Oncology and Tumor Biology

Epidemiology

100

What is the most common cancer in the world? (A) Breast (B) Gastric (C) Lung (D) Liver

ANS C Lung cancer is the leading cancer in the world, accounting for 1.35 million new cases and 1.15 million deaths per year. Breast cancer is now the second most common cause of cancer (1.15 million cases per year) followed by gastric cancer (934,000 cases), colorectal cancer (1.03 million cases), and liver cancer (626,000 case). (See Schwartz 9th ed., Chapter 10, Oncology.)

200

Which of the following is NOT one of the six cell alterations that permit malignant growth to occur in cells? (A) Self-sufficiency of growth signals (B) Predisposition to apoptosis (C) Angiogenesis (D) Invasion and metastasis

ANS B Explanation:Although there are >100 types of cancer, it has been proposed that there are six essential alterations in cell physiology that dictate malignant growth: self-sufficiency of growth signals, insensitivity to growth-inhibitory signals, evasion of apoptosis (programmed cell death), potential for limitless replication, angiogenesis, and invasion and metastasis (Fig. 10-1). (See Schwartz 9th ed., Chapter 10, Oncology.)

300

Which of the following is associated with an increased incidence of liver cancer? (A) Salted food (B) Infection with Hepatitis A (C) Exposure to aflatoxin (D) Helicobacter pylori

ANS: C. Explanation:In contrast to colon cancers, 82% of liver cancers occur in developing countries. The incidence of liver cancer is especially high in China (37.9 per 100,000 men), whereas it is relatively low in North and South America and Europe (2.6 to 6.2 per 100,000 men). Worldwide, the major risk factors for liver cancer are infection with hepatitis B and C viruses and consumption of foods contaminated with aflatoxin. Hepatitis B immunization in children has recently been shown to reduce the incidence of liver cancer. (See Schwartz 9th ed., Chapter 10, Oncology.)

400

Approximately how many people die of cancer annually in the United States? (A) 100,000 (B) 500,000 (C) 2,000,000 (D) 5,000,000

ANS B Explanation:In the year 2008, an estimated 1.44 million new cancer cases were diagnosed in the United States. An estimated 565,650 people were expected to die of cancer in the United States in the same year. Cancer deaths accounted for 23% of all deaths in the United States in 2005, second only to deaths from heart disease. (See Schwartz 9th ed., Chapter 10, Oncology.)

500

Which of the following chemical carcinogens has been associated with angiosarcoma of the liver? (A) Benzene (B) Diethylstilbestrol (C) Vinyl chloride (D) Coal tar

ANS: C Vinyl chloride is associated with angiosarcoma of the liver, hepatocellular carcinoma, brain tumors, lung cancer, malignancies of lymphatic and hematopoietic system

Cancer Biology

100

Which of the following is INCORRECT? (A) A feature of malignant cells is invasion (B) In situ cancer lies above the basement membrane (C) Invasion involves changes in adhesion, motility, and proteolysis of extracellular matrix (D) E-cadherin molecules increase invasion

ANS: D. A feature of malignant cells is their ability to invade the surrounding normal tissue. Tumors in which the malignant cells appear to lie exclusively above the basement membrane are referred to as in situ cancer, whereas tumors in which the malignant cells are demonstrated to breach the basement membrane, penetrating into surrounding stroma, are termed invasive cancer. The ability to invade involves changes in adhesion, initiation of motility, and proteolysis of the extracellular matrix (ECM). Cell-to-cell adhesion in normal cells involves interactions between cell-surface proteins. Calcium adhesion molecules of the cadherin family (E-cadherin, P-cadherin, and N-cadherin) are thought to enhance the cells' ability to bind to one another and suppress invasion. (See Schwartz 9th ed., Chapter 10, Oncology.)

