogenesis” in Itano, J. K., et. al.,

eds. (2005) “Core Curriculum for Oncology Nursing

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Cancer Pathophysiology 4

Genetic influences associated with cancer

Genetic Mutations

• Proto-Oncogenes – regulate normal cell growth and repair – Oncogenes

• K-Ras

• Tumor suppressor genes – slow down cell division – P53

• Apoptosis – programmed cell death “cell suicide”

Genetic Mutations

• Somatic mutations

– Multifactorial

– Majority of cancers

• Germline mutations – Inherited/familial

– Minority of cancer

Check on Learning

Which type of mutation is present in the majority of cancers?

a. Point mutations

b. Germline mutations

c. Frameshift mutations

d. Somatic mutations

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Cancer Pathophysiology 5

Angiogenesis

•Growth of new blood vessels •Normal in embryo •Quiet in adults in most tissues

Angiogenesis

• Modualted by a number of factors:

– Vascular Endothelial

Growth Factor (VEGF)

– Fibroblast Growth Factor

– Epidermal Growth Factor

Volker, D. L., “Biology of Cancer and Carcinogenesis” in Itano, J. K., et. al., eds.

(2005) “Core Curriculum for Oncology Nursing

The Metastatic Process

•The spread of tumor cells

•Blood or lymph system

•Direct invasion

•Serosal seeding

The Metastatic Process

• Overall most common sites of metastasis:

–Lungs

–Liver

–Bone

–Lymph nodes

–Brain

Khokha, R., Voura, E., & Hill, “Tumor Progression and Metastasis”

in Tannock, I., et. al., eds. (2005) The Basic Science of Oncology.

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Cancer Pathophysiology 6

The Metastatic Process

• Detachment

• Invasion

• Survival

• Arrest

• Establishment of secondary tumor

Merkle, C. J., “Biology of Cancer” in Yarbro, C.H., et. al. eds. (2011) Cancer Nursing

Principles and Practice

Check on Learning

Which of the following is among the most common sites of metastasis?

a. Kidney

b. Lung

c. Ovary

d. Spleen

Tumor Classification

Naming Cancer

• Benign tumors are identified by the suffix “oma”

– Fibroma

• Malignant tumors usually named using

– Carcinoma, Sarcoma, or Blastoma

– Hematologic – originate from cells of blood components

• There are exceptions to the rule

– Melanoma, seminoma

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Cancer Pathophysiology 7

Naming Cancer

• Histological cell type

– Adenocarcinoma, squamous cell carcinoma

• Name of the Researcher

– Burkett’s Lymphoma

• Appearance of the cancer

– Small cell, hairy cell

• Underlying cell type

Eggert, J., “ Staging and Performance Status“ in Eggert J. ed. (2010) Cancer Basics.

Naming Cancer – Solid Tumors

Classification Tissue of Origin Prefix or name

Carcinoma

Sarcoma

Epithelial Tissue

Glandular epithelium Squamous epithelium

Connective Tissue

Bone Cartilage Fat Skeletal muscle Smooth muscle

Adeno- Squamous Osteo- Chondro- Lipo- Rhabdo- Leiomyo-

Naming Cancer – Hematologic

Classification Tissue of Origin Prefix or name

Hematologic

Leukemia Lymphoma Multiple myeloma

Blood Components

Hematopoietic cells

Lymphoid origin

Myeloid origin Lymphocytes

Plasma cells

Lympho –

Myelo – Hodgkin

Non-Hodgkin

cancer Diagnosis and

Staging

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Cancer Pathophysiology 8

Case Study

• Well to moderately differentiated adenocarcinoma

• Tumor dimension 4 CM

• Invades through the muscularis propria and into the subserosa

• Proximal and distal margins negative for tumor

Case Study

• 5/9 regional lymph nodes positive for metastasis

• Lymphovascular invasion present

• Distant metastasis to bilateral ovaries and uterus present

• Pathological staging – Stage IV (T3N2M1)

Pathologic Diagnosis of Cancer

• Pathologist is key in determining extent of cancer – Identifies and grades biopsy

