Focus on Cancer: Part 1 Biology, Classification, Diagnosis

Focus on Cancer: Part 1 Biology, Classification, Diagnosis
(Relates to Chapter 16, “Cancer,” in the textbook) Focus on Cancer: Part 1 Biology, Classification, Diagnosis Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.
Cancer Group of more than 200 diseases Characterized by uncontrolled and unregulated growth of cells Occurs in people of all ethnic groups and all ages A majority of cases (77%) are diagnosed in those over the age of 55 years. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Cancer ~1,450,000 persons diagnosed with cancer in 2006 Excluding basal and squamous cell skin cancers More than 1 million cases of basal and squamous cell skin cancer annually Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Cancer Higher in men than women Incidence and death rates are higher in African Americans than in whites and other minorities. Second most common cause of death in the United States after heart disease Gender differences in incidence and in death rates for specific cancers are presented in Tables 16-1 and 16-2 and the Gender Differences box. Annually, about 566,000 Americans die as a result of cancer, which is more than 1500 people per day. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Cancer 5-Year survival rate is now 66% for those who are Disease free In remission Under treatment Does not include number of people who are “cured” of cancer More than 10 million Americans are alive today who have a history of cancer. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Defect in Cellular Proliferation
Most human tissues contain predetermined, undifferentiated stem cells. Predetermined stem cells give rise to mature cells of the type of tissue where they reside. {See next slide for figure} Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Cell Life Cycle and Metabolic Activity
Cell life cycle and metabolic activity. Generation time is the period from M phase to M phase. Cells not in the cycle but capable of division are in the resting phase (G0). Fig Cell life cycle and metabolic activity. Generation time is the period from M phase to M phase. Cells not in the cycle but capable of division are in the resting phase (G0). Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc. 8

