Chapter 2 The Nature of Cancer Mar 6, 2007

Figure 2.1a The Biology of Cancer (© Garland Science 2007) 2.1 Tumors arise from normal tissues - tumor is not a foreign mass invading the body from outside world 發育不 正常的 腺癌 continuity between normal and cancerous tissue in the small intestine

2.2 Tumor arise from many cell types throughout the body The most common types of human neoplasms derive from epithelium – that is, the cells covering internal or external surfaces of the body. The neoplasms which are derived from epithelium are called “carcinomas”. These tumors are responsible for more than 80% of the cancer-related deaths.

Most of the carcinomas fall into two major categories Carcinomas arising from stratified squamous epithelium are designated squamous cell carcinomas, whereas those arising from glandular epithelium are termed adenocarcinomas.

Figure 2.6a The Biology of Cancer (© Garland Science 2007) normal squamous cells squamous cell carcinoma of the skin of the esophagus keratinocytes

mucus-secreting cells adenocarcinoma of the stomach of the stomach

The 1 st group of nonepithelial cancers derived from various connective tissues are called “ sarcomas ”, constituting ~1% of the tumors in the oncology clinic. Sarcomas derive from a variety of mesenchymal cell types: fibroblasts (connective tissues) adipocytes (fat) osteoblasts (bone) myocytes (muscle) mesenchyme: undifferentiated mesoderm-derived cells set in a gelatinous ground substance, from which connective tissue, bone, cartilage, and the circulatory and lymphatic systems develop.

Figure 2.7a The Biology of Cancer (© Garland Science 2007) osteosarcoma liposarcoma

The 2 nd group of nonepithelial cancers arise from various cell types of blood-forming tissues. lymphoma – solid tumors of lymphocytes, most frequently found in lymph nodes leukemia – tumors of “white cells” of the blood, usually moving freely through the circulation

chronic myelogenous leukemia multiple myeloma

The 3 rd group of nonepithelial tumors arises from cells of the central and peripheral nervous system Figure 2.9a The Biology of Cancer (© Garland Science 2007) astrocytes glioblastoma sympathetic ganglia cells neuroblastoma

“oma” usually indicates a tumor. For example, carcinoma, sarcoma, lymphoma, myeloma, neuroblastoma, etc. Rarely, the “oma” describes a nonneoplastic conditions such as granuloma, which is a mass of granulation tissue resulting from chronic inflammation or abscess.

Classification of Human Tumors by Tissue Type _____________________________________________________ Tissue of Origin Benign Malignant _____________________________________________________ Epithelium surface epithelium papilloma carcinoma glandular epithelium adenoma adenocarcinoma Connective tissue fibrous tissue fibroma fibrosarcoma bone osteoma osteosarcoma Endothelial tissue blood vessels hemangioma hemangiosarcoma lymph vessels lymphangioma lymphangiosarcoma

Classification of Human Tumors by Tissue Type ______________________________________________________ Tissue of Origin Benign Malignant ______________________________________________________ Neural tissue & its derivatives glial tissue glioma glioblastoma multiforme meninges meningioma meningeal sarcoma nerve sheath neurofibroma neurofibrosarcoma melanocytes pigmented nevus malignant melanoma (mole) retina 視網膜 - retinoblastoma etc. _______________________________________________________

2.4 Cancers seem to develop progressively The development of tumor is a complex, multi-step process. (Chapter 11 - Multistep tumorigenesis)

Kleinsmith, L. J. Principles of Cancer Biology. Pearson Education, Inc Fig. 1-3 Four major types of new tissue growth 肥大 增生 不正常發育 惡性增生 ( 腫瘤形成 )

Kleinsmith, L. J. Principles of Cancer Biology. Pearson Education, Inc Fig. 1-4 Comparison of normal and neoplastic growth in the epithelium of the skin In normal skin, each cell division gives rise to one cell that retains the capacity to divide and one that differentiates.

mildly hyperplasia more advanced hyperplasia normal mammary gland Hyperplasia

Dysplasia (of the cervix) no obvious invasion to the underlying stroma

Neoplasia Intraductal carcinoma of the breast

- The term neoplasm, meaning “ new growth ”, is often used interchangeably with the term tumor to signify an abnormal growth. - Tumors are of two basic types: benign & malignant. - Malignant neoplasms or cancers have distinguishing features that enable the pathologists or experimental biologists to characterize them.

A Malignant Tumor vs a Benign Tumor - depending on the degree of aggressive growth 1. Malignant tumors invade and destroy adjacent normal tissues; benign tumors grow by expansion, are usually encapsulated, and do not invade surrounding tissue. Benign tumors may, however, push aside normal tissue and become life-threatening if they press on nerves or blood vessels.

A Malignant Tumor vs a Benign Tumor 2. Malignant tumors metastasize ( 轉移 ) through lymphatic channels or blood vessels to lymph nodes and other tissues in the body. Benign tumors remain localized and do not metastasize. primary tumor – tumor growing at the anatomical site where tumor progression began and proceeded to yield this mass metastatic tumor – tumor forming at one site in the body, the cells (metastases) of which derive from a tumor located elsewhere in the body

Figure 2.2b The Biology of Cancer (© Garland Science 2007) Metastases in the liver often arise in patients with advanced colon carcinomas. Breast cancer often metastasizes to the brain.

A Malignant Tumor vs a Benign Tumor 3. Malignant tumor cells tend to be “ anaplastic ” or less differentiated than normal cells of the tissue in which they arise. Benign tumors usually resemble normal tissue more closely than malignant tumors do. anaplasia: reversion to a less differentiated structure

A Malignant Tumor vs a Benign Tumor 4. Malignant tumors usually, but not always, grow more rapidly than benign tumors. Once they reach a clinically detectable stage, malignant tumors generally show evidence of significant growth, with involvement of surrounding tissue, over weeks or months, whereas benign tumors often grow slowly over several years.

A Malignant Tumor vs a Benign Tumor 5. Malignant neoplasms continue to grow even in the face of starvation of the host; they press on and invade surrounding tissues, often interrupting vital functions. The most common effects on the patient are cachexia (extreme body wasting, 虛弱 ), hemorrhage ( 出血 ), and infection ( 感染 ).

Comparison of benign and malignant growths _____________________________________________ Feature Benign Malignant _____________________________________________ Metastasis no yes Invasion no yes Edges encapsulated irregular Growth rate low high Nuclei & nucleoli normal variable, irregular Life-threatening uncommon usual _____________________________________________ usually

Figure 2.17 The Biology of Cancer (© Garland Science 2007) 2.5 Tumors are monoclonal growths ? or?

X Chromosome Inactivation - In the somatic cells, one of the two X chromosomes is randomly (in higher mammals) inactivated in the cells of early female embryo and remains inactivated in all descendants.

Figure 2.18a The Biology of Cancer (© Garland Science 2007) M (active) or m (inactive): the X chromosome inherited from the mother (maternal) P (active) or p (inactive): the X chromosome inherited from the father (paternal)

Figure 2.18c The Biology of Cancer (© Garland Science 2007) G6PD: glucose-6- phosphate dehydrogenase

Figure 2.19a The Biology of Cancer (© Garland Science 2007) ← tumor of plasma cells Each plasma (antibody-producing) cell secrets only one kind of antibody molecule plasma

Figure 2.19b The Biology of Cancer (© Garland Science 2007) A unique translocation can be the “signature” of a particular tumor