Intestinal adenocarcinoma

1. Intestinal
adenocarcinoma
Jake Prins and Sebastiaan van Jole
week 7

2. Intestinal adenocarcinoma
• Anatomy of the colon
• Dysplasia and polyps
• Major pathway
• Prognostic values
• Risk factors
• Signs and symptoms

3. Gross anatomy

4. Microscopic
Transverse Section

5. Microscopic
longitudinal section

6. healthy colon

7. dysplasia
in situ
carcinoma
No differentiation
Lots of chromatin
Lots of mitosis
Change cell size
Change cell form
No degradation of
basement membrane

8. • Raised protrusions of colonic mucosa
• 2 most common types:
• hyperplastic
• adenomatous
Colonic polyps

9. Hyperplastic polyp
• Most common
type
• Due to hyperplasia
of the glands
• Benign and no
malignant potential

10. Adenomatous polyp
• 2nd most common type
• Neoplastic proliferation
of glands
• Benign, but premalignant

11. 2 major pathways
• Adenoma-carcinoma sequence
• Microsatellite instability because of
mismatch repair: often leads to HNPCC*

12. Adenoma-carcinoma sequence
• Sporadic or inherited APC mutations at chromosome
5q increase risk for formation of polyp.

13. APC mutations

14. Adenoma-carcinoma sequence
• Sporadic or inherited APC mutations at chromosome
5q increase risk for formation of polyp.
• K-ras mutations lead to formation of a polyp

15. Inside a healthy cell
• Cell cycle arrest through p53 activating p21: inhibition
of CDK-1 and CDK-2 stops cell cycle at G1 and S
• DNA repair
• Senescence
• Apoptosis by:
• Inhibition of anti-apoptosis genes, like BCL2
• Activation of pro-apoptosis genes, like Bax

16. BAX
• Release of cytochrome C
• Activation of Apaf-1
• Activation of procaspase 9
• Activation of procaspase 3, 6, 7
• Caspases cleave protein
substrates and initiate apoptosis

17. Adenoma-carcinoma sequence
• Sporadic or inherited APC mutations at chromosome
5q increase risk for formation of polyp
• K-ras mutations lead to formation of a polyp
• P53 mutations and upregulation of COX-2

18. Adenoma-carcinoma sequence
• We try to detect polyps as early as possible
• Goal is to remove polyps before they progress to
carcinoma.

19. • Invasion of
submucosa
• Sessile growth
Prognostic values

20. • Invasion of
submucosa
• Sessile growth
• Villous histology
• CEA >5.5 ng/ml
Prognostic values
Tubular:
5-10% risk
Villous:
50% risk

21. • Familial Adenopolyposis: Autosomal dominant
• Gardner syndrome: FAP, fibromatosis, osteomas
• Turcot syndrome: FAP, CNS tumors
• Juvenile polyposis
• Peutz-Jeghers syndrome: Polyps throughout GI,
Hyperpigmentation on lips, oral mucosa, genitals
• HNPCC: Also higher risk of ovarian and endometrial
carcinoma
• Ulcerative colitis: Because of chronic inflammation
Risk factors: Age

22. • Usually clinically silent
• Might bleed
• Right sided: Iron deficiency anemia, Pain (HNPCC)
• Left sided: Blood, Small stool (FAP)
• Fatigue
• Cachexia: weight loss
Signs and symptoms