All cells are controlled by an intracellular mechanism that determines proliferation. Cancer cells grown in culture are characterized by loss of contact inhibition. Grow on top of one another and on top of or between normal cells Under normal conditions, a state of dynamic equilibrium is constantly maintained (i.e., cellular proliferation equals cellular degeneration or death). Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Cancer cells respond differently than normal cells to intracellular signals regulating equilibrium. Divide indiscriminately Cancer cells divide indiscriminately and haphazardly. Sometimes they produce more than two cells at the time of mitosis. A common misconception regarding the characteristics of cancer cells is that the rate of proliferation is more rapid than that of any normal body cell. In most situations, cancer cells proliferate at the same rate as the normal cells of the tissue from which they originate. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Stem cell theory Loss of intracellular control of proliferation results from mutation of stem cells. DNA is substituted or permanently rearranged. The stem cells are viewed as the target or the origin of cancer development. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Once mutated Cells can die from damage or by initiating programmed cellular suicide (apoptosis). Can recognize damage and repair itself Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Once mutated (cont’d) Can survive and pass on damage to two or more daughter cells Surviving mutated cells have potential to become malignant. The stem cell theory of cancer development is not complete because malignant stem cells can differentiate to form normal tissue cells. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Normal Cellular Differentiation
Orderly process progressing from a state of immaturity to a state of maturity Stable and will not change Exact mechanism of normal cellular differentiation is not completely understood. Under normal conditions, the differentiated cell is stable and will not dedifferentiate (i.e., revert to a previous undifferentiated state). {See next slide for figure} Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Normal Cellular Differentiation
Fig Normal cellular differentiation. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Defect Cellular Differentiation
Two types of genes that can be affected by mutation are Protooncogenes Regulate normal cellular processes such as promoting growth Tumor suppressor genes Suppress growth Mutations that alter the expression of protooncogenes can activate them to function as oncogenes (tumor-inducing genes). Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Defect in Cellular Differentiation
Protooncogenes Genetic locks that keep cells functioning normally Mutations that alter their expression can activate them to function as oncogenes. When this lock is “unlocked,” as may occur through exposure to carcinogens or oncogenic viruses, genetic alterations and mutations occur. For example, some cancer cells produce new proteins, such as those characteristic of the embryonic and fetal periods of life. These proteins, located on the cell membrane, include carcinoembryonic antigen (CEA) and α-fetoprotein (FP). Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Tumor suppressor genes Function to regulate cell growth Suppress growth of tumors Mutations render them inactive. Result in loss of suppression of tumor growth Examples of tumor suppressor genes are BRCA-1 and BRCA-2. Another tumor suppressor gene is the APC gene. Alterations in this gene increase a person’s risk for familial adenomatous polyposis, which is a precursor for colorectal cancer. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Tumors can be classified as benign or malignant neoplasms Benign neoplasm Well differentiated Usually encapsulated Expansive mode of growth The ability of malignant tumor cells to invade and metastasize is the major difference between benign and malignant neoplasms. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Malignant neoplasm May range from well differentiated to undifferentiated Able to metastasize Infiltrative and expansive growth Frequent recurrence Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Likely to be multifactorial Origin of cancer may be Genetic Chemical Environmental Viral or immunologic May arise from causes not yet identified This is a theoretical model of the development of cancer. It is a common belief that the development of cancer is a rapid, haphazard event. However, the natural history of cancer is an orderly process comprising several stages and occurring over a period of time. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Process of Cancer Development
Fig Process of cancer development. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Initiation Mutation of cell’s genetic structure From inherited mutation From exposure to a chemical, radiation, or viral agent Mutated cell has the potential to develop into clone of neoplastic cells. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Initiation (cont’d) Once initiated, mutation is irreversible. Not all mutated cells form a tumor. Mutated cells become tumors only when they establish the ability to self-replicate and grow. Many altered cells undergo apoptosis (programmed cell death). The DNA alteration may remain undetected throughout the lifetime of an individual unless additional events stimulate the development of a tumor. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Initiation (cont’d) Carcinogens may be Chemical Radiation Viral Carcinogens can be Detoxified Harmlessly excreted In addition, some genetic anomalies increase the susceptibility of individuals to certain cancers. Common characteristics of carcinogens are that their effects in the stage of initiation are usually irreversible and additive. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Initiation (cont’d) Cells damaged by carcinogens may Self-repair Die Replicate into daughter cells with same genetic alteration Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Chemical carcinogens Long latency period makes identification of carcinogens difficult. Animal studies may not apply to humans. Certain drugs have been identified as carcinogens. Chemicals were identified as cancer-causing agents in the latter part of the eighteenth century when Percival Pott noted that chimney sweeps had a higher incidence of cancer of the scrotum associated with exposure to soot residues in chimneys. Drugs that are capable of interacting with DNA (e.g., alkylating agents) and immunosuppressive agents have the potential to cause neoplasms in humans. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Radiation Ionizing radiation can cause cancer in almost any human tissue. Dose of radiation needed to cause cancer is unknown. Ultraviolet radiation is associated with melanoma and squamous and basal cell carcinoma. Although the cause of melanoma is probably multifactorial, mounting evidence suggests that UV radiation secondary to sunlight exposure is linked to the development of melanoma. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Viral carcinogens Virus Associated Cancer Epstein-Barr virus (EBV) Burkitt’s lymphoma Human immunodeficiency virus (HIV) Kaposi sarcoma Hepatitis B virus Hepatocellular carcinoma Human papillomavirus Squamous cell carcinomas Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Promotion Characterized by reversible proliferation of altered cells Activities of promotion are reversible. Obesity Smoking, alcohol Dietary fat An important distinction between initiation and promotion is that the activity of promoters is reversible. This is a key concept in cancer prevention. Approximately half of cancer-related deaths in the United States are related to tobacco use, unhealthy diet, physical inactivity, and obesity. Some carcinogens are capable of both initiating and promoting the development of cancer. These carcinogens are termed complete carcinogens. Cigarette smoke is an example of a complete carcinogen capable of initiating and promoting cancer. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Latent period May range from 1 to 40 years Length of latent period associated with mitotic rate of tissue of origin and environmental factors For disease to be clinically evident, tumor must reach a critical mass that can be detected. A tumor that is 1.0 cm (0.4 inch) (the size usually detectable by palpation) contains 1 billion cancer cells. A 0.5-cm tumor is the smallest that can be detected by current diagnostic measures, such as magnetic resonance imaging (MRI). Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Progression Characterized by Increased growth rate of tumor Invasiveness Metastasis Most frequent sites of metastasis are lungs, brain, bone, liver, and adrenal glands. {See next 2 slides for metastasis figures} Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Main Sites of Metastasis
