BIOLOGY OF RENAL CELL CARCINOMA

Question 1

RCC is the most common malignancy that originates from which part of the kidney?

Answer 1

CORTEX

Question 2

What is the most common subtype of RCC?

Answer 2

ccRCC

Question 3

How many % does ccRCC comprise among the other histologic subtypes?

Answer 3

75-85%

Question 4

What is the most common and most lethal subtype of RCC?

Answer 4

ccRCC

Question 5

What type of gene is commonly lost in ccRCC?

Answer 5

pVHL gene

Question 6

ccRCC is an aggressive cancer that arises from what part of the nephron?

Answer 6

proximal tubular epithelium

Question 7

What are the 3 histomorphologic subtypes of RCC?

Answer 7

1. ccRCC (CLEAR CELL)
2. pRCC (PAPILLARY TYPE 1 & 2)
3. chRCC (CHROMOPHOBE)

Question 8

What subtype constitute 10-20% of RCC?

Answer 8

PAPILLARY TYPES 1&2

Question 9

What subtype is the least common & constitute 5% of RCC?

Answer 9

CHROMOPHOBE

Question 10

What is the first pathway identified as being altered in ccRCC?

Answer 10

HIF−hypoxia pathway

Question 11

What are the other 4 metabolic abnormalities responsible for paraneoplastic syndromes in RCC?

Answer 11

1. Warburg effect (aerobic glycolysis) 2. arginine synthetic abnormalities (due to arginosuccinate synthetase-1 [ASS1] deficiency)
2. Glutamine pathway reprogramming

Question 12

What is the most recent therapy that has shown considerable promise in treating ccRCC?

Answer 12

immune checkpoint inhibitors

Question 13

What 5 metabolic pathways are upregulated in ccRCC?

Answer 13

1. aerobic glycolysis
2. carnitine and lipid synthesis
3. reductive carboxylation
4. glutathione oxidized glutathione (GSH/GSSG) pathway
5. tryptophan metabolism

Question 14

What 2 metabolic pathways are downregulated in ccRCC?

Answer 14

1. UREA CYCLE
2. TCA CYCLE

Question 15

What is the pathology in RCC?

Answer 15

METABOLIC REPROGRAMMING

Question 16

What are the 3 genetic abnormalities in ccRCC?

Answer 16

1.VHL gene
2. epigenetic regulators and chromatin remodeling genes
3. disruption of PI3K-AKT-mTOR signaling

Question 17

What are comprise the majorityof ccRCC cases?

Answer 17

SPORADIC

Question 18

What % of ccRCC is linked to Hereditary diseases?

Answer 18

2-3%

Question 19

Mutations in this gene are associated with more than 80% of sporadic ccRCC cases?

Answer 19

VHL gene

Question 20

What is the most important function of VHL protein (pVHL)?

Answer 20

polyubiquitination of a variety of proteins, including HIF 1 and 2

Question 21

What is the second most common type of mutation in ccRCC?

Answer 21

epigenetic regulators which are involved in regulation of chromatin maintenance and remodeling

Question 22

What are the epigenetic regulator genes?

Answer 22

1. polybromo 1 (PBRM1)
2. BRCA-associated protein-1(BAP1)
3. SET domain–containing 1 (SETD1)

Question 23

Deficiency of this mTOR pathway protein is associated with more aggressive ccRCC tumors

Answer 23

PTEN DEFICIENCY

Question 24

What proteins are involved in cell proliferation signaling and have been identified in up to 28% of RCC patients?

Answer 24

mTOR PATHWAY PROTEINS

Question 25

What are the 4 mTOR pathway proteins?

Answer 25

1. PTEN 2. AKT 3. PIK3CA 4. mTOR

Question 26

What is the 2nd most common RCC which is also of proximal tubule origin?

Answer 26

pRCC

Question 27

What type of pRCC is characterized by MET proto-oncogene−activating mutations?

Answer 27

TYPE 1

Question 28

What type of pRCC is linked to activation of the NRF2 antioxidant response element pathway as the result of augmented oxidative stress?

Answer 28

TYPE 2

Question 29

What type of pRCC portends a worse prognosis?

Answer 29

TYPE 2

Question 30

chRCC is a rare cancer that originates from which part of the nephron?

Answer 30

COLLECTING DUCT

Question 31

What RCC is similar to benign oncocytomas?

Answer 31

chRCC

Question 32

What type of RCC is linked with whole-chromosome losses and germline mutations in the folliculin gene (FLCN) found in the autosomal dominant Birt-Hogg-Dubé syndrome?

Answer 32

chRCC

Question 33

What is the most frequent mutation in sporadic cases of chRCC?

Answer 33

downregulation of p53 tumor suppressor signaling and loss of function of PTEN leading to PI3K-driven cell proliferation

Question 34

ChRCC is more common in what population?

Answer 34

YOUNGER FEMALES

Question 35

What is the least aggressive of all RCC types?

Answer 35

chRCC

Question 36

What is the clinical presentation of RCC?

Answer 36

occult disease and often present with a late and more advanced stage at the time of diagnosis

Question 37

How many % of patients have metastatic disease or advanced local disease at the time of presentaion?

Answer 37

25%

Question 38

How many % of patients are diagnosed based on incidental findings in abdominal radiologic imaging?

Answer 38

50%

Question 39

What has been identified as a negative prognostic factor for RCC?

Answer 39

Hypercalcemia

Question 40

RCC typically presents at what age group?

Answer 40

60 to 70 years

Question 41

What are the 5 risk factors for RCC?

Answer 41

1. male gender 2. obesity 3. tobacco use 4. DM 5. HTN

Question 42

What population tends to have better survival in RCC?

Answer 42

OBESE (protective effect of brown fat)

Question 43

What lowers RCC risk?

Answer 43

alcohol exposure

Question 44

What 2 factors predispose ESKD patients to develop RCC?

Answer 44

1. Cystic disease 2. prolonged dialysis dependency

Question 45

What is the risk of ESKD patients to develop RCC?

Answer 45

100-fold increased risk