Winter Meeting 2011 - The Pathological Society of Great Britain ...

Detailed Programme – Thursday 6 January 2011
Presenter = P · Abstract numbers are shown in bold and square brackets eg [S123]
16.45–17.00 [PL6] K-ras Mutation is a Negative Prognostic Marker, and Does Not Preclude Benefit From 5-FU
in Stage II/III Colorectal Cancer
P K Southward 1 ; G Hutchins 1 ; K Handley 2 ; L Magill 2 ; C Beaumont 1 ; J Stalhschmidt 3 ;
S Richman 1 ; P Chambers 1 ; M Seymour 4 ; D Kerr 5 ; R Gray 2 ; P Quirke 1
1 Leeds Institute of Molecular Medicine, Leeds, United Kingdom; 2 Birmingham Clinical Trials Unit,
Birmingham, United Kingdom; 3 Histopathology and Molecular Pathology, Leeds, United Kingdom;
4 CRUK Cancer Centre, Leeds, United Kingdom; 5 Sidra Medical and Research Centre, Doha, Qatar
There is currently uncertainty whether the efficacy of 5-FU adjuvant therapy in stage II colorectal cancer is
sufficient to justify the cost and toxicity. Tumour markers that could distinguish patients who will benefit from
adjuvant chemotherapy from those that won’t, or that were strongly associated with disease prognosis, are desirable
both to save money and to avoid treating patients who would derive little or no benefit from chemotherapy.
Mutations of the Kirsten-ras gene occur in 30–40% of sporadic colorectal cancers and are established as clinically
useful predictors of lack of response to EGF receptor targeted treatment in stage IV disease.
We assessed the Kirsten-ras gene as a predictor of response to chemotherapy and risk of recurrence in patients
with stage II/III colorectal cancer randomised between fluorouracil/folinic acid (FUFA) chemotherapy and control
in the Quasar clinical trial. K-ras mutation status was assessed by pyrosequencing for 1583 tumours and was then
correlated to prognosis and treatment benefit from FUFA therapy.
The risk of recurrence for K-ras mutant tumours was significantly higher than that of wildtype: 28% vs 21%
(RR=1.40, 95% CI 1.13-1.74). The proportional increase in risk of recurrence was larger in rectal cancer and in men
but similar in the presence and absence of chemotherapy. K-ras did not predict response to FUFA treatment
K-ras mutation is a useful predictor of recurrence risk in stage II/III colorectal cancer. The greater prognostic value
in rectal cancer and men needs independent confirmation.
17.00–17.15 [PL7] Activating Autophagocytosis Decreases Fat Within the Liver
P A Levene 1 ; H Kudo 1 ; M Thursz 1 ; QM Anstee 2 ; RD Goldin 1
Imperial College Faculty of Medicine at St Mary’s Hospital, London, United Kingdom;
The Institute of Cellular Medicine, Newcastle University, Newcastle, United Kingdom
Background: Autophagy is the degradation of intracellular components by the lysosome system. Macroautophagy
is when content is sequestered in a double membrane structure which fuses with a lysosome and subsequently
the contents are degraded. Recently it has been suggested that macroautophagy plays a role in fat metabolism
within the liver. Our aim was to activate autophagocytosis in liver cells and assess the fat levels and amount of
autophagocytosis.
Methods: HUH7 cells, a liver differentiated cell line, were grown in normal or high fat medium with and
without rapamcyin, an autophagocytosis activator for 24 hours. The cells were stained with Oil Red-O (ORO)
and the percentage fat calculated using digital image analysis (DIA). Triglyceride levels within the cells were
measured biochemically as a true reflection of cell lipid content. Autophagocytosis was measured in the cells
using co-localistation of LAMP1 (a lysosomal marker) and BODIPY (a neutral lipid marker) by confocal
immunofluorescence microscopy.
Results: ORO staining identified significantly more fat in the cells grown in oleate medium compared to normal
medium (p