No abstract

Background: A Disintegrin And Metalloprotease (ADAM) 9 has been implicated in tumour progression of various solid tumours, however, little is known about its role in renal cell carcinoma. We evaluated the expression of ADAM9 on protein and transcript level in a clinico-pathologically characterized renal cell cancer cohort.Methods: 108 renal cancer cases were immunostained for ADAM9 on a tissue-micro-array. For 30 additional cases, ADAM9 mRNA of microdissected tumour and normal tissue was analyzed via quantitative RT-PCR. SPSS 14.0 was used to apply crosstables (Fisher's exact test and χ 2 -test), correlations and univariate as well as multivariate survival analyses.Results: ADAM9 was significantly up-regulated in renal cancer in comparison to the adjacent normal tissue on mRNA level. On protein level, ADAM9 was significantly associated with higher tumour grade, positive nodal status and distant metastasis. Furthermore, ADAM9 protein expression was significantly associated with shortened patient survival in the univariate analysis. Conclusion:ADAM9 is strongly expressed in a large proportion of renal cell cancers, concordant with findings in other tumour entities. Additionally, ADAM9 expression is significantly associated with markers of unfavourable prognosis. Whether the demonstrated prognostic value of ADAM9 is independent from other tumour parameters will have to be verified in larger study cohorts.

Background: The three far-upstream element (FUSE) binding proteins (FBP1, FBP2, and FBP3) belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear.

Purpose: Claudin-1is a tight junction protein described in normal tissues as well as in malignancies. We aimed to assess the diagnostic or prognostic significance of claudin-1 expression in renal cell carcinoma and to correlate the expression of claudin-1 with clinical, histopathologic, and prognostic parameters in renal cell carcinoma. Experimental Design: A tissue microarray was constructed using formalin-fixed, paraffinembedded tissue from renal cell carcinomas and corresponding normal renal tissue from 318 patients.The protein expression of claudin-1was assessed and correlated to clinicopathologic tumor parameters including patient survival. A separate cohort of 44 papillary renal cell carcinoma was used for validation of results. Results: Claudin-1was expressed in 29.9% of renal cell cancer cases.Whereas the vast majority of clear cell carcinomas were negative for claudin-1, most papillary tumors (76-86%) were positive. Claudin-1expression was associated with markers of unfavorable tumor biology in clear cell renal cell carcinoma, whereas the opposite was valid for papillary renal cell carcinoma. In clear cell renal cell carcinoma claudin-1 positivity was a prognosticator of shortened disease-specific patient survival in univariate analysis (P = 0.008), which also remained significant in multivariate analyses in the clinically important subgroups of nonmetastasized or asymptomatic patients. Conclusions: Claudin-1is expressed in the majority of papillary renal cell carcinomas, suggesting a diagnostic value of this marker. Its expression is an independent prognosticator of shortened disease-specific patient survival in clinically relevant subgroups of clear cell renal cell carcinoma. Further functional studies are needed to clarify the different biological roles of claudin-1 expression in these histologic subtypes of renal cell carcinoma.

Aims: Determining the origin of metastases is an important task of pathologists to allow for the initiation of a tumor-specific therapy. Recently, homeobox protein Hox-B13 (HOXB13) has been suggested as a new marker for the detection of prostatic origin. The aim of this study was to evaluate the diagnostic sensitivity of HOXB13 in comparison to commonly used immunohistochemical markers for prostate cancer. Materials and methods: Histologically confirmed prostate cancer lymph node metastases from 64 cases were used to test the diagnostic value of immunohistochemical markers: prostate specific antigen (PSA), Prostatic acid phosphatase (PSAP), prostate specific membrane antigen (PSMA), homeobox gene NKX3.1, prostein, androgen receptor (AR), HOXB13, and ETS-related gene (ERG). All markers were evaluated semi-quantitatively using Remmele’s immune reactive score. Results: The detection rate of prostate origin of metastasis for single markers was 100% for NKX3.1, 98.1% for AR, 84.3% for PSMA, 80.8% for PSA, 66% for PSAP, 60.4% for HOXB13, 59.6% for prostein, and 50.0% for ERG. Conclusions: Our data suggest that HOXB13 on its own lacks sensitivity for the detection of prostatic origin. Therefore, this marker should be only used in conjunction with other markers, preferably the highly specific PSA. The combination of PSA with NKX3.1 shows a higher sensitivity and thus appears preferable in this setting.