200

Malignant cells are LEAST likely to be in which of the following stages of the cell cycle? (A) S phase (B) G0 phase (C) G1 phase (D) M phase

ANS B Explanation:Malignant cells are cells that do not enter the G0 stage (quiescent stage) after proliferation. The proliferative advantage of tumor cells is a result of their ability to bypass quiescence. Cancer cells often show alterations in signal transduction pathways that lead to proliferation in response to external signals. When cells cease proliferation, they exit the cell cycle and enter the quiescent state referred to as G0. (See Schwartz 9th ed., Chapter 10, Oncology.)

300

A "field effect" is best described as (A) The effect of oncogene amplification in a cell on the adjacent cells (B) The effect of loss of tumor-suppressor gene function in a cell on the adjacent cells (C) Increased oncogene amplification or loss of tumor-suppressor gene function in a group of cells (D) The effect of radiation on a tumor

ANS C Explanation:Tumorigenesis is proposed to have three steps: initiation, promotion and progression. Initiating events such as gain of function of genes known as oncogenes or loss of function of genes known as tumor-suppressor genes may lead a single cell to acquire a distinct growth advantage. Although tumors usually arise from a single cell or clone, it is thought that sometimes not a single cell but rather a large number of cells in a target organ may have undergone the initiating genetic event; thus many normal-appearing cells may have an elevated malignant potential. This is referred to as a field effect. The initiating events are usually genetic and occur as deletions of tumor-suppressor genes or amplification of oncogenes. Subsequent events can lead to accumulations of additional deleterious mutations in the clone. (See Schwartz 9th ed., Chapter 10, Oncology.)

400

Which of the following occurs in abnormally proliferating, transformed cells? (A) Anchorage-dependent growth (B) Immortalization (C) Increased contact inhibition (D) Increased cell-cell adherence

ANS B In normal cells, cell growth and proliferation are under strict control. In cancer cells, cells become unresponsive to normal growth controls, which leads to uncontrolled growth and proliferation. Human cells require several genetic changes for neoplastic transformation. Cell type–specific differences also exist for tumorigenic transformation. Abnormally proliferating, transformed cells outgrow normal cells in the culture dish (i.e., in vitro) and commonly display several abnormal characteristics. These include loss of contact inhibition (i.e., cells continue to proliferate after a confluent monolayer is formed); an altered appearance and poor adherence to other cells or to the substratum; loss of anchorage dependence for growth; immortalization; and gain of tumorigenicity (i.e., the ability to give rise to tumors when injected into an appropriate host). (See Schwartz 9th ed., Chapter 10, Oncology.)

500

HER2, also known as neu, is an oncogene that promotes malignant potential by (A) Forming a hetrodimer with other EGFR members (B) Increasing cell proliferation and growth (C) Suppressing apoptosis (D) All of the above

ANS D HER2 can interact with different members of the EGFR family and regulate mitogenic and survival signaling (Fig 10-3). (See Schwartz 9th ed., Chapter 10, Oncology.)

Cancer Syndromes

100

Which of the following is the most common etiology of Li-Fraumeni syndrome? (A) Exposure to aflatoxin (B) Exposure to radiation (C) Mutation in the p53 gene (D) Mutation in the BRCA1 gene

ANS C Approximately 70% of LFS families have been shown to have germline mutations in the tumor-suppressor gene p53. Breast carcinoma, soft tissue sarcoma, osteosarcoma, brain tumors, adrenocortical carcinoma, Wilms' tumor, and phyllodes tumor of the breast are strongly associated; pancreatic cancer is moderately associated; and leukemia and neuroblastoma are weakly associated with germline p53 mutations. Mutations of p53 have not been detected in approximately 30% of LFS families, and it is hypothesized that genetic alterations in other proteins interacting with p53 function may play a role in these families. (See Schwartz 9th ed., Chapter 10, Oncology.)

200

What percentage of breast cancers are hereditary? (A) <1% (B) 5-10% (C) 30% (D) 50%

ANS B It is estimated that 5 to 10% of breast cancers are hereditary. Of women with early-onset breast cancer (aged 40 years or younger), nearly 10% have a germline mutation in one of the breast cancer genes BRCA1 or BRCA2. Mutation carriers are more prevalent among women who have a first- or second-degree relative with premenopausal breast cancer or ovarian cancer at any age. The likelihood of a BRCA mutation is higher in patients who belong to a population in which founder mutations may be prevalent, such as in the Ashkenazi Jewish population. (See Schwartz 9th ed., Chapter 10, Oncology.)

