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CH 41 KIDNEY CA > BIOLOGY OF RENAL CELL CARCINOMA > Flashcards

BIOLOGY OF RENAL CELL CARCINOMA Flashcards

1
Q

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

A

CORTEX

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2
Q

What is the most common subtype of RCC?

A

ccRCC

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3
Q

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

A

75-85%

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4
Q

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

A

ccRCC

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5
Q

What type of gene is commonly lost in ccRCC?

A

pVHL gene

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6
Q

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

A

proximal tubular epithelium

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7
Q

What are the 3 histomorphologic subtypes of RCC?

A
  1. ccRCC (CLEAR CELL)
  2. pRCC (PAPILLARY TYPE 1 & 2)
  3. chRCC (CHROMOPHOBE)
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8
Q

What subtype constitute 10-20% of RCC?

A

PAPILLARY TYPES 1&2

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9
Q

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

A

CHROMOPHOBE

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10
Q

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

A

HIF−hypoxia pathway

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11
Q

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

A
  1. Warburg effect (aerobic glycolysis) 2. arginine synthetic abnormalities (due to arginosuccinate synthetase-1 [ASS1] deficiency)
  2. Glutamine pathway reprogramming
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12
Q

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

A

immune checkpoint inhibitors

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13
Q

What 5 metabolic pathways are upregulated in ccRCC?

A
  1. aerobic glycolysis
  2. carnitine and lipid synthesis
  3. reductive carboxylation
  4. glutathione oxidized glutathione (GSH/GSSG) pathway
  5. tryptophan metabolism
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14
Q

What 2 metabolic pathways are downregulated in ccRCC?

A
  1. UREA CYCLE
  2. TCA CYCLE
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15
Q

What is the pathology in RCC?

A

METABOLIC REPROGRAMMING

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16
Q

What are the 3 genetic abnormalities in ccRCC?

A

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

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17
Q

What are comprise the majorityof ccRCC cases?

A

SPORADIC

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18
Q

What % of ccRCC is linked to Hereditary diseases?

A

2-3%

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19
Q

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

A

VHL gene

20
Q

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

A

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

21
Q

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

A

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

22
Q

What are the epigenetic regulator genes?

A
  1. polybromo 1 (PBRM1)
  2. BRCA-associated protein-1(BAP1)
  3. SET domain–containing 1 (SETD1)
23
Q

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

A

PTEN DEFICIENCY

24
Q

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

A

mTOR PATHWAY PROTEINS

25
Q

What are the 4 mTOR pathway proteins?

A
  1. PTEN
  2. AKT
  3. PIK3CA
  4. mTOR
26
Q

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

A

pRCC

27
Q

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

A

TYPE 1

28
Q

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

A

TYPE 2

29
Q

What type of pRCC portends a worse prognosis?

A

TYPE 2

30
Q

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

A

COLLECTING DUCT

31
Q

What RCC is similar to benign oncocytomas?

A

chRCC

32
Q

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?

A

chRCC

33
Q

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

A

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

34
Q

ChRCC is more common in what population?

A

YOUNGER FEMALES

35
Q

What is the least aggressive of all RCC types?

A

chRCC

36
Q

What is the clinical presentation of RCC?

A

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

37
Q

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

A

25%

38
Q

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

A

50%

39
Q

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

A

Hypercalcemia

40
Q

RCC typically presents at what age group?

A

60 to 70 years

41
Q

What are the 5 risk factors for RCC?

A
  1. male gender
  2. obesity
  3. tobacco use
  4. DM
  5. HTN
42
Q

What population tends to have better survival in RCC?

A

OBESE
(protective effect of brown fat)

43
Q

What lowers RCC risk?

A

alcohol exposure

44
Q

What 2 factors predispose ESKD patients to develop RCC?

A
  1. Cystic disease
  2. prolonged dialysis dependency
45
Q

What is the risk of ESKD patients to develop RCC?

A

100-fold increased risk

CH 41 KIDNEY CA (9 decks)

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