Tumor Pathology 3+4 Flashcards
List the local effects of cancer.
- Mass Effect
Compression of Nearby Structures: Tumors can press against surrounding tissues, leading to dysfunction or pain in affected organs. For example, a lung tumor may compress the airways. - Obstruction
Blockage of Passageways: Tumors can obstruct ducts or passages, such as bile ducts in the liver or intestines, leading to symptoms like jaundice or bowel obstruction. - Pain
Localized Pain: Tumors can cause pain directly through pressure on nerves or tissues, or indirectly by causing inflammation or irritation in surrounding areas. - Ulceration
Breakdown of Tissue: Cancer can lead to the breakdown of surrounding tissues, resulting in ulcers, particularly in cancers affecting the skin or gastrointestinal tract. - Inflammation
Localized Inflammatory Response: The presence of a tumor can trigger an inflammatory response, leading to redness, swelling, and discomfort in the affected area. - Distortion of Normal Anatomy
Alteration of Organ Structure: Tumors can distort the normal shape and structure of organs, which may affect their function. For instance, a tumor in the brain can change brain structure and pressure dynamics. - Functional Impairment
Loss of Function: Depending on the location, tumors can impair the function of affected organs, such as the heart, lungs, or kidneys, leading to significant clinical symptoms. - Cachexia
Weight Loss and Muscle Wasting: Some cancers can lead to cachexia, a syndrome characterized by significant weight loss and muscle wasting, often due to metabolic changes and local tumor effects. - Fistula Formation
Abnormal Connections Between Organs: In some cases, tumors can erode through tissues and create abnormal connections between organs (fistulas), which can lead to complications. - Neurological Effects
Nerve Involvement: Tumors in proximity to nerves can lead to neurological symptoms such as weakness, numbness, or altered sensation.
List the systemic effects of cancer.
- Weight Loss and Cachexia
Unintentional Weight Loss: Many cancer patients experience significant weight loss, often accompanied by muscle wasting (cachexia), due to increased metabolic demands and reduced appetite. - Fatigue
Persistent Tiredness: Cancer and its treatments can lead to profound fatigue that doesn’t improve with rest, affecting daily activities and quality of life. - Anemia
Low Red Blood Cell Count: Cancer can cause anemia, either directly (due to the disease) or as a side effect of treatments, leading to weakness, fatigue, and pallor. - Fever
Persistent Low-Grade Fever: Some cancers can induce a systemic inflammatory response, resulting in persistent fevers. - Night Sweats
Excessive Sweating: Many patients experience night sweats, often associated with certain types of cancer, such as lymphomas. - Hypercalcemia
Elevated Calcium Levels: Certain cancers can cause the release of calcium from bones into the bloodstream, leading to symptoms like nausea, confusion, and weakness. - Hormonal Changes
Endocrine Effects: Some tumors can produce hormones or hormone-like substances, causing systemic effects (e.g., Cushing’s syndrome from adrenal tumors). - Immunosuppression
Increased Infection Risk: Cancer can weaken the immune system, either through the disease itself or as a side effect of treatments, leading to a higher risk of infections. - Blood Clots
Thrombosis: Cancer increases the risk of thrombosis (blood clots), which can lead to complications such as deep vein thrombosis (DVT) or pulmonary embolism (PE). - Paraneoplastic Syndromes
Remote Effects: Certain cancers can cause paraneoplastic syndromes, where the tumor produces substances that affect other body systems, leading to neurological, endocrine, or hematological symptoms. - Psychological Effects
Mental Health Impact: The diagnosis and experience of cancer can lead to anxiety, depression, and other psychological challenges, affecting overall well-being.
Identify the concepts of dysplasia and intra-epithelial neoplasia.
> Dysplasia
- Definition: Dysplasia refers to an abnormal growth or development of cells within a tissue, characterized by changes in cell size, shape, and organization. It often indicates a pre-cancerous condition.
- Features:
+ Cellular Abnormalities: Dysplastic cells may show increased nuclear-to-cytoplasmic ratio, irregular nuclear shapes, and variations in cell size (pleomorphism).
+ Loss of Normal Architecture: The tissue structure becomes disorganized, which can be observed histologically.
+ Reversible Changes: In some cases, dysplasia can be reversed if the underlying cause (such as irritation or inflammation) is removed. - Types: Dysplasia can be classified as mild, moderate, or severe, depending on the degree of cellular abnormality. Severe dysplasia is often considered a precursor to cancer.
> Intra-Epithelial Neoplasia (IEN)
- Definition: Intra-epithelial neoplasia refers to a spectrum of changes within epithelial tissue that ranges from mild dysplasia to more severe forms, indicating an increased risk of progression to invasive cancer. It is often used to describe pre-cancerous lesions.
- Types:
+ Low-Grade Intra-Epithelial Neoplasia (LGIEN): Represents early changes with a lower risk of progression to cancer. Often reversible.
-+High-Grade Intra-Epithelial Neoplasia (HGIEN): Indicates more significant cellular abnormalities and a higher likelihood of progressing to invasive cancer if left untreated. - Examples:
+ Cervical Intra-Epithelial Neoplasia (CIN): Refers to precancerous changes in cervical cells, categorized as CIN I (low-grade), CIN II (moderate-grade), and CIN III (high-grade).
