Cancer Fundamentals. Julie Randolph-Habecker, Ph.D. Director, Experimental Histopathology Shared Resource

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1 Cancer Fundamentals Julie Randolph-Habecker, Ph.D. Director, Experimental Histopathology Shared Resource

2 Cancer Overview Leading cause of death in US 1.2 million diagnosed each year More common after age 50 Lifestyle changes can cut the cancer rate by 60% Not smoking, eating healthy diet, exercising moderately 60% of people with cancer now live longer than 5 years

3 Cancer incidence and mortality in the USA for the year 2000.

4 Cancer Incidence as a function of age. The number of newly diagnosed cases of colon cancer in woman in England and Wales in one year is plotted as a function of age at diagnosis.

5 Cancer Group of related diseases Abnormal growth of cells Rare event 30 trillion cells One renegade cell forms tumor When they spread Metastasis Cures one shoe does not fit all

6 Causes of Cancer Smoking contribute to up to 30% of cancer deaths Tobacco smoke is the most lethal carcinogen in North America Diet accounts for about 30% of cancer deaths Saturated fats High salt intake Alcohol consumption

7 Causes of Cancer Pathogens account for about 15% of cancer deaths HPV and cervical cancer HHV8 and Kaposi's Sarcoma Hepatitis B and C and liver cancer Epstein-Barr Virus and Burkitt s Lymphoma Helicobacter pylori is likely associated with stomach cancer

8 Papillomavirus DNA-based viruses Infect skin and mucous membranes Infect humans and other animals Over 100 human types

9 Causes of Cancer Radiation Environmental and Occupational Chemicals

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11 Years after exposure to 2-naphthylamine

12 Causes of Cancer Hereditary Factors Steroid Hormones Population Demographics

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14 Benign versus malignant tumors ( Good versus Evil ); the diagram illustrates types that might be found in the breast

15 Benign Tumors Leiomyoma or uterine fibroid Meningioma

16 Types of Cancer Cancers are named according to types of tissue it originated in, and what type of cell it started in e.g., ductal breast carcinoma Carcinoma: cancer of the skin and inner membranes in the body (lungs, stomach, intestines) Accounts for 90% of human cancers Sarcoma: cancer of tissue that support and connect parts of the body (muscle, bone, cartilage, and fat) Accounts for less than 2% of human cancer Leukemia and lymphomas: cancer of the bloodforming tissues Accounts for about 8% of human cancer

17 Names of Tumors Tissue Cell Type Benign tumor Malignant tumor Solid epitheila organs: liver, kidney, prostrate, thyriod, pancreas, pituitary, etc. Skin Mesenchyme: Fibrous tissue Fat Bone Cartilage Smooth muscle Striated Muscle Blood vessels Lymph nodes Reticuloendothelial: White blood cells Red blood cells Lymph nodes Specific epithelium Adenoma Carcinoma Squamous epithelium Basal cell Pigment cell Fibrocytes Adipocytes Osteocytes Chondrocytes Smooth muscle cells Muscle cells Endothelium Endothelium Myeloid cells Lymphocytes Erythrocytes Papilloma Melanoma Fibroma Lipoma Osteoma Chondroma Leiomyoma Rhabdomyoma Heamangioma Lymphangioma Squamous carcinoma Basal cell carcinoma Malignant melanoma Fibrosarcoma Liposarcoma Osteosarcoma Chondrosarcoma Leiomyosarcoma Rhabdosarcoma Heamangiosarcoma Lymphoangiosarcoma Myeloid leukemia Lympho leukemia Erythroleukaemia Non-Hodgkin s lymphoma Hodgkin s disease

18 Osteosarcoma of bone Squamous Cell Carcinoma of lung Hepatic Adenoma

19 Biology of Cancer Basement membrane METASTASIS Vessel INITIATION Chemicals, radiation, viruses Primary malignant tumor (carcinoma) DEVELOPMENT OF THE MALIGNANT PHENOTYPE Preinvasive lesion Increasing dysplasia Small benign tumor or mild dysplasia PROMOTION Exposure to carcinogens

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26 Mutation of APC on Chromosome 5 DNA loses methyl group K-RAS gene mutation Loss of DCC on Chromosome 18 p53 mutations Chromosome 17 loss Other genetic changes Normal colon cell Increase cell growth Adenoma I Adenoma II Adenoma III Carcinoma Metastasis Genetic changes and progression in colon cancer

