title: The increased transglutaminase 2 expression levels during initial tumorigenesis predict increased risk of metastasis and decreased disease-free and cancer-specific survivals in renal cell carcinoma.
abstract: OBJECTIVE
  The aim of this study was to investigate the role of transglutaminase 2(TG2) in renal cell carcinoma (RCC) by comparing the immunohistochemistry staining of primary and metastatic tumor tissues.
  
  
  METHODS
  A total of 33 metastatic RCC(mRCC) and 33 non-metastatic RCC (nmRCC) patients who were matched as closely as possible based on gender, age, nuclear grade and pathologic T stage were retrospectively investigated. TG2 immunohistochemistry staining was performed on paraffin-embedded primary tumor tissues from both patient groups and on metastatic tissues from mRCC patients. The tissues were scored from 0 to 7 according to the TG2 staining. Furthermore, the patients were stratified into two groups using median primary tumor staining score as the cutoff value: Group 1 (high risk, n = 41) and Group 2(low risk, n = 22). The clinical, histopathological and survival outcomes were compared between these risk groups using Chi-square test, t test, Mann-Whitney U test and Kaplan-Meier survival analyses.
  
  
  RESULTS
  The median TG2 score for primary tumor was 5 for the entire study population. The median primary tumor TG2 score of the mRCC patients was significantly higher compared to the nmRCC patients (6 vs. 4, p < 0.001). The TG2 score between the primary and metastatic tissues of mRCC patients was not significantly different (6 vs. 7, p = 0.086). The percentage of metastatic patients was significantly higher in Group 1 compared to Group 2 (68.3 vs. 18.2 %, p < 0.001). Kaplan-Meier analyses showed that 5-year disease-free (34.9 vs. 92.9 %, p = 0.001) and cancer-specific (47.4 vs. 86.5 %, p = 0.04) survival rates were significantly lower in high-risk group.
  
  
  CONCLUSIONS
  The increased expression of TG2 in primary tumor predicts metastasis in RCC patients and is also associated with a decrease in disease-free and cancer-specific survival outcomes.
authors.affiliation: Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Selcuk
authors.initials: S
authors.lastname: Erdem
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Gulcin
authors.initials: G
authors.lastname: Yegen
authors.affiliation: Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Turkey.
authors.forename: Dilek
authors.initials: D
authors.lastname: Telci
authors.affiliation: Department of Medical Oncology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yildiz
authors.affiliation: Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Tzevat
authors.initials: T
authors.lastname: Tefik
authors.affiliation: Department of Biostatistics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Halim
authors.initials: H
authors.lastname: Issever
authors.affiliation: Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
authors.forename: Isin
authors.initials: I
authors.lastname: Kilicaslan
authors.affiliation: Department of Urology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. sanlio@istanbul.edu.tr.
authors.forename: Oner
authors.initials: O
authors.lastname: Sanli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D063646:Carcinogenesis; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D011503:Transglutaminases / Q000096:biosynthesis* / Q000097:blood; D014421:Turkey / Q000453:epidemiology
chemical_list: D014408:Biomarkers, Tumor; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Metastasis; Renal cell carcinoma; Transglutaminase 2; Tumor marker