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53 Cards in this Set
- Front
- Back
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Oral cancer |
Squamous cell carcinoma (involves epithelial cells)
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LCM and analysis (3 methods)
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Use LCM (tiny laser) to isolate cancer cells; Then 1) amplify/analyze RNA to see which genes are up and down regulated (compared to normal RNA), 2) Western blotting to look at protein differences between tumor cells and normal cells, and/or 3) Gene arrays to analyze DNA (Each box contains a specific gene – you can tell which gene is up or down regulated depending on what color the box is shining)
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How many divisions can normal vs cancer cells undergo?
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NORMAL: up to 55 cell divisions before they senesce due to shortening of telomeres; CANCER CELLS: immortal; if you keep supplying them with nutrients they will go on dividing forever; Due to ACTIVATED TELOMERASE in cancer cells allow for this
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How do cancer cells Enhance their supply of oxygen and nutrients
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promoting the formation of new blood vessels
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Clonal expansion in cancer cells
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allows them to acquire more mutations that will let them survive (via angiogenesis, escaping immunity, ability to migrate/invade/metastasize)
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Normal cell cycle (5 phases)
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1) G0 – no proliferation, 2) G1 - between M (mitosis) and next S phase (chromosome duplication); centromere duplication and growth in mass, 3) S phase 4) G2 – After S phase; chromosomes have been duplicated and ready to divide (go to M), 5) M – mitosis
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Normal cells: Plastic/stabile cells vs labile cells
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Plastic/stable are normally in G0 and don’t participate in cell cycle; Labile cells are constantly renewed and participating in cell cycle
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Common mutation in head/neck carcinoma (HNSCC)
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tumor suppressors (p16 and p53) are both inactivated
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Human Papilloma Virus (HPV)
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Has tropism for epithelial cells (attracted to them); Likes to make cells divide since viruses are obligate intracellular organisms and takes over replication
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How does HPV promote cell division /turn the cell into cancer?
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codes for early proteins E6 and E7, which inactivate p53 and p21/Rb (tumor suppressors) to allow host cells to divide; HPV inserts its DNA into host DNA, but E6 and E7 lose control and they’re produced in too high amounts and they turn the host cell into cancer cells (CCs) such as cervical cancer and HNSCC (incl. base of tongue and tonsils)
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p53
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causes either apoptosis or up-regulation of another tumor sup p21
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p21
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inhibit cyclin/CDKs which ultimately tell cells to stop DNA replication so that cells can repair any DNA mutation
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Survival ligands
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In normal cells, Activate a pathway (involving EGFR growth factor receptors) that tells cells to survive, grow, divide, etc.; In HNSCC cancer cells, these receptors or ligands are overexpressed or activated in the absence of ligand
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What does the AKT pathway do?
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Also involve EGFR; promotes growth (Activates NK-kB – prosurvival factor), blocks tumor suppressors (p53, p21, p27 ) and apoptosis (inactivates caspases); Cancer cells get pushed through cycle even though it has mutations and would normally be gotten rid of
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What inactivates the AKT Pathway?
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PTEN (a tumor suppressor)
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How is AKT activated?
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Phosphorylated and antibodies bind
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The NF-κB Pathway
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TNF-a (tumor necrosis factor alpha) pathway where TNF-a binds to TNF receptor 1; Ultimately activates NF-kB to block apoptosis to promote tumor cells
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Significance of pathways
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Can guide in development of personalized medicine
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Biomarkers
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Can help tell you what type of cancer the patient is susceptible to and what type of treatment would be the best for that patient. Proteins, DNA, etc. can all act as biomarkers, esp. in saliva
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Why is HNSCC fatal?
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they are not painful and difficult to find – makes them harder to be caught earlier on
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Oral cancer in men vs women
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Usually found in men because they were traditionally the only group that smoked and drank (2/3 of cases); Found in women populations now though since alcohol/tobacco marketing has been shifted towards females too
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Age affected
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Mostly between 50 and 70
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Initial symptoms of oral cancer
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Erythroplakia (Red plaque; asymptomatic surface lesions with erythema and slight elevation); Poorly differentiated cells and unusually thick layer of keratin
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Leukoplasia
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white plaque; Makes up 1/3 of lesions but only 25% of these lesions are actually cancerous; larger than erythroplakia
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Differential diagnosis
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Aspirin burn or frictional keratosis could be mistaken for Leukoplasia
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Erythroleukoplakia or “speckled leukoplakia”
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Red and white lesions; High chance of being cancerous
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5 Most common sites of oral cancer; Why?
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1) Floor of mouth, 2) Tongue, 3) Soft palate, 4) Anterior tonsillar pillar, 5) Retromolar trigone; Gravity pulls carcinogen-containing SALIVA and foods to those areas and there is NO KERATINIZATION |
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Why is combination of smoking and drinking a major risk factor?
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alcohol solubilizes carcinogens in tobacco
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Symptoms of perineural invasion
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Tender, painful lesions; difficult to surgically remove
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Advanced lesions
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extra thick areas with keratin on top and ulcerated areas leading to red patches; palpable masses and symptoms such as a vague persistent sore throat or ear infection occur; dissemination to ipsilateral submandibular and jugulodigastric nodes is common, and the patient may present with a mass in the neck.