Fig Main sites of metastasis. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Pathogenesis of Cancer Metastasis
To produce metastases, tumor cells must detach from the primary tumor and enter the circulation, survive in the circulation to arrest in the capillary bed, adhere to capillary basement membrane, gain entrance into the organ parenchyma, respond to growth factors, proliferate and induce angiogenesis, and evade host defenses. Fig The pathogenesis of cancer metastasis. To produce metastases, tumor cells must detach from the primary tumor and enter the circulation, survive in the circulation to arrest in the capillary bed, adhere to capillary basement membrane, gain entrance into the organ parenchyma, respond to growth factors, proliferate and induce angiogenesis, and evade host defenses. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Progression (cont’d) Metastasis process begins with rapid growth of primary tumor. Develops its own blood supply Critical for survival and growth of tumor Tumor angiogenesis is formation of blood vessels within tumor. Certain segments of primary tumor can detach and invade surrounding tissues. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Development of Cancer Progression (cont’d) Metastasis process (cont’d) Detached cells can invade lymph nodes and vascular vessels to travel to distant sites. Most mobile tumor cells do not survive. Surviving tumor cells must create an environment conducive to growth and development. Once free from the primary tumor, metastatic tumor cells frequently travel to distant organ sites via lymphatic and hematogenous routes. These two routes of metastasis are interconnected. Thus it is theorized that tumor cells metastasize via both routes. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Role of Immune System Immune response is to reject or destroy cancer cells. May be inadequate as cancer cells arise from normal human cells Some cancer cells have changes on their surface antigens. Tumor-associated antigens (TAAs) {See next slide for figure} Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Tumor-Associated Antigens on Cell Surface
Fig Tumor-associated antigens appear on the cell surface of malignant cells. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Role of Immune System Immunologic surveillance Response to TAAs Lymphocytes continually check cell surface antigens and detect and destroy abnormal cells. Involves cytotoxic T cells, natural killer cells, macrophages, and B lymphocytes It has been proposed that malignant transformation occurs continuously, and that malignant cells are destroyed by the immune response. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Role of Immune System Cytotoxic T cells Kill tumor cells directly Produce cytokines Natural killer cells and activated macrophages can lyse tumor cells. B cells produce antibodies directed to tumor surface antigens. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Role of Immune System Immunologic escape Mechanism by which cancer cells evade immune system Suppression of factors that stimulate T cells Weak surface antigens allow cancer cells to “sneak through” surveillance. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Role of Immune System Immunologic escape (cont’d) Develops tolerance to immune system by some tumor antigens Suppresses immune response from products secreted by cancer cells Induction of suppressor T cells Blocking antibodies bind TAAs, preventing recognition Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Tumor Escape Mechanism
Blocking antibodies prevent T cells from interacting with tumor-associated antigens and from destroying the malignant cell. Fig Blocking antibodies prevent T cells from interacting with tumor-associated antigens and from destroying the malignant cell. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Role of Immune System Oncofetal antigens Found on tumor cell surfaces, inside tumor cells, and fetal cells Appearance of fetal antigens is not well understood. May result as cell regains its embryonic capability to differentiate into many cell types These oncofetal antigens can be used as tumor markers that may be clinically useful to monitor the effects of therapy and indicate tumor recurrence. For example, the persistence of elevated preoperative CEA titers after surgery indicates that the tumor was not completely removed. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Role of Immune System Examples of oncofetal antigens Carcinoembryonic antigen (CEA) On cancer cells of GI tract Normal cells (fetal gut, liver, and pancreas) α-Fetoprotein (AFP) Malignant liver cells and fetal liver cells Normally, CEA disappears during the last 3 months of fetal life. CEA was originally isolated from colorectal cancer cells. However, elevated CEA levels have also been found in nonmalignant conditions (e.g., cirrhosis of the liver, ulcerative colitis, heavy smoking). AFP has diagnostic value in primary cancer of the liver (hepatocellular cancer), but it is also produced when metastatic liver growth occurs. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Role of Immune System Examples of oncofetal antigens (cont’d) CA-125 CA-19-9 Prostate-specific antigen (PSA) CA 15-3, CA 27-29 kRAS HER-2 CA-125 (found in ovarian carcinoma) CA-19-9 (found in pancreatic and gallbladder cancer) CA 15-3 and CA (found in breast cancer) kRAS (expression of oncogene in colon cancer) HER-2 (expression in breast cancer) Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Classification systems provide a standardized way to Communicate with health care team Prepare and evaluate treatment plan Determine prognosis Compare groups statistically Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Anatomic site classification Identified by tissue of origin Carcinomas originate from Embryonal ectoderm (skin, glands) Endoderm (mucous membrane of respiratory tract, GI and GU tracts) Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Anatomic site classification (cont’d) Sarcomas originate from Embryonal mesoderm (connective tissue, muscle, bone, and fat) Lymphomas and leukemias originate from Hematopoietic system Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Histologic classification Appearance of cells and degree of differentiation are evaluated to determine how closely cells resemble tissue of origin. Poorly differentiated tumors have a worse prognosis than those closer in appearance to normal cells. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Four grades of abnormal cells Grade I Cells differ slightly from normal cells and are well differentiated. Grade II Cells are more abnormal and moderately differentiated. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Four grades (cont’d) Grade III Cells are very abnormal and poorly differentiated. Grade IV Cells are immature and primitive and undifferentiated. Cell of origin is difficult to determine. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Clinical staging classifications 0: Cancer in situ 1: Tumor limited to tissue of origin; localized tumor growth 2: Limited local spread 3: Extensive local and regional spread 4: Metastasis Clinical staging has been used as a basis for staging a variety of tumor types, including cancer of the cervix and Hodgkin’s lymphoma. Other malignant diseases (e.g., leukemia) do not use this staging approach. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

TNM classification system Anatomic extent of disease is based on three parameters: Tumor size and invasiveness (T) Spread to lymph nodes (N) Metastasis (M) See Table 16-5 for more information. Examples of the TNM classification system can be found in Tables and 52-6. TNM staging cannot be applied to all malignancies. For example, the leukemias are not solid tumors and therefore cannot be staged by using these guidelines. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Prevention and Detection of Cancer
Lifestyle habits to reduce risks: Avoid or reduce exposure to known or suspected carcinogens. Cigarette smoke, excessive sun exposure Eat a balanced diet. Exercise regularly. Obtain adequate rest. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Prevention and Detection of Cancer
Habits to reduce risks (cont’d) Have a regular health examination. Change perceptions of stressors. Know seven warning signs of cancer. Practice recommended cancer screenings. Practice self-examination. Seek medical care if cancer is suspected. See Table 16-6 for the seven warning signs of cancer. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Diagnoses of Cancer Patient may experience fear and anxiety. Nurse should Give clear explanations, repeat if necessary Give written information for reinforcement Actively listen to patient’s concerns When a patient has a possible diagnosis of cancer, it is a stressful time for the patient and the family. Patients may undergo several days to weeks of diagnostic studies. During this time, fear of the unknown may be more stressful than the actual diagnosis of cancer. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Diagnoses of Cancer Diagnostic plan includes Health history Identification of risk factors Physical examination Specific diagnostic studies The specifics of the health history and the screening physical examination are presented in Chapter 3. Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Diagnoses of Cancer Indicated diagnostic studies depend on site of cancer. Biopsy involves histologic examination by a pathologist of a piece of tissue. Tissue may be obtained by Needle or aspiration Incisional procedure Excisional procedure Copyright © 2011, 2007 by Mosby, Inc., an affiliate of Elsevier Inc.

Focus on Cancer: Part 1 Biology, Classification, Diagnosis

Similar presentations

Presentation on theme: "Focus on Cancer: Part 1 Biology, Classification, Diagnosis"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Focus on Cancer: Part 1 Biology, Classification, Diagnosis

Similar presentations

Presentation on theme: "Focus on Cancer: Part 1 Biology, Classification, Diagnosis"— Presentation transcript:

Similar presentations

About project

Feedback