Question 6#

The loss of function of the VHL protein in renal cell carcinoma is mediated by which of the following? 

A. Bcl-2

Answer B

Hypoxia inducible factors are transcription factors that respond to a decrease in oxygen levels on the cellular environment. Inactivation of the VHL protein leads to upregulation of HIF-2 alpha, which in turn leads to upregulation of VEGF, erythropoietin and PEGF. VEGF binds to a tyrosine kinase enzyme (VEGFR-2) on endothelial cells promoting tumour angiogenesis.

Question 7#

Which of the following is the CORRECT sequence of steps in a classical haematological metastatic process?

A. Growth, Extravasation & Migration, Arrest, Survival, Intravasation

Answer C

The steps of the metastatic process are:

1. Intravasation – The movement of cells into the blood stream.
2. Arrest – Cancer cells are larger than most capillaries and hence lodge themselves within the capillaries resulting in arrest.
3. Extravasation & Migration – Some cells die at the arrest stage but others will pass out of the endothelium into tissue due to the action of cell adhesion molecules, extracellular matrix, growth factors and chemokines.
4. Survival & Growth – The survival and growth of tumour cells once they are within a particular organ is entirely due to the environment within the organ itself and to the particular tumour cell. Cell-cell, cell-matrix, and growth factor interactions are required for malignant cells to survive and for tumour cells to grow and produce metastatic lesions.

Question 8#

Regarding the following table, which of the following is FALSE?

A. Sensitivity = w/(w + y)

Answer D

The negative predictive value is calculated as z/(y + z).

The screen positive rate can be calculated as (w + x ) /(w + x + y + z).

Question 9#

Regarding the major histocompatability complex (MHC), which of following is FALSE?

A. MHC Class I molecules are associated with a light chain, beta-2 microglobulin

Answer B

MHC are genes that are found on DNA that code for proteins such as the MHC molecules. T lymphocytes recognise antigens, including tumour antigens, which are bound to MHC molecules on antigen presenting cells.

There are three classes of MHC molecules, I, II and III.

MHC Class I molecules are made up of transmembrane heavy chains (alpha 1, 2 and 3 domains) associated with a light chain, beta-2 microglobulin.

MHC Class II molecules are made of two transmembrane heavy chains each containing two domains, alpha 1/alpha 2 and beta 1/beta 2.

MHC Class III proteins include components of the complement system such as cytokines.

Question 10#

Which of the following immunohistochemical features would be associated with an aggressive tumour in bladder cancer?

A. Low p53

Answer D

Retinoblastoma (Rb) protein is a tumour suppressor protein, which is involved in preventing excessive cell growth by inhibiting the cell cycle until the point where the cell is ready to divide. At the point of cell division, it is phosphorylated rendering it inactive. p53 is a gene that codes for a protein that regulates the cell cycle and apoptosis. Defective p53 allows abnormal cells to proliferate and lead to cancer. Ki67 is a cellular marker for proliferation, which is associated with ribosomal RNA transcription. Inactivation of Ki67 leads to inhibition of ribosomal RNA synthesis. Increased expression is associated with aggressive pathological features. E-cadherin is a cell adhesion molecule that is involved in adherent junction formation, which allow cells to bind to one another. Decreased expression is associated with increased metastasis.