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31 Early warning signs of cancer Changes in bowel or bladder habits A sore that does not heal Unusual bleeding or discharge Thickening or a lump in the breast or any other part of the body Indigestion or difficulty swallowing Change in appearance of a wart or mole A nagging cough or hoarseness

32 A B C D E F

33 Screening Tools Endoscopy A thin lighted tube used to look inside body cavities (esophagus, stomach, colon, intestine) Pap smear for cervical cancer Fecal occult blood test for colon cancer Blood test to look at red and white blood cell counts Prostate specific antigen (PSA) for prostate cancer X-ray (mammogram), Ultrasound, CT scan, and MRI scan Cytogenetics

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36 Karyotyping

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38 Chronic Myelogenous Leukemia (CML)

39 46,Y,der(Xq?)?inv(X)add(X),t(1;7)(p36.1;p11.2),del(3)(q23q25),del(5)(q13q33),?inv(8), der(9)add(9)(p11)add(9)q22), del(11)(q13),del(12p11.2p13),-19

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41 Tumor Staging Staging is key factor in determining treatment and prognosis Most common system: TNM = Tumor, Lymph Node, Metastasis T = size of tumor (0 to 3) N = extent of spread to lymph nodes (0 to 3) M = extent of spread throughout body (0 to 3) Example: T-1, N-0, M-0 Stage 1 tumor: tumor is 2 cm or less and has not spread to nearby lymph nodes or metastasized Prognosis is excellent Example: T-3, N-1, M-0 Stage 3 tumor: tumor is greater than 5 cm and has spread to nearby lymph nodes, but no evidence of spread to distant tissue Prognosis is mixed Stage 4 tumor = M-1 Metastasis is widespread and prognosis is poor

42 Tumor Staging Staging is key factor in determining treatment and prognosis Most common system: TNM = Tumor, Lymph Node, Metastasis T = size of tumor (0 to 3) N = extent of spread to lymph nodes (0 to 3) M = extent of spread throughout body (0 to 3)

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44 Tumor Grade Based upon microscopic appearance of a tumor A well-differentiated tumor is composed of cells that closely resemble the cell of origin Poorly differentiated tumors have cells that are difficult to recognize as to their cell of origin Associated with poor outcome Most grading systems have three or four grades (designated with numbers or roman numerals).

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46 Gleason s Pattern Well Differentiated Moderately Differentiated Poorly Differentiated

47 Other Factors

48 Treatment Surgery Effective and fast Radiation therapy Focused radiation on tumor to cause genetic damage with the goal to kill cells Targets rapidly dividing cells Chemotherapy Uses anticancer drugs to treat the whole body Sometimes used in combination with radiation therapy (e.g., breast, lung, colon, prostate)

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50 Treatment Hormone therapy Prevent cancer cells from using or receiving the hormones they need to grow/survive e.g., tamoxifen and raloxifene are antiestrogen drugs

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52 Treatment Biological therapy Immunotherapy Uses body s immune system to eliminate cancer cells Uses antibodies to direct attack the tumor or to deliver toxic agents Herceptin is an antibody that targets cells that overproduce HER-2 Bone marrow transplantation

53 How does cancer kill Multisystem organ failure Infection 32-47% Hemorrhage & Thromboembolism 10-20% Cachexia >1%

54 Areas of Cancer Research Prevention Nutrition Tobacco Detection Early Detection and Intervention Treatment Environmental Carcinogenesis/ toxicology Causes/etiology

55 Early Detection and Intervention Using models of cancer Analyzing samples with Proteomics Identify small molecules associated with cancer Test on archived patient samples Develop screening tools for early detection Sensitive and specific Non-invasive

56 Research for Understanding Yeast Led to an understanding of how the control of cell division Chemistry Lipid chemistry to develop drugs Viruses Research on chicken virus helped identify oncogenes

57 Clinical trials Research studies in which new treatments (e.g., drugs, diagnostic procedure, vaccines) are tested in people to see if they are safe and effective All new treatments must go through clinical trials

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59 Future Research Directions Better detection/diagnosis Target vasculature Prevent metastases Gene therapy

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65 Veiseh, M. et al. Cancer Res 2007;67: Copyright 2007 American Association for Cancer Research

66 Questions? Thanks: Karen Peterson Michele Talquist Eileen Bryant Jim Olson

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