CUPPRINT TM. Managing Cancer is difficult enough Diagnosing shouldn t be 82% Gene expression profiling to classify Cancer of Unknown Primary

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1 82% accuracy Managing Cancer is difficult enough Diagnosing shouldn t be Gene expression profiling to classify Cancer of Unknown Primary CUPPRINT TM AGENDIA UNVEILING TUMOR ORIGIN

2 CUPPRINT TM Gene expression will tell you the origin 39 tumor types adrenal brain breast carcinoid-intestine cervix-adeno cervix-squamous endometrium gallbladder germ-cell-ovary gist kidney leiomyosarcoma liver lung-adeno-large-cell lung-small lung-squamous lymphoma-b lymphoma-hodgkins lymphoma-t meningioma mesothelioma osteosarcoma ovary-clear ovary-serous pancreas prostate skin-basal-cell skin-melanoma skin-squamous small-and-large-bowel soft-tissue-liposarcoma soft-tissue-mfh soft-tissue-sarcoma-synovial stomach-adeno testis-other testis-seminoma thyroid-follicular-papillary thyroid-medullary urinarybladder CupPrint TM report CUPPRINT TM ANALYSIS RESULT Using the compiled database of 591 cancer cases, a statistical method was develped for the discrimination of 39 different tumor types. The five closest Nearest Neighbours in the database to the tissue sample you sent in are reported. Breast Breast Breast Breast Breast Interpretation CupPrint: indicates primary tumor type as breast cancer CupPrint test result explained in this section of the report.

3 Diagnosis The diagnosis "Cancer of Unknown Primary" (CUP) refers to a tumor with no identifiable primary site. It constitutes a significant health problem, as the site of origin of any cancer holds important clues to the optimal therapeutic intervention. The identification of the correct site of origin is crucial therefore to the optimal management of CUP. Modern pathology and imaging procedures lead to successful identification of the site of origin in only some 25% of all cases of CUP, even after the most thorough diagnostic work-up. In summary, CUP constitutes a diagnostic dilemma and a therapeutic challenge. The uncertain origin of the tumor causes anxiety among not only the patients and their families, but also physicians. Why CupPrint TM Unknown primary carcinomas are a significant health problem, constituting 3% to 5% of all tumors diagnosed Source: Average percentage of incidence given in published data Clinical data supports the belief that patients who have CUP that are later proved to have originated from a given site or from unique histology have an overall prognosis similar to that of patients who present with a known primary tumor 1) 1) unknown primary carcinoma:diagnosis and management, JPM Ayoub, KP Hubbard, R Lenzi. 1995, % Accuracy for the top 34 tumor types in the CUP database 2) 2) MG Erlander et al, ASCO 2004 [poster] Evaluation of patients presenting with CUP is expensive. One study reported the average costs of investigations to be $ ) Although only a minority of patients will have curable disease or a disease for which there is substantial palliative benefit, the appropriate use of special diagnostic pathology and selected radiology studies will identify patients for whom directed therapy will provide the best possible chance for response 3) 3)

4 CUPPRINT TM Gene expression will give you the answer Illustration: Arthur Rep CupPrint TM shows an overall diagnostic accuracy of 82% CupPrint TM utilises standard FFPE samples (formalin fixed paraffin embedded) CupPrint TM is a simple and time saving diagnostic test procedure (centralised service) CupPrint TM meets the highest international diagnostic laboratory standards CupPrint TM supports clinical treatment decision and patient management

5 How to order CUPPRINT TM A step by step guide and fax form service 1. Sign up for a customer account Online Visit Agendia s website at Select the customer pages option in top menu and click the link to enter the customer pages. Select sign-up for account and follow instructions on screen. By fax Fill out contact details below and fax this form to By Send an with the contact details to By telephone Contact Agendia on and request a customer account. Contact details: Name: Hospital: Department: Street: Town: Postal Code: County/State: Country: Telephone: Fax: You will receive account information within 2 working days. You will receive f.o.c. CupPrint TM service packs for diagnostic procedures. Step by step instructions provided in service pack. 2. Ordering tests / shipping samples Online Visit Agendia s customer pages and sign into your personal account. Select submit sample and follow instructions on screen. Other Contact Agendia on for alternative method. When sending in samples, service packs will be replenished automatically. Easy tracking of samples online through your personal account. Real time review of end results online. Patient PDF report available online and automatically provided by AGENDIA FAX NUMBER

6 Send to Agendia. CupPrint TM service pack Put slid er back in envelope. Remove slid er from sampling kit. Take out glass slides provided. " Place glass slides in slid er. Stretch paraffin sections on clean waterbath. Pick sections onto glass slide. Slotervaart Medical Center, 9D, Louwesweg 6, NL-1066 EC Amsterdam The Netherlands Phone: Fax: CP-GB /v1.0 All rights reserved.cupprint and Agendia are registered trademarks of Agendia BV, Amsterdam. The Netherlands For more detailed information please visit our website: