Colon Carcinoma

Question 1

Aetiology

Answer 1

• red/processed meat
• alcohol
• smoking
• obesity
• increasing age (>50)
• pre-existing adenomatous polyp
• ulcerative colitis for more than 10 years
• familial adenomatous polyposis
• hereditary non-polyposis colon cancer
• family history

Amsterdam criteria

• at least 3 relatives with histologically confirmed colorectal cancer
• at least 2 successive generation involved
• at least 1 of the cancer diagnosed before age of 50

Question 2

Pathology

Answer 2

APC pathway (adenoma-carcinoma sequence)/ chromosomal instability pathway

• loss of APC suppressor gene on 5q21
• beta-catenin accumulate and activate transcription gene (MYC and cyclin D1)–> promote cell proliferation
• K-RAS (12p12) mutation
• loss of tumour suppressor gene at 18q21 (SMAD2 and SMAD4)
• loss of p53 (17p13)
• localised epithelial proliferation–> small adenoma–> large adenoma–> more dysplastic adenoma–> carcinoma in-situ–> invasive cancer

Defect in DNA mismatch repair/ microsatellite instabiliity

• mutation in one of 5 DNA mismatch repair gene (MSH2, MSH6, MLH1, PMS1, PMS2)–> deficiency in ability to repair mismatched base pair in DNA–> HNPCC
• loss of DNA mismatch repair gene–> microsatellite instability (BAX gene and type II TGF-beta receptor)
• better prognosis

Question 3

Mode of spread

Answer 3

• direct extension: adjacent viscera (small intestine, stomach, duodenum, ureter, bladder, uterus, abdominal wall)
• lymphatic: paracolic nodes–> para-aortic node, via thoracic duct–> supraclavicular nodes
• haematogenous: liver via portal vein, lung
• transcoelomic: carcinomatous peritonei (via subperitoneal lymphatic or viable tumour cells shed from serosal surface), malignant ascites