+ Ductal Carcinoma In Situ (DCIS): Refers to high-grade changes in breast ductal epithelium without invasion into surrounding tissues.
Describe some key processes and genes in the cell cycle.
> Key Phases of the Cell Cycle
1. G1 Phase (Gap 1) - Cell grows and prepares for DNA replication. It checks for DNA damage and sufficient resources.
- S Phase (Synthesis) - DNA replication occurs, resulting in the duplication of the chromosomes.
- G2 Phase (Gap 2) - The cell continues to grow and prepares for mitosis. It checks for DNA damage and ensures all DNA is replicated.
- M Phase (Mitosis) - The cell divides its copied DNA and cytoplasm to form two daughter cells.
= Key Processes
> Cell Cycle Checkpoints:
- G1 Checkpoint: Checks for DNA damage, cell size, and nutrient availability. If conditions aren’t met, the cell may enter a resting state (G0).
- G2 Checkpoint: Ensures DNA has been replicated correctly and checks for DNA damage before mitosis.
- M Checkpoint (Spindle Checkpoint): Ensures all chromosomes are properly attached to the spindle apparatus before proceeding with mitosis.
> Cyclins and Cyclin-Dependent Kinases (CDKs);
- Cyclins: Regulatory proteins that control the progression of the cell cycle by activating CDKs.
- CDKs: Enzymes that, when activated by cyclins, phosphorylate target proteins to drive the cell cycle forward.
= Key Genes
1. Cyclin Genes
- CCND1 (Cyclin D1): Promotes progression through the G1 phase. Its expression is often upregulated in cancers.
- CCNE1 (Cyclin E): Regulates the G1/S transition, allowing the cell to enter the S phase.
- CDK Genes
- CDK2: Partners with Cyclin E to regulate the G1/S transition and with Cyclin A during the S phase.
- CDK1 (CDC2): Partners with Cyclin B to control the G2/M transition. - Tumor Suppressor Genes
- TP53 (p53): Acts as a checkpoint regulator, inducing cell cycle arrest in response to DNA damage, allowing for repair or triggering apoptosis if damage is irreparable.
- RB (Retinoblastoma protein): Regulates the G1 checkpoint by inhibiting progression to the S phase until conditions are favorable. - Oncogenes
- MYC: A transcription factor that promotes cell cycle progression and is often overexpressed in cancers.
- RAS: A signaling protein that can promote cell growth and division when mutated.
> Summary
The cell cycle is a highly regulated process involving a complex interplay of cyclins, CDKs, checkpoints, and various genes. Disruptions in these processes can lead to uncontrolled cell growth and cancer. Understanding these mechanisms is essential for developing cancer therapies and treatments targeting the cell cycle.
Describe what an oncogene and tumour suppressor gene are.
= Oncogenes
- Definition: Oncogenes are mutated or overexpressed versions of normal genes (proto-oncogenes) that promote cell growth and division. When these genes are altered, they can lead to uncontrolled cell proliferation, contributing to cancer development.
> Characteristics:
- Gain-of-Function Mutations: Oncogenes typically result from mutations that enhance their activity or lead to the production of an active protein.
- Examples of Oncogenes:
~ Ras: A signaling protein that, when mutated, can continuously promote cell division.
~ Myc: A transcription factor that stimulates cell proliferation and growth.
~ HER2 (ERBB2): A receptor tyrosine kinase that, when overexpressed, is associated with aggressive breast cancer.
Function: Oncogenes promote processes such as:
- Cell proliferation
- Inhibition of apoptosis (programmed cell death)
- Increased survival of cells
= Tumor Suppressor Genes
- Definition: Tumor suppressor genes are normal genes that regulate cell division and prevent uncontrolled cell growth. When these genes are mutated or inactivated, their protective effects are lost, leading to an increased risk of cancer.
> Characteristics:
- Loss-of-Function Mutations: Tumor suppressor gene mutations usually result in a decrease or complete loss of function.
- Examples of Tumor Suppressor Genes:
~ TP53 (p53): A critical regulator of the cell cycle that induces cell cycle arrest, DNA repair, or apoptosis in response to DNA damage.
~ RB (Retinoblastoma protein): Regulates the G1/S checkpoint, preventing cells from entering the S phase when conditions are unfavorable.
~ BRCA1 and BRCA2: Genes involved in DNA repair; mutations are linked to increased breast and ovarian cancer risk.
> Function: Tumor suppressor genes help:
- Control the cell cycle
- Induce apoptosis in damaged cells
- Maintain genomic stability
Summary
In summary, oncogenes drive the process of cancer by promoting uncontrolled cell growth and division, while tumor suppressor genes act as safeguards against cancer by regulating cell growth and initiating repair mechanisms. The balance between these two types of genes is crucial for maintaining normal cellular function and preventing tumorigenesis. When the balance is disrupted, it can lead to the development and progression of cancer.
Understand environmental versus inherited factors in carcinogenesis.