– Examine sentinel lymph nodes

– Examine regional lymph nodes

– Examine tissue from distant sites

Pathologic Diagnosis of Cancer

• Mitotic activity

– Presence of dividing cells

• Pleomorphism

– Variation in size and shape of cells

• Hyperchromatism

– Nucleoli that stain darker than normal

• Abnormal chromosome arrangements

– Aneuploidy

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Cancer Pathophysiology 9

Tumor Grade and Differentiation

• Degree to which tumor cells resemble parent tissue

• Classified as Grade I, II, III, IV

– Grade 1 – Well differentiated – Low Grade

– Grade 2 – Moderately differentiated

– Grade 3 – Poorly differentiated

– Grade 4 – Undifferentiated – High grade

Tumor Grade

• Internationally developed grading systems

– Gleason

– Scarff-Bloom-Richardson (Nottingham)

• Uses more specific and objective criteria based on

– Nuclear grade may be assigned

– Mitotic count

TNM Staging Classification

• Classifies and groups cancers primarily by

– Extent of the original (primary) tumor

– Status of regional draining lymph nodes

– Presence or absence of distant metastasis

• A shorthand notation for describing the clinical and pathologic anatomic extent of a tumor.

Why is this important?

• Aids clinicians in planning a patients treatment

• Provides prognostic information

• Evaluates the results of treatment

• Facilitates the exchange of information between treatment centers

• Contributing to and advancing research on cancer

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Cancer Pathophysiology 10

Staging Classification

• Many staging systems exist – Jewett – Bladder

– Duke’s – Colorectal

– International Federation of Gynecology and Obstetrics (FIGO) – Gynecologic Cancers

• Tumor – Node – Metastasis (TNM) – Common language of solid cancers

– Utilized worldwide

TNM Staging System

• T = extent of the primary tumor

• N = presence or absence of regional lymph node metastasis

• M = presence or absence of distant metastasis

TNM System

• Primary Tumor (T) – TX – Primary tumor cannot be evaluated

– T0 – No evidence of primary tumor

– Tis – Carcinoma in situ

– T1, T2, T3, T4, - Size and/or extent of the primary tumor

• The size and extent of spread are specifically defined for each cancer site

AJCC Cancer Staging Manual, 7th Ed, 2010

TNM System

• Regional Lymph Nodes (N) – NX – Regional lymph nodes cannot be evaluated

– N0 – No regional lymph node involvement

– N1, N2, N3, N4, - Involvement of regional lymph nodes (number and/or extent of spread)

• Categorized by – Number of positive nodes

– Involvement of specific regional node groups

AJCC Cancer Staging Manual, 7th Ed, 2010

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Cancer Pathophysiology 11

TNM System

• Distant Metastasis (M) – M0 – No distant metastasis – M1 – Distant metastasis present

• M1a, M1b,

• To areas where cancer spreads by – Vascular channels – Lymphatic

• Beyond the “regional” nodes

AJCC Cancer Staging Manual, 7th Ed, 2010

Typical TNM Staging

AJCC Cancer Staging Manual, 7th Ed, 2010

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Cancer Pathophysiology 12

Other Classification Systems

• Colon cancer: Dukes

• Lymphoma: Ann Arbor, Working formulation, Rappaport Classification

• Leukemia: French-American-British (FAB) criteria

Yarbro, C., Goodman, M., Frogge, M. (2005) Cancer Nursing: Principles and Practice.

Check on learning

• Cancer cells tend to live longer than normal cells because cancer cells have defects in:

– a. Apoptosis

– b. Initiation

– c. Promotion

– d. Pleomorphism

Ask yourself…

• The histologic term pleomorphism refers to:

– a. An increase in the number of cells in tissue.

– b. A normal process that occurs in wound healing.

– c. Variations in cell size, shape, and organization.

– d. Replacement of one adult cell type by another adult cell type.

Check on learning

• A cancer that arises in glandular epithelial cells is termed a(n):

• a. Liposarcoma

• b. Adenocarcinoma

• c. Chondrosarcoma

• d. Sqamous cell carcinoma

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Cancer Pathophysiology 13

Check on learning

• A breast cancer of glandular epithelium is called: a. Glandular Carcinoma of the breast b. Ductal carcinoma of the breast c. Adenocarcinoma of the breast

Check on learning

• A malignancy of the smooth muscle of the uterus is called:

• a. Neuroblastoma

• b. Hemangioma

• c. Leiomyosarcoma

• d. Leiomyoma

Check on learning

• A malignancy of glandular epithelium of the lung with positive lymph nodes is called: a. Lung lymphoma b. Adenolymphoma of the lung

c. Papilloma of the lung d. Adenocarcinoma of the lung

Questions?