94 CHAPTER 4 RESULTS CLINICOPATHOLOGICAL CHARACTERISTICS Twenty-six patients with mRCC were identified who underwent resection of a primary tumor (n=23) or metastatic lesion (n=3) and received sunitinib as first-line palliative therapy upon progression or relapse (Table 1, Supplementary Table 1). The median time between surgery and start of sunitinib was six months (range 1-63). Eighteen patients were sensitive to sunitinib, of whom six had an objective response. The median PFS (mPFS) in this group was 8.8 months (range 5 – 62.3). Eight patients had progressive disease as best response (mPFS 2.3 months, range 1.5 – 2.8). Table 1. Patient characteristics 1 Consists of more than one histological type: clear cell + papillary, clear cell + sarcomatoid, clear cell + eosinophilic variant. Time to sunitinib indicates interval between resection and initiation of sunitinib treatment; PFS, progression-free survival. All patients (n = 26) Sensitive (n = 18) Primary resistant (n = 8) Age (years), median (range) 60 (20-80) 61 (40-79) 58 (20-80) Sex, n (%) Female 11 (42) 8 (44) 3 (38) Male 15 (58) 10 (56) 5 (62) Histology, n (%) Clear cell carcinoma 17 (65) 13 (72) 4 (50) Papillary carcinoma 3 (12) 1 (6) 2 (25) Mixed type1 6 (23) 4 (22) 2 (25) Prior systemic therapy, n (%) 0 17 (65) 10 (55) 7 (88) 1 8 (31) 7 (39) 1 (12) 2 1 (4) 1 (6) - PFS (months), median (range) 8.8 (5-62.3) 2.3 (1.5-2.8) Time to sunitinib (months), median (range) 6 (1-63) 6 (1-63) 6 (1-24) TYROSINE-PHOSPHOPROTEOMICS ANALYSIS Twenty-three out of 26 tumor tissues (16 sensitive and seven primary resistant patients) were evaluable for tyrosine-phosphoproteomics, with a median protein input of 5 mg (range 2-5 mg) per sample. Three samples were considered not evaluable; two had a very low phosphopeptide yield and one had a low protein yield, hindering lysate-based normalization. In total, 2656 unique class 1 phosphosites were identified in tumor and control samples. After eliminating all control sample-specific sites, 1596 unique class 1 phosphosites remained for further comparative analysis between the two groups (86% tyrosine, 9% serine and 5% threonine, showing adequate enrichment for tyrosine phosphorylated peptides), with a median of 415 (range 266
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