- Environmental Factors
Definition: Environmental factors are external agents or conditions that can contribute to the development of cancer. These factors can influence the genetic material in cells or affect cellular processes. - Types of Environmental Factors:
> Chemical Carcinogens:
. Tobacco Smoke: Contains numerous carcinogenic substances linked to lung and other cancers.
. Asbestos: Associated with mesothelioma and lung cancer.
. Aflatoxins: Produced by certain molds, linked to liver cancer.
> Physical Carcinogens:
. Radiation: Ionizing radiation (like X-rays) and ultraviolet (UV) radiation from the sun can cause DNA damage leading to skin cancer (e.g., melanoma).
. Radon Gas: A naturally occurring radioactive gas that can lead to lung cancer when inhaled.
> Biological Carcinogens:
. Viruses: Certain viruses are known to cause cancer, such as human papillomavirus (HPV) linked to cervical cancer and hepatitis B and C viruses linked to liver cancer.
. Bacteria: Helicobacter pylori infection is associated with stomach cancer.
> Lifestyle Factors:
. Diet: High consumption of processed foods and red meats may increase cancer risk, while a diet rich in fruits and vegetables may offer protective benefits.
. Alcohol Consumption: Excessive alcohol intake is associated with various cancers, including breast and liver cancer.
. Obesity: Excess body weight is a risk factor for several types of cancer.
> Inherited Factors
Definition: Inherited factors refer to genetic predispositions passed down from parents to offspring. These can increase an individual’s susceptibility to certain types of cancer.
> Types of Inherited Factors:
- Genetic Mutations:
. Hereditary Cancer Syndromes: Certain genetic mutations significantly increase cancer risk, such as:
~ BRCA1 and BRCA2: Mutations in these genes are linked to a higher risk of breast and ovarian cancer.
~ Lynch Syndrome: Caused by mutations in mismatch repair genes, increasing the risk of colorectal and endometrial cancers.
> Family History:
- A family history of certain cancers can indicate a genetic predisposition. For example, multiple cases of breast cancer in a family may suggest the presence of hereditary factors.
Single Nucleotide Polymorphisms (SNPs):
- Variations in DNA sequence that may affect an individual’s response to environmental carcinogens or influence cancer risk.
- Interaction Between Environmental and Inherited Factors
- Gene-Environment Interactions: The risk of developing cancer is often the result of interactions between inherited genetic predispositions and environmental exposures. For instance, individuals with certain genetic mutations may have a heightened risk when exposed to specific carcinogens.
- Modification of Risk: Lifestyle choices (such as diet and exercise) can influence the expression of inherited risk factors, potentially modifying cancer risk.
Understand the multistep nature of carcinogenesis.
Key Stages of Carcinogenesis
1.Initiation
-Genetic Alterations: The first step involves a genetic mutation that may result from exposure to carcinogens (e.g., chemicals, radiation) or spontaneous errors in DNA replication. These mutations can affect oncogenes, tumor suppressor genes, or genes involved in DNA repair.
-Irreversible Change: Initiation is often an irreversible process, as the mutation becomes fixed in the cell’s DNA.
- Promotion
- Clonal Expansion: After initiation, certain factors (promoters) can stimulate the proliferation of the initiated cells. These promoters may not be directly carcinogenic but create an environment conducive to growth (e.g., hormones, inflammation).
- Reversible Changes: Promotion is generally reversible, meaning that removing the promoting agent can stop the progression of abnormal cells. - Progression
- Further Genetic Changes: During this phase, additional mutations accumulate, leading to increasingly abnormal behavior in the cells. This may include enhanced growth rates, invasiveness, and the ability to evade apoptosis.
- Malignant Transformation: The cells may begin to exhibit characteristics of cancer, such as loss of differentiation and increased heterogeneity. The tumor can also acquire the ability to metastasize.
Key Concepts in Multistep Carcinogenesis:
> Tumor Heterogeneity: As cancer progresses, the tumor becomes increasingly heterogeneous, with variations in genetic and phenotypic characteristics among the cells. This diversity can affect the tumor’s behavior and response to treatment.
> Field Cancerization: The concept that a region of tissue can undergo widespread genetic alterations due to exposure to carcinogenic factors, increasing the likelihood of multiple tumors developing in that area over time.
> Genetic Instability: Many cancer cells exhibit genomic instability, leading to a higher mutation rate. This instability can accelerate the accumulation of mutations that drive tumor progression.
> Microenvironmental Factors: The surrounding stroma, including immune cells, blood vessels, and extracellular matrix, plays a crucial role in tumor development and progression, influencing how cancer cells behave.
- Examples of Multistep Carcinogenesis
1. Colorectal Cancer:
Often follows the adenoma-carcinoma sequence, where benign polyps (adenomas) develop into malignant tumors through sequential mutations in oncogenes (e.g., KRAS) and tumor suppressor genes (e.g., APC, p53).
- Breast Cancer:
Can involve mutations in genes such as BRCA1 and BRCA2, along with additional genetic changes leading to the progression from ductal hyperplasia to carcinoma in situ and then invasive breast cancer.
