XPA-210: a new proliferation marker determines locally advanced prostate cancer and is a predictor of biochemical recurrence.

PURPOSE: XPA-210 is a proliferation marker derived from Thymidine kinase-1. It is of clinical significance in kidney, breast, and bladder cancer. There are no data available for XPA-210 in prostate cancer (PC). Herein, we aim to determine the clinical usefulness of XPA-210 in PC. MATERIALS AND METHODS: In a retrospective study, cancer and benign tissue samples of 103 patients (median age 65 years, median PSA 9.04 ng/ml, median Gleason score 6) who underwent prostatectomy were constructed to a tissue micro array and stained for XPA-210. Semi-quantitative results were correlated with pathological and clinical data by Wilcoxon-Kruskall-Wallis and linear regression analysis. Expression levels in PC were correlated between the time of biochemical recurrence and the time to development of metastasis by the Kaplan-Meier method. Multivariate analysis was done to correlate those with the resection status. RESULTS: Mean staining score was 0.51-0.14 for tumor and benign tissue (P < 0.0001). Tumor staining score was significantly associated with Gleason score <6/≥6 (P < 0.0001) and T2/T >2 (P = 0.0007). When dividing the tumor score by the mean value, higher expression of XPA-210 was associated with a shorter time to biochemical recurrence (P = 0.003) and time to development of metastasis (P = 0.0061). Tumor staining (P = 0.0371) was an independent prognostic factor for biochemical relapse regardless of resection status. CONCLUSIONS: XPA-210 is a new tissue-based prognostic marker for prostate cancer histopathology. It reliably differentiates tumor and normal prostatic tissue predicting biochemical relapse and onset of metastatic disease. XPA-210 might be clinically useful for individual decision-making in PC-treatment.

Exposed proliferation antigen 210 (XPA-210) in renal cell carcinoma (RCC) and oncocytoma: clinical utility and biological implications.

OBJECTIVE: • To determine the clinical role of the exposed proliferation antigen 210 (XPA-210) of the proliferation marker thymidine kinase 1 (TK1) in a large cohort of different renal cell carcinoma (RCC) types, oncocytomas and normal renal tissues samples, as TK1 is reported to be of clinical significance in several cancer entities and is suggested as a prognostic serum biomarker for RCC. PATIENTS AND METHODS: • Expressions of XPA-210 were determined immunohistochemically in 40 clear cell RCCs (ccRCC), 25 papillary RCCs (papRCC), 17 chromophobe RCC (chRCC), 27 oncocytomas and 64 normal renal parenchyma paraffin-embedded specimens. • Immunohistochemistry was performed with a monoclonal anti-XPA-210 antibody. Staining was measured by the percentage of positive cells. • Expression was compared between subgroups and correlated with respective clinical data using one-way analysis of variance with post hoc Tukey-Kramer analyses. RESULTS: • XPA-210 staining in the RCC subgroup was significantly different from the oncocytomas (mean [sem] 4.1 [0.4] vs 2.2 [0.4]; P = 0.004) and from normal renal tissue (1.0 [0.1]; P < 0.001], whereas oncocytomas did not differ from normal renal parenchyma staining (P = 0.18). • Subdivided into RCC groups, only ccRCC (mean [sem] 5.1 [0.6]; P < 0.001) and papRCC (4.4 [0.6]; P < 0.001) varied from normal renal parenchyma, whereas chRCC (1.4 [0.3]; P = 0.99) did not. • RCC XPA-210 staining was significantly associated with higher tumour stage (T = 3, P = 0.002) and grade (G = 3, P = 0.001). CONCLUSIONS: • The malignant character of RCC is reflected by higher XPA-210 expression as compared with oncocytomas and normal kidney. • The ccRCC and papRCC subgroups had higher XPA-210 levels. • XPA-210 could be considered a potential marker for the assessment of the proliferative activity in primary RCC.

XPA-210: a new proliferation marker to characterize tumor biology and progression of renal cell carcinoma.

PURPOSE: Recent lung cancer data have shown an association of XPA-210, a key peptide of thymidine kinase, with advanced disease. We thus assessed its proliferation status in primary (M0) and metastatic (M1) renal cell carcinoma (RCC). METHODS: Paraffin slides from 30 patients (mean age: 61.2 years; range: 42-84) with clear-cell RCC (M0 in 10; non-osseous M1 in 10; osseous M1 in 10) were T-matched for pT1/pT3. Corresponding malignant and benign renal parenchyma were immunohistochemically stained against XPA-210. Staining density was determined by a semi-quantitative score of positive cell shares. Staining intensity included the precise cellular location. RESULTS: XPA-210 occurred predominantly in the nucleus, with a minor cytoplasmatic component. RCC tissue showed higher density and stronger intensity than did benign renal tissue in both nucleus (P = 0.005) and cytoplasm (P = 0.01). Density and intensity were positively associated with tumor diameters ≤7 cm, whereas they tended to correlate inversely in tumors >7 cm (P 0.07). Density of stained cells was significantly higher in metastatic than in localized RCC in both nucleus and cytoplasm (P < 0.04). Non-osseous M1 tissue showed significantly higher nuclear and cytoplasmatic expression than did M0 tissue (P < 0.05), whereas osseous M1 tissue did not. CONCLUSIONS: In all RCC tissues, XPA-210 staining was significantly higher in the nucleus than in cytoplasm, potentially owing to large cytoplasmatic spaces as a characteristic histologic feature of clear-cell component. XPA-210 expression gradually increased from localized to metastatic disease, peaking in patients without bone involvement. Therefore, XPA-210 might aid the selection of appropriate adjuvant treatment in high-risk patients.