300

Patients with hereditary melanoma due to a p16 mutation are also at higher risk for (A) Thyroid cancer (B) Pancreatic cancer (C) Colorectal cancer (D) Breast cancer

ANS: B. The gene P16 is a tumor suppressor gene. Studies suggest that germline mutations in p16 can be found in 20% of melanoma-prone families. Mutations in p16 that alter its ability to inhibit the catalytic activity of the CDK4-CDK6/cyclin D complex not only increase the risk of melanoma by 75-fold but also increase the risk of pancreatic cancer by 22-fold. (See Schwartz 9th ed., Chapter 10, Oncology.)

400

BRCA2 mutations are associated with all of the following EXCEPT (A) Gastric cancer (B) Lung cancer (C) Ovarian cancer (D) Prostate cancer

ANS B Besides breast and ovarian cancer, BRCA1 and BRCA2 mutations may be associated with increased risks for several other cancers. BRCA1 mutations confer a fourfold increased risk for colon cancer and threefold increased risk for prostate cancer. BRCA2 mutations confer a fivefold increased risk for prostate cancer, sevenfold in men younger than 65 years. Furthermore, BRCA2 mutations confer a fivefold increased risk for gallbladder and bile duct cancers, fourfold increased risk for pancreatic cancer, and threefold increased risk for gastric cancer and malignant melanoma. (See Schwartz 9th ed., Chapter 10, Oncology.)

500

Mutations in the Rb1 gene were first associated with (A) Breast cancer (B) Colorectal cancer (C) Rhabdomyosarcoma (D) Retinoblastoma

ANS D

Cancer Diagnosis and Screening

100

Which of the following molecularly targeted therapies is directed against the HER2 gene? (A) Cetuximab (B) Sunitinib (C) Trastuzumab (D) Temsirolimus

ANS C. Traztuzamab = Herceptin

200

A patient with breast cancer is considered to be cancer free (no further risk of primary recurrence or metastatic tumor) after (A) 3 years (B) 5 years (C) 10 years (D) Never

ANS D. Metastases can sometimes arise several years after the treatment of primary tumors. For example, although most breast cancer recurrences occur within the first 10 years after the initial treatment and recurrences are rare after 20 years, breast cancer recurrences have been reported decades after the original tumor. This phenomenon is referred to as dormancy. (See Schwartz 9th ed., Chapter 10, Oncology.)

300

Tumor staging for most epithelial cancers includes all of the following EXCEPT (A) Tumor size (B) Tumor mutations (C) Nodal involvement (D) Distant spread

ANS B Standardization of staging systems is essential to allow comparison of results from different studies from different institutions and worldwide. The staging systems proposed by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (International Union Against Cancer, or UICC) are among the most widely accepted staging systems. Both the AJCC and the UICC have adopted a shared tumor, node, and metastasis (TNM) staging system that defines the cancer in terms of the anatomic extent of disease and is based on assessment of three components: the size of the primary tumor (T), the presence (or absence) and extent of nodal metastases (N), and the presence (or absence) and extent of distant metastases (M). (See Schwartz 9th ed., Chapter 10, Oncology.)

400

The risk of developing breast cancer by age 70 for a woman with a BRCA1 mutation is approximately (A) 20% (B) 40% (C) 60% (D) 80%

ANS D For a female BRCA1 mutation carrier, the cumulative risks of developing breast cancer and ovarian cancer by age 70 have been estimated to be 87 and 44%, respectively. The cumulative risks of breast cancer and ovarian cancer by age 70 in families with BRCA2 mutation have been estimated to be 84 and 27%, respectively. Although male breast cancer can occur with either BRCA1 or BRCA2 mutation, the majority of families (76%) with both male and female breast cancer have mutations in BRCA2. (See Schwartz 9th ed., Chapter 10, Oncology.)

