Cancer Pathophysiology

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Aug 29, 2013... Cancer Basics. ONS Cancer Basics Online Education Series, accessed 1/2013 ... (2005) The Basic Science of Oncology. Regulation of the ...




Biology of Cancer Marge Ramsdell RN, MN, OCN Madigan Army Medical Center

• 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.

DEFINITION: CANCER 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.

•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

Cancer Pathophysiology




The Cell Cycle

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

Donovan, J., et. al., “Cell Prolifertion and Tumor Growth” in Tannock, I., et. al., eds. (2005) The Basic Science of Oncology.

ONS Cancer Basics Online Education Series, accessed 1/2013

Differences between Malignant Cells and Normal Cells • Normal Cells


Cancer Pathophysiology

– Controlled growth and division – Contact Inhibition – Anchorage dependent – Noninvasive – Not immortal

• Cancer cells – Self sufficient in growth signals – Insensitivity to antigrowth signals – Tissue invasion and metastasis – Limitless replication – Sustained angiogenesis – Evade apoptosis




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

Cancer Pathophysiology

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




Genetic Mutations

Genetic influences associated with cancer

• 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

Cancer Pathophysiology

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




Angiogenesis Angiogenesis

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

• 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 Metastatic Process

•The spread of tumor cells •Blood or lymph system •Direct invasion •Serosal seeding

• 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.

Cancer Pathophysiology




The Metastatic Process • • • • •

Detachment Invasion Survival Arrest Establishment of secondary tumor

Check on Learning Which of the following is among the most common sites of metastasis? a. Kidney b. Lung c. Ovary d. Spleen

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

Naming Cancer • Benign tumors are identified by the suffix “oma”

Tumor Classification

– 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

Cancer Pathophysiology




Naming Cancer • Histological cell type – Adenocarcinoma, squamous cell carcinoma

Naming Cancer – Solid Tumors Classification

Tissue of Origin


Epithelial Tissue

• Name of the Researcher

Glandular epithelium Squamous epithelium

– 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.

Prefix or name AdenoSquamous

Connective Tissue Bone Cartilage Fat Skeletal muscle Smooth muscle


Naming Cancer – Hematologic Classification

Tissue of Origin


Blood Components


Hematopoietic cells


Prefix or name

Lymphoid origin

Lympho –

Myeloid origin

Myelo –



cancer Diagnosis and Staging

Non-Hodgkin Multiple myeloma

Plasma cells

Cancer Pathophysiology




Case Study

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

Pathologic Diagnosis of Cancer

• 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 • Mitotic activity

• 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

– Presence of dividing cells

• Pleomorphism – Variation in size and shape of cells

• Hyperchromatism – Nucleoli that stain darker than normal

• Abnormal chromosome arrangements – Aneuploidy

Cancer Pathophysiology




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

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.

Cancer Pathophysiology

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

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




Staging Classification TNM Staging System • Many staging systems exist – Jewett – Bladder – Duke’s – Colorectal – International Federation of Gynecology and Obstetrics (FIGO) – Gynecologic Cancers

• T = extent of the primary tumor • N = presence or absence of regional lymph node metastasis • M = presence or absence of distant metastasis

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

TNM System • Primary Tumor (T)

• Regional Lymph Nodes (N)

– 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

Cancer Pathophysiology

TNM System – 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




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

Cancer Pathophysiology




Other Classification Systems • Colon cancer: Dukes • Lymphoma: Ann Arbor, Working formulation, Rappaport Classification • Leukemia: French-American-British (FAB) criteria

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

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

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.

Cancer Pathophysiology

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




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

Cancer Pathophysiology