CBCL 5

Question 1

Ms. Sawaguchi was found to have a metastatic lesion in her tibia as detected by bone x-ray 5 years after her surgery for breast cancer. Which of following events has likely occurred?

Answer 1

Bone lytic lesion

(Breast cancer metastasis tends to make osteolytic lesions.)

Question 2

Ms. Okamoto, a 60-year old woman, was diagnosed with non-small cell lung cancer with brain metastasis. By genetic profiling including mutation analysis and gene expression analysis of the brain metastasis, which of following is most likely to occur in this metastatic tumor?

Answers:

Loss of c-Myc expression

Loss of K-Ras expression

Mutation in p53

Increased PTEN expression

Increased APC expression

Answer 2

Mutation in p53

(Mutations in p53 are most frequently seen in human cancer. Usually, tumor suppressor (APC and PTEN) expression is reduced in tumors, whereas oncogene (Myc and Ras) expression is increased.)

Question 3

Mr. Don is an 18 year-old man who had surgical resection and chemotherapy for primary osteosarcoma in the right femur. Three years later, metastases were found in lungs. Biopsy confirmed the metastatic origin to be osteosarcoma. Which of following is likely the cause of these metastatic tumors?

Answers:

New osteosarcoma occurred somewhere in the body but only lung metastases were found.

Bone marrow cells moved to lungs and became osteosarcoma.

Lung tissues spontaneously gained the characters of osteosarcoma

When the surgery was performed, the lung micro-metastases were already present. They were dormant and chemo-resistant, but gained the ability to grow 3 years later.

Chemotherapy turned lung epithelial cells into osteoblasts and osteosarcoma.

Answer 3

When the surgery was performed, the lung micro-metastases were already present. They were dormant and chemo-resistant, but gained the ability to grow 3 years later.

(Some cancer cells with stem cell-like properties can be resistant to chemotherapy. These cells could be spread as micro-metastases and later gain the ability to grow in the metastasis sites.)

Question 4

What is the use of folinic acid?

Answer 4

restores active folate stores required for DNA/RNA synthesis. Stabilizes the binding of 5-dUMP and thymidylate synthetase, enhancing the activity of fluorouracil.

Question 5

What is angiogenesis?

Answer 5

The new formation of a blood supply to a particular area

Question 6

Where would you expect to find a colon cancer staged as T3N2M1?

Answer 6

Most likely to spread to the liver, lung and peritoneum. It has also spread to the regional lymph nodes.

Question 7

What are the genes that play an important role in the epithelial to mesenchymal transition?

Answer 7

Slug, Snail, Goose-coid, Twist and ZEB-1

Question 8

A 59-year-old man has been suffering prostate cancer for more than one year. He visits your clinic for the follow up. After imaging and pathological analysis, a metastatic lesion is found in his spine. Which of the following events is absolutely required for the metastasis to occur?

Answers:

Decreased angiogenesis

Mutation in KRAS gene

Invasion through the basement membrane

Inactivation of p53

Backflow of arterial blood

Answer 8

Invasion through the basement membrane

(Invasion through the basement membrane is absolutely required for the cancer cell to escape the primary tumor and disseminate to the spine.)

Question 9

In another patient, Mr. Sanderson, was found to have a metastatic lesion in his femur that was detected by bone x-ray 10 years after surgery for prostate cancer. Which of following events has likely occurred?

Answer 9

Bone forming lesion

(Prostate cancer metastasis tends to make osteoblastic lesions or bone forming lesions.)

Question 10

What is fluorouracil?

Answer 10

A pyrimidine analog antimetabolite that interferes with DNA and RNA synthesis; after activation, F-UMP (an active metabolite) is incorporated into RNA to replace uracil and inhibit cell growth; the active metabolite F-dUMP, inhibits thymidylate synthetase, depleting thymidine triphosphate.

Question 11

Mr. Gilson’s hepatocellular carcinoma is T1N0M0, while Mr. Walsh’s hepatocellular carcinoma is T3N1M1. Which of following characteristics has developed in Mr. Walsh’s tumor compared with Mr. Gilson’s tumor.

Answers:

Increased E-cadherin expression

Loss of p53 activity

Greater numbers of cancer stem cells in the tumor

More inflammatory cell invasion in the tumor

Reduced MMP9 expression

Answer 11

Greater # of CSC in the tumor

(Cancer stem cells have enhanced abilities of establishing metastasis.)

