Winter Meeting 2011 - The Pathological Society of Great Britain ...
Winter Meeting 2011 - The Pathological Society of Great Britain ...
Winter Meeting 2011 - The Pathological Society of Great Britain ...
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P41<br />
Epithelioid Angiosarcoma Involving the Thyroid<br />
SE Low; P S Abbasi<br />
Royal Oldham Hospital, Oldham, United Kingdom<br />
BACKGROUND: Angiosarcomas usually arise in the skin and s<strong>of</strong>t tissue. Angiosarcomas<br />
involving the thyroid are rare and are aggressive tumours mostly described in people<br />
living in mountainous Alpine regions.<br />
CASE: A 73 year old man with a longstanding history <strong>of</strong> goitre presented with a mass<br />
in the left thyroid lobe. This mass extended below the suprasternal notch, displacing<br />
the trachea. Cytology showed occasional clusters <strong>of</strong> neoplastic cells with eccentrically<br />
placed nuclei within a bloodstained background. Some <strong>of</strong> these cells were binucleate,<br />
recapitulating the Reed Sternberg cells <strong>of</strong> lymphoid neoplasms. A tissue biopsy revealed a<br />
vascular tumor infiltrating the thyroid gland. <strong>The</strong> tumour was composed <strong>of</strong> large, round,<br />
epithelioid cells lining vascular spaces. Some <strong>of</strong> these cells had a plasmacytoid appearance.<br />
<strong>The</strong>se neoplastic cells were immunoreactive for CD31 and focally for AE1.AE3 but<br />
negative for thyroglobulin, TTF1 and S100.<br />
CONCLUSION: Angiosarcomas are difficult to recognize on FNA cytology especially<br />
when they occur in organs where carcinomas occur commonly (as in this case) and<br />
when cytology may simulate those <strong>of</strong> other tumours (here, a lymphoma). As they can<br />
have similar features to that <strong>of</strong> anaplastic carcinomas and can also co-express epithelial<br />
markers, an immunohistochemical panel should include vascular markers to prevent<br />
potentially erroneous diagnoses.<br />
P43<br />
B-raf Mutation and Mismatch Repair Deficiency are<br />
Significantly Correlated and Both are Commonly Found in<br />
Right-sided Stage II Colorectal Cancers.<br />
P K Southward 1 ; G Hutchins 1 ; K Handley 2 ; L Magill 2 ;<br />
C Beaumont 1 ; J Stahlschmidt 3 ; S Richman 1 ; P Chambers 1 ;<br />
M Seymour 4 ; D Kerr 5 ; R Gray 2 ; P Quirke 1<br />
1 Leeds Institute <strong>of</strong> Molecular Medicine, Leeds, United Kingdom;<br />
2 Birmingham Clinical Trials Unit, Birmingham, United Kingdom;<br />
3 Histopathology and Molecular Pathology, Leeds, United Kingdom;<br />
4 CRUK Cancer Centre, Leeds, United Kingdom; 5 Sidra Medical and<br />
Research Centre, Doha, Qatar<br />
Molecular biomarkers that could predict risk <strong>of</strong> colorectal cancer recurrence and/<br />
or sensitivity to chemotherapy would usefully complement existing histopathological<br />
prognosticators and improve patient management. B-raf mutation is associated with poor<br />
outcome in stage IV colorectal cancer whereas mismatch repair deficiency (dMMR) is a<br />
marker <strong>of</strong> good prognosis in early disease. We investigated the prognostic and predictive<br />
value <strong>of</strong> these two markers in QUASAR, a large prospective randomised trial <strong>of</strong> 5-FU/<br />
folinic acid chemotherapy versus control in stage II/III disease.<br />
B-raf codon 600 was determined by pyrosequencing and mismatch repair status by<br />
immunohistochemistry for 1354 patients. Overall 11% <strong>of</strong> tumours were dMMR and 8%<br />
B-raf mutant, consistent with previous studies.<br />
B-raf mutations occur more frequently in dMMR than MMR pr<strong>of</strong>icient tumours; 37%<br />
(58/156) compared to 5% (54/1194); pOA chondrocytes.<br />
Expression in JJ012 cells was predominantly membrane associated whilst in OA<br />