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5 Overall symptoms of oral cancer
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1) COLOR: white, red, or red-white lesion, 2) SWELLING: thickening, rough spot, crust or small eroded area, 3) ULCER: that bleeds easily or does not heal, 4) PAIN: tenderness or numbness anywhere in the mouth or on the lips (perineural invasion), 5) FUNCTION: difficulty in chewing, swallowing, speaking or moving the jaw or tongue, changes in occlusion
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Layers in Normal epithelium (6) |
1) Stratum corneum, 2) Stratum granulosum, 3) Stratum lucidum, 4) Stratum spinosum, 5) Stratum basale, 6) Dermis; * Keratin layer on top, Squamous cells below |
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Reti ridges in oral cancer
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Rete ridges are very bulbous and tear drop shaped; Start to move upwards (dysplasia)
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Effects of inflammation in cancer
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Inflammatory mediators and events can help CCs grow
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Keratin pearls
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Keratin produced in islands of invading cancerous epithelial cells; Found in underlying CT
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How is grading of cancer determined?
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1) CYTOLOGY: Degree of nuclear pleomorphism (variable size and shape of nucleus,), 2) MITOTIC INDEX: How fast the tumor is growing; *Well-differentiated, slow-growing cancers are “Low grade” and poorly differentiated/fast are High grade; Grades go from 1 to 3; HIGH GRADE IS EASIER TO TREAT
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Treating poorly vs well differentiated cancer cells
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Well differentiated cancers produce keratin and such to help it survive so harder to treat
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Treating slow growing vs fast growing cancer cells
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slow growing (well differentiated) cancers are harder to treat with chemo; (Rapid growing tumors are more prone to death by chemo)
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Multiple sites of cancer in the mouth
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Just because you had oral cancer in one part of the mouth and treated it, it doesn’t mean all parts of the mouth is exempt from cancer, esp. if other parts exposed to the same carcinogen (multiple primary cancer sites in 40% of patients)
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Field cancerization effect
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What you’ve done to that whole area will affect whole area equally
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5-year survival rate of oral cancer
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50% (75% survival if detected at early stage and 35% survival if detected at late stage so EARLY DETECTION IMPORTANT)
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2 Viruses involved in HNSCC
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1) Epstein-Barr virus (EBV): nasopharyngeal carcinoma, 2) HPV: upper aerodigestive tract tumors. HPV-16 has been isolated in 36% of oral cavity cancers.
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Environmental exposures causing oral cancer |
Radiation (UV light for SCC of the lower lip, or irradiation in cancer therapy), paint fumes, plastic byproducts, wood dust, asbestos, gasoline fumes; *Cancers due to industrial things (paint fumes, wood dust, etc.) Less common now since more precautions taken
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GERD and cancer
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GERD is a significant risk factor for cancer of the larynx and vocal cords
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Chewing vs smoking tobacco
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The risk of oral cancer is higher in smokeless tobacco users over cigarette smoking (the risk of lung cancer is lower); Can also cause gingival recession and mouth sores; It causes constant irritation to the spot in the mouth where the wad of chew is placed and results in permanent damage to the gingiva. The injured tissue pulls away from the teeth and becomes leathery, exposing root surfaces and leaving teeth sensitive to heat and cold (TOBACCO POUCH KERATOSIS)
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Leukoplasia and chewing tobacco
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Chewing tobacco can also cause leukoplasia that is NOT CANCEROUS; Is only cancerous in 3-5% of cases
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Verrucous Carcinoma
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“Snuff-dippers cancer”: a low-grade tumor that generally is considered a clinicopathologic variant of squamous cell carcinoma; Cancer spreads outwards instead of going down into the epithelium but Can become an invasive SCC; distant metastasis is rare
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Appearance of Verrucous Carcinoma |
EARLY LESIONS: white, translucent patches on an erythematous base. They may develop in previous areas of leukoplakia; ADVANCED LESIONS: white cauliflowerlike papillomas with a pebbly surface that may extend and coalesce over large areas of the oral mucosa; *To excise, you would have to remove a large patch of mucosa
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Betel chewing
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People typically chew betel as a quid consisting of nut pieces from an Areca catechu palm mixed with powdered lime (calcium hydroxide) and wrapped in the leaf of the pepper plant Piper betle. Betel is used primarily as a stimulant. Areca nuts contain alkaloids that induce euphoria and raise a person's heart rate and skin temperature
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Effect of Betel chewing
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causes SUBMUCOSA FIBROSIS (a pre-malignant condition that can eventually become SCC); Caused SCC of mucosa to become most common form of cancer in SE countries were nuts are sold (ex: Taiwan); Turns SALIVA RED
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Oral submucous fibrosis
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a chronic, debilitating disease of the oral cavity characterized by inflammation and progressive fibrosis of the submucosal tissues (lamina propria and deeper connective tissues). It results in marked rigidity and an eventual inability to open the mouth. (Lost vestibular depth, CT dense and acellular like a scar, You lose pinkness in soft palate); The buccal mucosa is the most commonly involved site, but any part of the oral cavity can be involved, even the pharynx.
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UV related vs tobacco/alcohol-related oral cancer
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Tobacco us worse; UV: SCC are visible outside the mouth (usually associated with actinic or solar cheilitis) ; Its mutations are easier to treat; TOBACCO: SCC are inside the mouth and hard to see
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HPV related vs tobacco/alcohol-related oral cancer |
HPV (of oropharynx): better because they are poorly differentiated SCC with no keratin/inflammatory cells that grow rapidly; No mutated DNA, just tumor suppressors, esp. p16 |
