Martine De Herdt

44 Chapter 3 Ethics statement Human tissues and patient data were used according to “The Code for Proper Secondary Use of Human Tissue” and “The Code of Conduct for the Use of Data in Health Research” as stated by the Federation of Dutch Medical Scientific Societies (Federa FMVV, updated 2011). Patient material Patients with histologically confirmed oral or oropharyngeal SCC – whose primary treatment was surgery – were included in this study. Patients diagnosed with synchronous primary cancers or previous malignancies in the head and neck region were excluded. Human papillomavirus type 16 (HPV-16) status was determined for all oropharyngeal SCC by means of the algorithm described by Smeets et al. (34) using the methods described by van Kempen et al. (35). With the exception of the peptide length and amino acid mapping regions for CVD13, C-12 and C-28, the information summarized in the table above is extracted from the datasheets provided with the antibodies. The detailed information concerning the peptide length and/or amino acid mapping regions for CVD13, C-12 and C-28, is obtained through direct communication (telephone and e-mail) with the technical support services of Invitrogen™ (CVD13) and Santa Cruz Biotechnology, Inc. (C-12 and C-28). To examine MET immunohistochemical reactivity in routinely processed FFPE primary oral SCC, representative tissue blocks of four cancers were randomly collected from the archives of the department of pathology of the Leiden University Medical Center (LUMC, The Netherlands). To investigate the association between MET immunohistochemical reactivity and survival, a tissue microarray (TMA) representing 240 FFPE primary oral or oropharyngeal SCC – surgically removed between 1996 and 2005 in the University Medical Center Utrecht (UMCU, the Netherlands) – was included in the study. Prior to the TMA’s construction, hematoxylin and eosin (HE) sections – representing the selected cancers – and their corresponding FFPE tissue blocks were collected from the tissue archive of the department of pathology of the UMCU. Subsequently, a dedicated head and neck pathologist examined all HE slides with special attention to the following pathological characteristics: cancer type, differentiation grade, infiltration depth, growth pattern, perineural invasion, vasoinvasive growth, extranodal growth and bone invasion and selected vital cancer regions that were properly fixated for

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