Question 12

In a colon cancer staged as T2N0M0, what events in the multistep process of metastasis has occurred?

Answer 12

Transformation and angiogenesis

[T2: Tumor invades muscularis propria]

Question 13

At the time of original surgery, Mr. Sean’s primary rhabdomyosarcoma in the right forearm was 2 cm long. For this tumor to metastasize to the lung, which of following events should absolutely occur?

Answers:

Tumor cells become dormant

Increased expression of N-cadherin

Epithelial to mesenchymal transition

Increased cell-to-cell adhesion

Survival in the blood stream

Answer 13

Survival in the blood stream

(All tumor cells need to survive in the blood stream to metastasize.)

Question 14

A 60-year old woman with Ewing sarcoma was tested for the presence of tumor cells in her blood stream. The test comes back positive. For tumor cells to get into the blood stream, what metastatic step needs to have occurred?

Answer 14

Darn it, Tomoo! It’s freaking intravasation. Don’t make Miles show you up in an email thread again!

(The first step that has to happen for cancer cells to be in the blood is to get out from primary tumors and invade into blood stream (intravasation).

Question 15

A pancreatic cancer with peritoneal invasion was found in Mr. Grier. Unfortunately, chemotherapy and radiation therapies were not effective. What could you do for Mr. Grier.

Answers:

Perform angio CT

Increase the doses of chemotherapy drugs

Perform surgical resection

Perform genetic profiling of the tumor to identify molecular targeted therapies

Recommend taking natural products that could suppress cancer growth.

Answer 15

Perform genetic profiling of the tumor to identify molecular targeted therapies

(Genetic profiling could reveal a mutation or gene expression pattern in the tumor that may allow using a protein-targeted cancer therapy such as an anti-EGFR antibody or a specific kinase inhibitor.)

Question 16

Would an anti-EGFR drug be useful in treating patients that have a mutation in BRAF or KRAS?

Answer 16

Both patients have mutations that are downstream of the receptor, so an antibody to the receptor would provide little help for the patient. These are ligand independent mutations

Question 17

Many ovarian cancer cells reach the lungs following entering blood stream. However, the majority of the cells cannot grow and establish lung metastases. Which of following is likely the major reason for this observation?

Answers:

Tumor cell death due to high blood flow in the lung

Lung tissue environment is not suited for ovarian cancer cells.

Tumor cell death due to loss of nutrition in the lung

Lung epithelial cells suppress ovarian cancer cell growth.

Ovarian cancer cells can only survive in the ovary.

Answer 17

Lung tissue environment is not suited for ovarian cancer cells.

(Seed and soil theory.)

Question 18

A woman with breast cancer subsequently develops metastases in her vertebral column. The most direct route for spread of the tumor to the vertebral column was via:

Answers:

Intercostal nerves

Branches of the intercostal veins

Local invasion to the vertebrate

Lymphatic vessels draining into the axilla

Invasion into spinal canal and subsequently to the vertebral column

Answer 18

Branches of the intercostal veins

(The most direct way for the cancer to spread to the vertebral column is through the venous system. The most likely route is through the intercostal veins, i.e. hematogenous spread. Lymphatic vessels may carry some tumor cells to the axillary lymph nodes and may participate in the spread of the cancer, but this isn’t the best answer.)

Question 19

What is extravasation?

Answer 19

Leaving the blood source and entering surrounding parenchyma

Question 20

Mr. Hunks was diagnosed with hepatocellular carcinoma. Multiple intrahepatic metastases are found in the right lobes. What is the likely route for the primary tumors to form metastases?

Answers:

Local invasion

Splenic vein

Lymphatic vessels

Portal vein

Inferior vena cava

Answer 20

Portal vein

(The intrahepatic metastasis of hepatocellular metastasis could occur via portal vein or bile duct. Splenic vein is used to metastasis to the spleen, while Inferior vena cava is used for pulmonary metastasis.)

Question 21

Ms. Thompson was diagnosed as triple negative breast cancer with lymph node metastasis. Pathological examination of a metastatic lesion revealed that a majority of the cells displayed a syncytial growth pattern, pushing borders, elevated mitotic activity, atypia with scant cytoplasm, and metaplastic elements (squamous cells, spindle cells). It was noted that regions of tumor have cells with a lower mitotic index and a more organized nuclear structure. Which theory can explain this tumor heterogeneity?

Answer 21

Cancer Stem Cell

(Cancer stem cell theory can explain that some are more differentiated and others remain undifferentiated. CSCs can self-renew and also generate differentiated cells.)

Question 22

In your oncology clinic, you have two patients who are current smokers with lung metastases; one of the patient’s primary tumor started in the bladder while the other patient’s primary tumor started in the breast. Why do both metastasize to the lung?

Answer 22

Lungs have extensive capillary beds

(Capillaries are very thin walled blood vessels and allow easier infiltration of the cancer cell into the lung.)

Question 23

What are the components of FOLFOX?

Answer 23

FOLinic acid, Fluorouracil, and OXaliplatin

Question 24

Genetic and RNA profiling analyses of a tumor from a breast cancer patient revealed reduced expression of cell adhesion protein E-cadherin. Which of the following events does the reduction in E-cadherin will promote?

Answer 24

Metastasis

(Loss of E-cadherin reduces adhesion between tumor cells allowing for dissemination and metastatic occurrence.)

Question 25

Ms. Sage is a 20-year old woman. She was diagnosed as Ewing sarcoma in the right humerus. Despite radical surgery and intensive chemotherapy, lung metastases were found 7 years later. Where does this metastatic Ewing sarcoma likely come from? ## Footnote Answers: Lung cancer had epithelial to mesenchymal transition to become Ewing sarcoma. Micro-metastases in the lung were not killed by chemotherapy and recurred 7 years later. Cancer cells moved to lungs during surgery and grew slowly in the lung. Mesenchymal cells in the lung transformed to Ewing sarcoma during 7 years. A new Ewing sarcoma developed in the lung.

Answer 25

Micro-metastases in the lung were not killed by chemotherapy and recurred 7 years later. (Chemotherapy is used to treat potentially present micro-metastases. However, some of them with cancer stem cell-like properties can be resistant to the chemotherapy.)

Question 26

The CTC assay performed on Mrs. Jones shows a high number of cancer cells to be present in circulation. However, the majority of them cannot survive in the blood stream. Which of following is the major reason for it? Answers: Cancer cell death in the blood stream due to loss of hypoxic environment Cancer cell death in the blood stream due to loss of anchorage Cancer cell death in the blood stream due to loss of nutrition Cancer cell death in the blood stream due to loss of p53 Cancer cell death in the blood stream due to loss of E-cadherin

Answer 26

Cancer cell death in the blood stream due to loss of anchorage (Loss of anchorage causes anoikis (anchorage-dependent cell death) which significantly reduce viable cells in the blood stream.)

Question 27

Where would you expect to find a colon cancer stages as T2N0M0?

Answer 27

In the colon

Question 28

A 45-year-old Caucasian female presented with a rapidly changing "black mole" on her left leg. Initially it was a flat brownish macule, which she had for many years. The patient reported that the lesion had become slightly raised with irregular borders over a period of 4 weeks prior to her presentation. Skin examination showed an 8 mm × 10 mm irregularly shaped two-toned brown papule with ill-defined light brown to pink medial and lower borders, and a dark-brown central area localized to the calf of the left leg. Regional lymph nodes were palpable and node biopsy showed the presence of melanoma cells. Which new function has allowed the melanoma cell to invade through the basement membrane and metastasize to the lymph node? Answers: Increased expression of mTOR Expression of extracellular proteases Inactivating mutations in p53 Decreased expression of CDK inhibitors Expression of secreted cytokines

Answer 28

Expression of extracellular proteases (For the tumor cell to move through the basement membrane, the cell needs to produce extracellular proteases to cleave collagens and other extracellular proteins that compose the basement membrane.)

Question 29

Brain cancer does not usually form distant metastasis, but rather invades into tissues near the tumor. Which of following is considered to be a major factor influencing cancer cell invasion? ## Footnote Answers: Exosome production Specific chemokine receptor expression on cancer cells Reorganization of actin cytoskeleton Expression of extracellular proteases Loss of E-cadherin expression

Answer 29

Expression of extracellular proteases (Expression of extracellular proteases accelerate cancer invasion. Actin cytoskeleton reorganization is important for cell migration/motility, while loss of E-cadherin expression promotes detachment/dissociation of cancer cells from primary tumors.)