500

For average-risk patients, routine cancer screening is recommended for all but the following disease? (A) Breast cancer (B) Colorectal cancer (C) Cervical cancer (D) Pancreatic cancer

ANS D

"Yeah, I read the chapter..."

100

Which of these histologic findings is considered pathognomonic for Hodgkin's lymphoma? (A) Mikulicz's cells (B) Charcot-Leyden crystals (C) Birbeck granules (D) Reed-Sternberg cells (E) physaliferous cells

ANS D Explanation:Diagnosis of Hodgkin's disease rests on the pathologic finding of the Reed Sternberg cells, which are multinucleated giant cells.

200

The incidence of breast cancer is highest in developed nations with the exception of (A) France (B) England (C) Japan (D) Australia

ANS C The incidence of breast cancer is high in all of the most highly developed regions except Japan, including the United States and Canada, Australia, and Northern and Western Europe, ranging from 82.5 to 99.4 per 100,000 women per year. (See Schwartz 9th ed., Chapter 10, Oncology.)

300

You admit a 69-year-old man for resection of squamous cell carcinoma of the lung. Laboratories demonstrate a serum calcium level of 16. Which of the following will not lower the calcium level? (A) gallium nitrate (B) calcitonin (C) furosemide (D) hydrochlorothiazide (E) bisphosphonates

ANS D Inhibition of bone resorption can be achieved with gallium nitrate, calcitonin, and bisphosphonates. Bisphosphonates are highly effective in inhibiting osteoclast activity in the bones. Action of onset is delayed for 3–4 days, so a more immediate acting agent is usually administered. Calcitonin is also a potent inhibitor of osteoclast activity. Its effect on serum calcium levels occurs within hours of administration, so it is often combined with bisphosphonates. Its effect is transient. Tachyphylaxis develops in 2–3 days. Lasix increases the renal excretion of calcium. Hydochlorothiazide, on the other hand, increases tubular reabsorption of calcium in the distal tubule and can cause hypercalcemia.

400

Li-Fraumeni's syndrome is associated with all of the following except: (A) early onset breast cancer (B) p53 mutation (C) leukemia (D) chromosome 13 mutation (E) sarcoma

ANS D Li-Fraumeni's syndrome is an autosomal dominate disease that was first documented in families whose children had sarcomas. Relatives were also found to have an increased number of early onset breast cancer, leukemia, osteosarcoma, brain tumors, and adrenocortical tumors. It is estimated that 45% of women with this mutation will develop breast cancer before the age of 60. Over 75% of these women develop breast cancer between the ages of 22 and 45 years. Interestingly, the affected males do not appear to have an increased risk of breast cancer. The genetic defect only accounts for 1% of all breast cancers. It is associated with a p53 mutation located on chromosome 17.

500

Which of the following is thought to have contributed to a decrease in the worldwide mortality rate of gastric cancer? (A) Lower intake of fruits (B) Better food preservation (C) Routine laboratory monitoring (D) More effective therapy after diagnosis

ANS B The incidence of stomach cancer varies significantly among different regions of the world. The age-adjusted incidence is highest in Japan (62.1 per 100,000 men, 26.1 per 100,000 women). In comparison, the rates are much lower in North America (7.4 per 100,000 (4.4 to 3.4 per 100,000 men, 2.5 to 3.6 per 100,000 women). The difference in risk by country is presumed to be primarily due to differences in dietary factors. The risk is increased by high consumption of preserved salted foods such as meats and pickles, and decreased by high intake of fruits and vegetables. There also is some international variation in the incidence of infection with Helicobacter pylori, which is known to play a major role in gastric cancer development. Fortunately, a steady decline is being observed in the incidence and mortality rates of gastric cancer. This may be related to improvements in preservation and storage of foods as well as due to changes in the prevalence of H. pylori. (See Schwartz 9th ed., Chapter 10, Oncology.)