Neoplasia Flashcards
Neoplasia
‘Any new autonomous growth (independent of growth)
New growth’
Classification of neoplasms
A. Benign (oma): 1. Epithelial Papilloma, adenoma 2. Mesenchymal B. Malignant: 1. Epithelial Carcinoma 2. Mesenchymal Sarcoma
Papilloma
- Finger like projections with fibrovascular core
2. Adenoma : tumour of a gland
Exceptions of nomenclature of neoplasms
Malignancies like:
Seminoma, lymphoma, chordoma, chloroma, melanoma
Mixed tumours
1. Single germ layer Pleomorphic adenoma 2. More than one germ layer Teratoma: A. Cystic/ dermoid cyst B. Mature teratoma: benign C. Immature teratoma: malignant
Choriostoma
Normal tissue in abnormal location (Ectopic crest of normal tissue)
Not a neoplasm or cancer
Hamartoma
Abnormal tissue in normal location
The abnormal tissue is disorganised/ haphazard
Eg., pulmonary hamartoma
Recently, it is discovered that they show clonal chromosomal rearrangements and therefore can be considered as tumours
Anaplasia
Hallmark of malignancy
Lack of differentiation 1. Pleomorphism is seen (variation in shape and size of cells) 2. High N/C ratio of 1:1 (instead of (1:4-1:6) 3. Hyperchromatic nuclei 4. Prominent nucleoli 5. Loss of polarity 6. Abnormal mitosis Seen in malignant tumour, not in benign
Molecular basis of cancer, or Hallmarks of cancer
- Self sufficiency in growth signals (oncogenes)
- Insensitivity to growth inhibitory signals (tumour suppressor genes)
- Evasion of apoptosis
- Limitless replicative potential
- Sustained angiogenesis
- Invasion and metastasis
- Altered cellular metabolism
- Escape of immune recognition
Protooncogenes
- Growth factors
- Growth factor receptor
- Signal transduction proteins
- Nuclear transcription factors
- Cyclins and CDKs
Examples of growth factors leading to cancers
- sis (PDGF-β) ➡️ astrocytoma
- Hepatocyte GF ➡️ Hepatocellular carcinoma HCC
- HST-1 ➡️ osteosarcoma
Their overexpression leads to these cancers
Examples of growth factor receptor that leads to cancer
- C-kit (CD-117) ➡️ GIST via point mutation
Via overexpression of EGFR: - EGFR-1 (ERB-1) ➡️ adenocarcinoma
- EGFR-2 (ERB-2) ➡️ breast and ovarian cancer
- RET ➡️ Medullary carcinoma of thyroid and MEN-2 syndrome via point mutation
- ALK➡️ various cancers
Loss of function mutation in RET leads to
Hirshsprung’s disease
ALK gene and cancer
Anaplastic lymphoma kinase gene of chromosome 2 Gene for a growth factor receptor Mutation leads to: 1. ALCL (anaplastic large cell lymphoma) 2. Inflammatory myofibroblastic tumours 3. Adenocarcinoma of lung
Signal transduction proteins leading to cancer
- ABL ➡️ CML, ALL
- RAS (most common oncogene mutated in human malignancy)
- BRAF V600
- NOTCH ➡️ ALL
ABL as protooncogene
ABL (9th chromosome) undergoes translocation with BCR t(9:22) ➡️ bcr:abl fusion transcript ➡️constitutive activation of tyrosine kinase ➡️ leukaemia :
- P210 kDa➡️ CML or
- P190 kDa ➡️ ALL (poor prognosis)
RSA as protooncogenes
Point mutation of RSA➡️
GAPs (GTPase activation proteins become ineffective ➡️
GTP RAS not inactivated to GDP RAS ➡️
cancer
Cancers caused by RAS gene mutation
Most common oncogene mutated in human malignancy
K. K-RAS ➡️ colon, pancreas, lung cancer
H. H-RAS ➡️ bladder/ kidney tumours
N. N-RAS ➡️ melanoma
Cancers caused by BRAF V600 mutation
P. Papillary carcinoma of thyroid L. Langhan’s cell histiocytosis A. Astrocytoma C. Colon cancer H. Hairy cell leukaemia
Nuclear transcriptions factors leading to cancers
myc oncogene
3 types:
L. L-myc➡️ small cell carcinoma of lung (via amplification)
N. N-myc ➡️ neuroblastoma (via amplification)
C. C-myc ➡️ Burkit’s lymphoma (via t(8:14)
Cyclins and CDKs leading to cancers
Mantle cell lymphoma
t(11:14) ➡️ leads to overexpression of cyclin D ➡️ cell proliferation continues
11 chromosome ➡️ cyclin D
14 chromosome ➡️ IgH
Rb gene
Gene on chromosome 13q14 Governor of cell cycle Regulated G1-S transition Rb two forms: 1. hypophosphorylated ➡️ active 2. hyperphosphorylated ➡️ inactive Mutation of Rb leads to: 1. Retinoblastoma 2. Osteosarcoma
Knudson’s two hit hypothesis
Loss of heterozygosity
Both alleles of Rb must be mutated for retinoblastoma Rb to develop
In familial Rb, 1 copy of mutated allele by birth, 2nd by mutation after birth
Thus ‘Loss of heterozygosity’ occurs
p53
Properties
Gene in chromosome 17p
Mutation of p53 ➡️ Difraumeni syndrome (autosomal dominant)
Guardian of genome/ molecular policeman of cell
Mutation in >50% of malignancy
Functions of p53
- Induces p21 ➡️ CDK inhibitor ➡️ cell cycle arrest
- GAF 45 ➡️ repair cells ➡️ re enter cell cycle, if this fails ➡️
- Activates pro apoptotic factor BAX, BAK ➡️ apoptosis
Examples of chemical carcinogens
Polycyclic aromatic hydrocarbons (PAH) Aflatoxin Arsenic Asbestos PVC Diethyl stilbestrol Benzene β-Naphthylamine/azo dyes
Polycyclic hydrocarbons cause
Aflatoxin causes
Bronchogenic cancers
Hepato Cellular Carcinoma
Arsenic causes
Asbestos causes
Skin cancer, lung cancer
Lung cancer (adenocarcinoma), malignant mesothelioma
Polyvinyl chloride PVC causes
Diethyl stilbesterol causes
Cadmium causes
Hepatic angiosarcoma
Vaginal cancer
Prostate cancer
Benzene causes
β-Naphthylamines/azo dyes of dry cleaning causes
Leukaemia
Bladder cancer