Metastatic Cancer – Gross Pathology Lymph node - metastasis from breastLiver – metastasis from lung Vertebral column – metastasis from prostate Mesentery – metastasis from colon

Biology of Tumour Growth Kinetics of Tumour Cell Growth –Ki-67 Tumour Angiogenesis –FVIII, CD31 Tumour Progression and Heterogeneity –Mutation of tumour suppressor genes p53 Mechanisms of Invasion and Metastasis: –E-cadherin CD 34 p53

Laboratory Diagnosis of Cancer Cytologic and Histologic Methods Electron microscopy Immunocytochemistry Molecular Diagnosis Flow Cytometry Tumour Markers

Cytologic & Histologic Methods Excision or biopsy –Routine or Special Fixatives –Frozen Section (“Quick section”) Needle aspiration –FNA - breast, thyroid, lymph nodes, prostate, deep seated structures Cytologic smears – Pap smears –Brushings – cervix, endometrium, endoscopic (bronchoscopic, gastrointestinal) –Washings and fluids – abdominal and pleural cavities, urine, blood, CSF

Immunocytochemistry Categorization of undifferentiated malignant tumours –Carcinoma vs. lymphoma vs. melanoma vs. sarcoma Categorization of leukemias and lymphomas –Tumours arising from T & B lymphocytes and from mononuclear-phagocytic cells Determination of site of origin of metastatic tumours –PSA, thyroglobulin

Immunocytochemistry (2) Detection of molecules that have prognostic or therapeutic significance –Hormone receptors – estrogen & progesterone –Protein products of oncogenes – c-erbB2 Etiology and functionality of tumours –Viruses – e.g. HBV –Protein products – e.g. ACTH, immunoglobulins Biology of tumour growth –Kinetics of cell growth - Ki-67 antigen –Tumour angiogenesis – CD31, FVIII related Ag

Tumour Markers Biochemical indicators of the presence of a tumour Include: cell surface antigens, cytoplasmic proteins, enzymes, hormones Detected in plasma or other body fluid Cannot be construed as primary modalities for the diagnosis of cancer

Tumour Markers Hormones –Human chorionic gonadotrophin –Calcitonin –Ectopic Oncofetal Antigens –Alpha-fetoprotein –Carcinoembryonic antigen Isoenzymes –Prostatic acid phosphatase –Neuron specific enolase Specific proteins –Immunoglobulins –Prostate-specific antigen Mucins & other glycoproteins –CA-125 (ovarian ca) –CA-19-9 (colon ca)

Grading and Staging of Tumours Grading – based on the degree of differentiation of the tumour cells and the number of mitoses within the tumour –Correlates with the tumour ’ s aggressiveness Staging – based on –Size of the primary lesion –Its extent of spread to regional lymph nodes, –Presence or absence of blood-borne metastases

TNM Staging System Varies for each specific form of cancer T = size of primary tumour –T1 to T4; T0 for in situ (non-invasive) tumours N = regional lymph node involvement –N1 – N3 – increasing number & range of nodes M = metastases –M0 – no distant metastases –M1 or M2 – presence of blood-borne metastases and some judgment as to their number

Case Presentation – Breast Cancer A 49 year old peri- menopausal woman visited her doctor for evaluation of a lump that she felt in her right breast. Five years previously, the patient had a biopsy of her left breast (photos).

Physical Findings A non-tender, slightly moveable, 2.0 cm mass palpable in the upper outer quadrant of the right breast. Several smaller nodules and ill-defined firm areas are palpable in both breasts. The nipple and skin are unremarkable. The lower right axilla contains a 1.5 cm moveable nodule.