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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

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