Identification of Ser-1275 and Ser-1309 as autophosphorylation sites of the insulin receptor 1This paper is dedicated to Prof. Günter Legler on the occasion of his 70th birthday.1

AbstractWe have identified Ser-1275 and Ser-1309 as novel serine autophosphorylation sites by direct sequencing of HPLC-purified tryptic phosphopeptides of the histidine-tagged insulin receptor kinase IRKD-HIS. The corresponding peptides (Ser-1275, amino acids 1272–1292; Ser-1309, amino acids 1305–1313) have been detected in the HPLC profiles of both the soluble kinase IRKD, which contains the entire cytoplasmic domain of the insulin receptor β-subunit, and the insulin receptor purified from human placenta. In contrast, a kinase negative mutant, IRKD-K1018A, did not undergo phosphorylation at either the tyrosine or serine residues, strongly suggesting that insulin receptor kinase has an intrinsic activity to autophosphorylate serine residues

Increased ERCC1 expression is linked to chromosomal aberrations and adverse tumor biology in prostate cancer

Abstract Background Animal model experiments have suggested a role of the DNA repair protein ERCC1 (Excision Repair Cross-Complementation Group 1) in prostate cancer progression. Methods To better understand the impact of ERCC1 protein expression in human prostate cancer, a preexisting tissue microarray (TMA) containing more than 12,000 prostate cancer specimens was analyzed by immunohistochemistry and data were compared with tumor phenotype, PSA recurrence and several of the most common genomic alterations (TMPRSS2:ERG fusions: deletions of PTEN, 6q, 5q, 3p). Results ERCC1 staining was seen in 64.7% of 10,436 interpretable tissues and was considered weak in 37.1%, moderate in 22.6% and strong in 5% of tumors. High-level ERCC1 staining was linked to advanced pT stage, high Gleason grade, positive lymph nodes, high pre-operative serum PSA, and positive surgical margin status (p < 0.0001 each). High ERCC1 expression was strongly associated with an elevated risk of PSA recurrence (p < 0.0001). This was independent of established prognostic features. A subgroup analysis of cancers defined by comparable quantitative Gleason grades revealed that the prognostic impact was mostly driven by low-grade tumors with a Gleason 3 + 3 or 3 + 4 (Gleason 4: ≤5%). High ERCC1 expression was strongly associated with the presence of genomic alterations and expression levels increased with the number of deletions present in the tumor. These latter data suggest a functional relationship of ERCC1 expression with genomic instability. Conclusion The results of our study demonstrate that expression of ERCC1 - a potential surrogate for genomic instability - is an independent prognostic marker in prostate cancer with particular importance in low-grade tumors

Additional file 3: of Self-administered version of the Fabry-associated pain questionnaire for adult patients

Not yet validated English translation of the self-administered Fabry Pain Questionnaire. (DOC 275 kb

Increased lysophosphatidylcholine acyltransferase 1 expression is unrelated to prognosis of esophageal cancer patients

Introduction!#!Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has repeatedly been suggested to be associated with tumorigenesis. To evaluate the role of LPCAT1 in esophageal cancer, LPCAT1 immunostaining was analyzed on a tissue microarray containing samples from esophageal cancer patients.!##!Results!#!In benign esophageal tissue, LPCAT1 staining was detectable in low intensities. LPCAT1 staining was increased in malignant as compared to benign esophageal tissue and was found in high intensity in 26.4% of 288 interpretable esophageal adenocarcinomas (EACs) and in 23.2% of 211 squamous cell carcinomas (ESCCs). Increased LPCAT1 staining was linked to undifferentiated tumor grading in both subtypes of EACs and ESCCs (p = 0.0273 and p = 0.0085).!##!Conclusion!#!However, LPCAT1 was not associated with prognosis of EAC and ESCC patients (p = 0.6838 and p = 0.4695) and thus cannot be considered a prognostic biomarker in esophageal cancers

Additional file 1: of Self-administered version of the Fabry-associated pain questionnaire for adult patients

Supplementary methods. (DOC 40 kb

Y-chromosome loss is frequent in male renal tumors

Background: Loss of the Y-chromosome is a common event in different tumor types but its prevalence and clinical relevance in renal cell tumors is still not understood. Methods: It was the aim of this study to estimate the frequency and clinical relevance of Y-loss in kidney neoplasms. A cohort of 1,252 male renal tumors was analyzed in a tissue microarray format by fluorescence in-situ hybridization (FISH). Results: Y-loss was found in 47% of tumors. The frequency of this alteration varied markedly between kidney tumor subtypes. Y-loss was most prevalent in papillary renal cell carcinoma (RCC) (77%) followed by chromophobe RCC (60%), oncocytoma (51%), clear cell RCC (39%) and clear cell (tubulo)papillary RCC (19%). Y-loss was linked to higher patient age and smaller tumor size at diagnosis. Mean age (95% CI) was 65 (64-66) years in patients with Y-loss in their tumor compared to 60 (58-61) years in patients without Y-loss (P<0.0001). Significant correlations between Y-loss and tumor phenotype were found only for papillary carcinomas (P=0.002), especially for type 1 (P=0.03). Conclusions: Y-loss is present in different histologic subtypes of renal neoplasm. The highest frequency is in papillary RCC, where it may represent a potentially relevant prognostic biomarker suggesting favorable disease outcome

p53 overexpression is a prognosticator of poor outcome in esophageal cancer

Immunohistochemistry studies on p53 inactivation in esophageal cancer are available with inconclusive results. Data on the combined effect of p53 protein accumulation and TP53 genomic deactivation in large scale studies for esophageal cancer are currently lacking. A tissue microarray with 691 esophageal cancer samples was analyzed by p53 immunohistochemistry and fluorescence in situ hybridization (FISH). Nuclear p53 accumulation was observed in 45.9% of patients with adenocarcinoma (AC) and in 40.0% in squamous cell carcinoma (SCC). Heterozygous TP53 deletions occurred in 40.9% in AC and in 19.4% in SCC. Homozygous deletions did not occur at all. High-level p53 immunostaining was associated with shortened overall survival in AC and SCC while TP53 deletions alone showed no correlation with survival. High-level p53 immunostaining in patients with AC was associated with advanced tumor (P=0.019) and Union for International Cancer Control stages (P=0.004), grading (P=0.027) and the resection margin status (P=0.006). Associations between p53 immunostaining and SCC were not found. TP53 deletions were found to be associated with advanced tumor stages (P=0.028) and the presence of lymph node metastasis (P=0.009) in SCC. In conclusion, strong p53 immunostaining, but not TP53 deletion alone, is associated with unfavorable outcomes and may therefore represent a clinically useful molecular marker in esophageal cancer