Question 30

Mr. Shrikumar was diagnosed as metastatic pancreatic cancer (T2N1M1). For the cancer cells to metastasize to lymph nodes and the liver, which of following changes could occur in the primary tumor? Answers: Decreased MMP9 expression Decreased expression of transcription factors, Snail and Twist Loss of baso-apical polarity Increased cell-cell junctions Decreased ability of cancer cell migration

Answer 30

Loss of baso-apical polarity (Loss of baso-apical polarity is one of features of EMT.)

Question 31

Genetic profiling was performed on colon tumor tissue from Ms. Smith and Ms. Xu. Ms. Smith’s tumor occurred on the left sided colon with no metastasis, whereas Ms. Xu’s tumor occurred on the right side with liver metastasis. Which of following change is most likely to be found in Ms. Xu’s tumor? ## Footnote Answers: Mutation in BRAF Gain of E-cadherin Chromosomal instability Mutation in KRAS Loss of p53

Answer 31

Mutation in BRAF (Colon cancer on the right side tends to have BRAF mutations with high metastatic potential.)

Question 32

For a cancer stages as T3N2M1, what events in the multistep process of metastasis has occurred?

Answer 32

Everything in the picture Automatically stage IV b/c it has metastasized

Question 33

What is oxaliplatin?

Answer 33

a platinum derivative, is an alkylating agent. Following intracellular hydrolysis, the platinum compound binds to DNA forming cross-links which inhibit DNA replication and transcription, resulting in cell death.

Question 34

Mr. Johnson, a 69-year old man, was diagnosed with prostate cancer by biopsy. Also, an unusual sclerotic lesion was found by abdominal X-ray in the patient’s lumbar spine. What do you expect to detect by the following examination? ## Footnote Answers: No signal by bone scan No detectable nodule by MRI Osteoporosis lesion by tumor biopsy Increased serum alkaline phosphatase Increased cholesterol level

Answer 34

Increased serum alkaline phosphatase (When abnormal bone tissue is being formed by cancer cells, levels of alkaline phosphatase increase.)

Question 35

You participated in the care of a patient 5 years ago who received surgical resection of an osteosarcoma in the left tibia. Primary tumors were 5 cm in diameter and tumors were also found in the lungs with calcified lesions. Biopsy confirmed they are metastases of osteosarcoma origin. A regional lymph node metastasis was detected by CT scan. Which of following is appropriate to describe the clinical staging of this patient’s tumor? T1N1M0 T1N1M1a T1N0M1a T2N2M0 T2N1M0

Answer 35

Selected Answer: T1N1M1a

Question 36

Mrs. Jones, a 57-year old woman, has undergone her first round of chemotherapy for breast cancer. Her initial response to her treatment was positive, with significantly reduced primary tumor size. A CellSearch Circulating Tumor Cell (CTC) blood test was performed to show 15 CTCs/ 7.5 ml of blood. Circulating epithelial cells are rare in healthy women (0.1±0.2 CTCs/ 7.5 ml of whole blood). Given this result, which step in the process of metastasis must have occurred in this patient? Answers: Inactivation of p53 Colonization of a distant tissue Cellular quiescence Survival of immune attack Growth of primary tumor to \>10 cm

Answer 36

Survival of immune attack (The first step that has to happen for cancer cells to be in the blood is to survive immune destruction.)

Question 37

A 55-year old man is suffering from pancreatic cancer. For the cancer to spread out over the pancreas, cancer cells need to develop the ability to move through the basement membrane. Which of the following abilities do cancer cells gain to mediate this process?

Answer 37

Expression of extracellular proteases (For the tumor cell to move through the basement membrane, the cell needs to produce extracellular proteases to cleave collagens and other extracellular proteins that compose the basement membrane)

Question 38

A pt with a past history of metastatic colon cancer, was treated with neoadjuctuvant FOLFOX followed by surgical resection and went into remission, and has a cancer in the liver 3 years later. Do you believe this is a new cancer, or is this related to the previous metastatic colon cancer?

Answer 38

This is most likely related to the metatstatic colon cancer. Since there are cancer stem cells that have the ability to "self-renew", these have the capability to metastasize and create tumors at other sites. CSC's are the seeds of the original colon cancer that are capable of evading destruction by chemo and radiation. Then, the liver is a good soil for CSC's from the colon.

Question 39

What is the protein that is used for angiogenesis by tumor cells?

Answer 39

VEGF1