Oncology

Mark Bower, Jonathan Waxman

• Publisher: Wiley-Blackwell
• Year: 2011
• Print ISBN: 9781405195133
• eBook ISBN: 9781118293003
• Edition: 2
• Topic: Medicine
• Subtopic: Oncology

Cancer is one of the most rapidly changing areas of medicine, affecting ever-increasing numbers of people, and this new edition of Lecture Notes: Oncology brings together all the information a medical student or graduate clinician needs in one accessible volume. It covers the scientific basis and social impact of cancer, describes the origins and presentations of cancer on a regional and system basis, and discusses the fundamentals of oncology treatment and patient management.

Including a new section on epigenetics, clinical vignettes, clear illustrations, tables and diagrams, as well as a self-test section of MCQs, Lecture Notes: Oncology provides core knowledge for professionals involved in cancer care.

Part 1

Introduction to Oncology

Chapter 1

What is cancer?

Cancer is not a single illness but a collection of many diseases that share common features. Cancer is widely viewed as a disease of genetic origin. It is caused by mutations of DNA and epigenetic changes that alter gene expression, which make a cell multiply uncontrollably. However, the description and definitions of cancer vary depending on the perspective as described below.

Epidemiological perspective

Cancer is a major cause of morbidity in the United Kingdom with around 289 000 new cases diagnosed in 2005. There are more than 200 different types of cancer, but four of them (breast, lung, colorectal and prostate) account for over half of all new cases. Overall it is estimated that one in three people will develop some form of cancer during their lifetime. In the 30-year period 1976–2005 the overall age-standardized incidence rates for cancer increased by 35% in men and 16% in women but have remained fairly constant over the last decade (1996-2005). The cancers whose incidence is rising fastest in men are malignant melanoma, mesothelioma, prostate cancer and hepatocellular cancer, while in women they are mesothelioma, melanoma, endometrial cancer and oral cancer.

Cancer incidence refers to the number of new cancer cases arising in a specified period of time. Prevalence refers to the number of people who have received a diagnosis of cancer who are alive at any given time, some of whom will be cured and others will not. Therefore prevalence reflects both the incidence of cancer and its associated survival pattern. In 2008 approximately 3% of the population of the UK (around two million people) are alive having received a diagnosis of cancer. The single cancer that contributes most to the prevalence is breast cancer, with an estimated 550 000 women alive who have had a diagnosis of breast cancer.

Sociological perspective

Patients with cancer adopt a medically sanctioned form of deviant behaviour described in the 1950s by Talcott Parsons as ‘the sick role’. In order to be excused their usual duties and to not be considered responsible for their illness, patients are expected to seek professional advice and to adhere to treatments in order to get well. Medical practitioners are empowered to sanction their temporary absence from the workforce and family duties as well as to absolve them of blame. This behavioural model minimizes the impact of illness on society and reduces the secondary gain that the patient benefits from as a consequence of their illness. However, as Ivan Illich pointed out it also sets up physicians as agents of social control by medicalizing health and contributing to iatrogenic illness – ‘a medical nemesis’. Of all the common medical diagnoses, cancer probably carries the greatest stigma and is associated with the most fear. The many different ways in which cancer affects people has been explored in literature (Table 1.1).

Table 1.1 The top cancer books (in the authors’ opinion).

	Title	Author
1	Cancer Ward	Alexander Solzhenitsyn
2	A Very Easy Death	Simone de Beauvoir
3	Age of Iron	J. M. Coetzee
4	Cancer Vixen	Marisa Acocella Marchetto
5	One in Three	Adam Wishart
6	C: Because Cowards get Cancer, Too	John Diamond
7	Before I Say Goodbye	Ruth Picardie
8	Illness as Metaphor	Susan Sontag
9	The Black swan	Thomas Mann
10	Mom’s Cancer	Brian Fies
11	Coda	Simon Gray
12	Cancer Tales	Nell Dunn

Experimental perspective

In the laboratory, a number of characteristics define a cancer cell growing in culture. The four features listed below are used by scientists experimentally to confirm the malignant phenotype of cancer cells:

1. Cancer cells are clonal, having all derived from a single parent cell.

2. Cancer cells grow on soft agar, in the absence of growth factors.

3. Cancer cells cross artificial membranes in culture systems.

4. Cancer cells form tumours if injected into immunodeficient strains of mice (Box 1.1).

Histopathological perspective

Cancer is usually defined by various histopathological features, most notably invasion and metastasis, that are observed by gross pathological and microscopic examinations. Laminin staining of the basement membrane may assist the histopathologist in identifying local invasion by tumours that breach the basement membrane. In addition a number of microscopic features point to the diagnosis of cancer:

Box 1.1: Onco-mice

Mice have been used as a laboratory model in cancer research for a century. In the 1930s, Sir Ernest Kennaway showed that polycyclic aromatic hydrocarbons were carcinogenic by inducing skin cancers in mice. In 1969 the first inbred mice were developed that were essentially genetically identical except for gender. These strains allowed the transfer of cells and tissues between mice without rejection as they are syngeneic (genetically identical). This has allowed the effects of experimental treatments on murine cancers to be evaluated in laboratory mice. Some inbred strains also spontaneously develop cancers (e.g. BALB/c mice frequently develop lung tumours) so that the effects of cancer prevention strategies can be studied. The development of immunodeficient mice allowed the transfer and study of human cancer cells in mice without the mice rejecting the xenograft (graft between different species). The first immunodeficient mice were ‘nude mice’, an inbred strain that lacks a thymus gland and T lymphocytes; they are hairless because of a mutation in a linked genetic locus. Subsequently, in 1983, even more immunodeficient SCID (severe combined immunodeficiency) mice were developed that lack both T and B cells. Genetically modified transgenic mice have been manufactured by knocking out specific genes (‘knockout mice’) or adding extra trans-genes, usually from different species (‘transgenic mice’), to embryonic stem cells. These mice are used to elucidate the influence of individual genes on the phenotype. Finally, mice were the original source of monoclonal antibodies produced by immunizing inbred mice with the desired antigen and fusing spleen cells from the mouse with myeloma cells to yield hybridoma cells that produce monoclonal antibodies.

• Cancer cells differ morphologically from normal cells
• Tumour architecture is less organized than that of the parent tissue
• Cancer cells have increased nuclear DNA and nuclear:cytoplasmic ratio
• Cancer cells have hyperchromatic nuclei with coarsening of chromatin and wrinkled nuclear edges
• Cancer cells may be multinucleated or have macronucleoli
• Cancer cells may have numerous and bizarre mitotic figures

Cancers may be heterogenous with cells of varying sizes and orientation with respect to one another despite their clonal origin.

Molecular perspective

The molecular features that identify a cancer are described in ‘Six steps to becoming a cancer’ in Chapter 2. These six properties are:

1. Grow without a trigger (self-sufficiency in growth stimuli).

2. Don’t stop growing (insensitivity to inhibitory stimuli).

3. Don’t die (evasion of apoptosis).

4. Don’t age (immortalization).

5. Feed themselves (neoangiogenesis).

6. Spread (invasion and metastasis).

How to read a histology report

The diagnosis of cancer is most commonly established following a histopathological report of a biopsy or tumour resection. A histopathological report should include both gross pathological features (tumour size and number and size of lymph nodes examined) and microscopic findings (tumour grade, architecture, mitotic rate, margin involvement and lymphovascular invasion). The grade and stage of a cancer are important prognostic factors that may influence therapy options (Box 1.2).

Box 1.2: Histopathology definitions

Quantitative changes: too small

Atrophy

Acquired shrinkage due to a decrease in the size or number of cells of a tissue, e.g. decrease in size of the ovaries after the menopause.

Quantitative changes: too big

Hypertrophy

Increase in the size of an organ or tissue due to an increase in the size of individual cells, e.g. pregnant uterus.

Hyperplasia

Increase in the size of an organ due to an increase in the number of cells, e.g. lactating breast.

Qualitative changes

Metaplasia

Re...

Table of contents

• Cover
• Title Page
• Copyright
• Preface to the second edition
• Part 1: Introduction to Oncology
• Part 2: Types of Cancer
• Part 3: The Practice of Oncology
• Self-assessment MCQs
• Answers to MCQs
• Colour plate section faces
• Index