Clinicopathological characteristics of Xp11.2 translocation renal cell carcinoma in adolescents and adults: Diagnosis using immunostaining of transcription factor E3 and fluorescence in situ hybridization analysis

Abstract

Objectives: To determine the rate and clinicopathological features of Xp11.2 translocation carcinoma using immunostaining of transcription factor E3 and fluorescence in situ hybridization analysis. Methods: We evaluated 638 patients with renal cell carcinoma treated at Sapporo Medical University Hospital, Sapporo, Japan, from 1990 to 2009 by reviewing all hematoxylin-eosin-stained sections and carrying out immunostaining of transcription factor E3 for all cases. Fluorescence in situ hybridization analysis was carried out for patients with positive immunostaining or with findings suspicious for Xp11.2 translocation carcinoma on hematoxylin-eosin-stained sections. In this analysis, we set a cut-off level for split signals of at least 10% of nuclei. Results: Of the 631 patients, 20 (3.2%) were positive for immunostaining. Finally, five patients were diagnosed with Xp11.2 translocation carcinoma (0.8%). Four of these patients were female and aged less than 50 years, and three cases were diagnosed as stage IV with multiple regional lymph nodal or visceral metastases. The positive predictive value of immunostaining was 25%. Conclusion: Patients with Xp11 translocation renal cell carcinoma tend to be younger, more frequently female and diagnosed at a more advanced stage. Immunostaining followed by fluorescence in situ hybridization analysis is an accurate and cost-effective approach for diagnosis of Xp11 translocation renal cell carcinoma.

Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusions: Clinical Features, Treatments and Prognosis

“…In the current study, a predominance of young females and right side prevalence was observed, which is consistent with previous reports [4, 22, 24]. In the report by Argani on 28 cases of Xp11.2 tRCC, there was a strong female (22 cases, 79%) and a slight right (14/22, 64%) preference, of which 22 cases (79%) were younger than 45 years [22].…”

“…Xp11.2 tRCC typically affects children and young adults under 45 years of age [3, 4, 19, 20] with a one-third incidence in juveniles and 0.2–5.0% incidence in adults [16, 21–23]. Unlike pediatric RCCs, cytogenetics is not routinely performed for adult RCCs due to the relatively lower incidence rate, which results in most misdiagnoses as conventional RCCs.…”

“…Thus, TFE3-IHC can be performed proactively as a screening test, and FISH can be performed as a verification test. Hirobe and Masumori suggested that the combination of TFE3-IHC and FISH is an effective method to diagnose Xp11.2 tRCCs, which can improve specificity and potentially eliminate false-positives resulting from overstaining [4]. …”

“…Microscopically, Xp11.2 tRCC is similar to clear cell renal cell carcinoma (CCRCC) or papillary renal cell carcinoma (PRCC) [4, 8], which makes it difficult for pathologists to distinguish Xp11.2 tRCC from other tumor types by histological characteristics. Although immunohistochemical staining for TFE3 (TFE3-IHC) serves as the basic method for the diagnosis of Xp11.2 tRCC, numerous reports have shown that TFE3-IHC has fairly high false-positive rates and low predictive values, which results in misdiagnoses in patients [4, 9–11].…”

“…Although immunohistochemical staining for TFE3 (TFE3-IHC) serves as the basic method for the diagnosis of Xp11.2 tRCC, numerous reports have shown that TFE3-IHC has fairly high false-positive rates and low predictive values, which results in misdiagnoses in patients [4, 9–11]. To date, TFE3 break-apart fluorescence in situ hybridization (FISH) is regarded as the best method to diagnose Xp11.2 tRCC due to its advantages of high sensitivity and specificity [2, 12–15].…”