chondrocytes and C20A4 additional, predominant punctuate cytoplasmic distribution was<br />
evident. NG2/CSPG4 gene knock down was achieved in JJ012 chondrosracoma cell line<br />
with gene expression being reduced to 2.9 and 1.1 % <strong>of</strong> maximum in two constructs (B3<br />
and D1 respectively). NG2/CSPG4 protein expression was undetectable in B3 by western<br />
blotting.<br />
Discussion: Altered expression <strong>of</strong> NG2/CSPG4 in normal and transformed chondrocytes<br />
may relate to different functions. Creation <strong>of</strong> a chondrocyte cell line that has stable<br />
knock down <strong>of</strong> NG2/CSPG4 will allow further investigation <strong>of</strong> NG2/CSPG function in<br />
chondrocytes.<br />
P44<br />
Expression <strong>of</strong> the Phosphorylated ERK and MEK MAPKs<br />
and Upstream Growth Factor Receptors in Adenomas and<br />
Carcinomas <strong>of</strong> Patients with Familial Adenomatous Polyposis<br />
P JRF Hollingshead 1 ; J Wang 2 ; N El-Masry 3 ; P Trivedi 4 ;<br />
D Horncastle 2 ; I Talbot 5 ; MR Alison 6 ; I Tomlinson 7 ;<br />
M El-Bahrawy 2<br />
1 Department <strong>of</strong> Surgery, Chelsea and Westminster Hospital, United<br />
Kingdom; 2 Department <strong>of</strong> Histopathology, Imperial College, Hammersmith<br />
Hospital, United Kingdom; 3 Department <strong>of</strong> Surgery, Charing Cross<br />
Hospital, United Kingdom; 4 Department <strong>of</strong> Histopathology, Hammersmith<br />
Hospital, United Kingdom; 5 St Mark’s Hospital, London, United Kingdom;<br />
6 Queen Mary University, London, United Kingdom; 7 Cancer Research UK,<br />
Oxford, United Kingdom<br />
Familial Adenomatous Polyposis (FAP) is an autosomal dominant condition characterised<br />
by the development <strong>of</strong> multiple colonic adenomas with likely progression <strong>of</strong> some<br />
to invasive cancer. <strong>The</strong> ERK MAPK pathway is a signalling pathway activated by the<br />
Epidermal Growth Factor Receptor-1 (EGFR). <strong>The</strong> aim <strong>of</strong> this study is to investigate the<br />
expression <strong>of</strong> key members <strong>of</strong> this pathway in colonic tumours <strong>of</strong> FAP patients. Fifteen<br />
patients with FAP who had developed colorectal cancer were identified and colectomy<br />
specimens reviewed. We studied the expression <strong>of</strong> EGFR, HER2, phosphorylated ERK<br />
(pERK) and phosphorylated MEK (pMEK) by immunohistochemistry on formalin fixed<br />
paraffin embedded tissue from normal tissue, multiple adenomas, and carcinomas from<br />
each patient. <strong>The</strong>re was a statistically significant increase in nuclear staining intensity for<br />
pERK in adenomas (p=0.0017) and carcinomas (p=0.0067) compared to normal tissue.<br />
<strong>The</strong>re was a statistically significant increase in nuclear staining intensity for pMEK in<br />
carcionomas compared to normal tissue (p=0.001). EGFR expression correlated with<br />
pERK nuclear staining (p=0.0015) but not with pMEK nuclear staining. HER2 staining<br />
was weak in all tumours examined, and no significant correlations were found between<br />
HER2 expression and other markers. <strong>The</strong>se data suggest a progressive increase in activity<br />
in the ERK MAPK pathway from normal tissue through adenoma to carcinoma in FAP<br />
tumours, which correlates with EGFR, but not with HER-2 expression. <strong>The</strong> activation <strong>of</strong><br />
this pathway appears to be an early event in the pathogenesis <strong>of</strong> these tumours, suggesting<br />
members <strong>of</strong> this pathway can be therapeutic targets for control <strong>of</strong> development and<br />
progression <strong>of</strong> colonic tumours in FAP patients.<br />
32 Visit our website: www.pathsoc.org | <strong>Winter</strong> <strong>Meeting</strong> (199 th ) 6 – 7 January <strong>2011</strong> | Scientific Programme