20.06.28 Carcinomas

Question 1

What is a carcinoma

Answer 1

Cancer that develops from epithelia cells

Question 2

What are the subtypes of carcinoma

Answer 2

• Adenocarcinoma= glandular origin. e.g. Invasive ductal carcinoma (most common form of BC)
• Hepatocellular carcinoma= form of adenocarcinoma, most common type of liver cancer
• Renal cell carcinoma= a form of adenocarcinoma
• Squamous cell carcinoma. Squamous cell origin (skin, lining of digestive tract)

Question 3

What does carcinoma in situ mean

Answer 3

• Cells that are significantly abnormal but not yet cancer.
• In the same place as the originated and have not yet spread.
• Stage 0

Question 4

Review of renal cell carcinomas

Answer 4

• Arise from proximal tubular epithelium and most common adult renal tumour.
• Commonly associated with deletion of the short arm of Chr 3.
• Present with haematuria, loin pain, weight loss, anaemia, hypertension.
• 5-8% are hereditary
• 2 main subtypes: clear cell (chr3p del and VHL most common) or papillary (activating MET mutations)

Question 5

Review of Von Hippel-Lindau

Answer 5

• AD, LOF mutations in VHL tumour suppressor.
• 1: 35,000
• Malignant renal cell carcinoma (Clear cell) in 35-75% cases. Haemangioblastomas, phaechromocytomas, renal cysts.

Question 6

Review of hereditary papillary renal cell cancer

Answer 6

• AD, GOF mutations in MET (proto-oncogene)

- Papillary RCC, multiple bilateral tumours, family history of RCC. Metastatic potential is low

Question 7

Review of hereditary leiomyomatosis and RCC (HLRCC)

Answer 7

• AD, mutations in Fumarate hydratase enzyme (incloved in Krebs cycle).
• Penetrance for RCC from 10-50%
• Multiple leiomyomas (benign tumours containing smooth muscle tissue), Papillary RCC.

Question 8

Review of Tuberous sclerosis

Answer 8

• AD, LOF mutations in TSC1/2 (tumour suppressors)
• Growth of numerous benign tumours through out the body (skin, brain, kidneys), developmental problems.
  1: 58,000 live births
• Renal tumours in 2-4% cases

Question 9

Review of hereditary paraganglioma/phaeochromocytoma

Answer 9

• AD, mutations in SDHB/C/D, which encode subunits of succinate dehydrogenase complex- involved in Krebs cycle.
• Characterised by growth of benign tumours near nerve cell bunches (ganglia).
• Phaeochromocytoma is a form of paraganglioma that develops in adrenal glands.
• Increased risk of RCC

Question 10

Review of chr 3 translocations

Answer 10

• Balanced chr3 translocations give inherited susceptibility to renal cancer
• Multiple renal cancer genes on 3p, VHL, PBRM1, BAP1, SETD2

Question 11

Examples of adenocarcinomas

Answer 11

• Lung cancer (30-50% of non-small cell LC)
• prostate cancer. NDRG1/ERG fusion
• Pancreatic cancer
• Oesophageal cancer
• Colorectal cancer

Question 12

Review of squamous cell carcinomas (SCC)

Answer 12

• Cancer arising from squamous cells, which are found in out layer of skin and in mucous membranes.
• 30% of LC are squamous cell, mostly due to smoking
• Head and neck SCC (HNSCC) develop in mucous membranes of mouth, nose and throat.
• Can lead to ulcers, bleeding, difficulty swallowing, breathing or enlarged lymph nodes.
• Mutations occur in CDKN2A, FAT1, HRAS, NOTCH1, PIK3CA, PTEN, TP53

Question 13

Review of hepatocellular carcinomas

Answer 13

• 5th most common cancer
• 3rd most cause of death world wide
• Risk factors= Hepatitis b virus (HBV), HCV infection, prolong dietary aflatoxin exposure, alcoholic cirrhosis.

Question 14

Which oncogenic pathways are mainly involved in hepatocellular carcinoma

Answer 14

• Wnt/β-catenin
• Recurrent mutations in CTNNB1, AXN1, TP53 and CDKN2A
• NRF2/KEAP1 pathway.