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

Abstract

To investigate the clinical characteristics, treatments and prognosis of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2 tRCC), the epidemiological features and treatment results of 34 cases of Xp11.2 tRCC, which were diagnosed by immunohistochemistry staining of TFE3 and fluorescence in situ hybridization at our center, were retrospectively reviewed. The 34 patients included 21 females and 13 males aged 3 to 64 years (median age: 27 years). Four patients were children or adolescents (<18 years of age), and 26 patients were young or middle-aged adults (18–45 years). Radical nephrectomy was performed on 25 patients. Laparoscopic nephron-sparing surgery was performed on 9 patients who presented with an isolated mass with a small diameter (<7 cm) and well-defined boundary on computed tomography imaging. Postoperative staging showed that 25 cases (73.53%) were at stage I/II, while 9 cases (26.47%) were at stage III/IV. All stage I/II patients received a favorable prognosis with a three-year overall survival rate of 100%, including the patients who underwent laparoscopic nephron-sparing surgery. With the exception of 2 children, the other 7 stage III/IV patients died or developed recurrence with a median follow-up of 29 months. On univariate analysis, maximum diameter, adjuvant treatment, TNM stage, lymph node metastasis, inferior vena cava tumor thrombosis and tumor boundary were identified as statistically significant factors impacting survival (P<0.05). Multivariate analysis indicated that TNM stage and inferior vena cava tumor thrombosis were independent prognostic factors (P<0.05). In conclusion, Xp11.2 tRCC is a rare subtype of renal cell carcinoma that mainly occurs in young females. Nephron-sparing surgery was confirmed effective preliminarily in the treatment of small Xp11.2 tRCCs with clear rims. Advanced TNM stage and inferior vena cava tumor thrombosis were associated with poor prognosis.

Preoperative Plasma Fibrinogen: An Independent Predictor for Survival in Adult Patients with Xp11.2 Translocation Renal Cell Carcinoma

“…Although a prior meta-analysis suggested a female gender predominance in adult XP11.2 translocation RCC [13] , possibly due to its X-chromosome related nature, our study found an equal gender distribution as observed in children which might be explained by the absence of translocation on the Barr body (inactive X chromosome) or by the relatively small number of patients enrolled. Moreover, consistent with previous reports [7,18] and for unknown reasons, right side prevalence was observed in our cohort.…”

“…In regard to the risk of disease reoccurrence and death, it is important to conduct prognostic studies to identify potential preoperative risk factors for disease progression and death which might help to guide interventions in the future. Moreover, prognostic researches for adult patients, should be especially encouraged due to at least three reasons: rstly, as a rare disease which mainly affects children [4] , data for adult patients is scarce for the time being which awaits further illumination; secondly, this disease manifests with a more aggressive behavior in adults than in children [3] which suggests a possibly different prognostic features in adults; thirdly, prior prognostic studies, which revealed several possible risk factors as neutrophil-to-lymphocyte ratio (NLR), C-reactive protein/albumin ratio (CRP/Alb ratio), platelet-to-lymphocyte ratio (PLR), tumor stage and inferior vena cava tumor thrombosis, included both child and adult patients [6,7] for analysis which might bring bias. Therefore, it would be of importance to identify novel prognostic factors in adult XP11.2 translocation RCC patients.…”

Renal cell carcinoma associated with Xp11 translocation involving the gene

“…Результаты FISH-реакции позволили выявить нарушения в области короткого плеча Х-хромосомы (Хр11.2), ассоциированной с транслокацией гена TFE3 (рис. 10) [5]. Ген TFE3 кодирует транскрипционный фактор с основным доменом типа спираль-петля-спираль (Basis-helixloop-helix -bHLH), который связан с IGHM энхансером 3.…”

Clinical efficacy of cabozantinib in two pediatric patients with recurrent renal cell carcinoma

“…RCC in children has higher rates of lymph node and distant metastases than in adults, and up to half of children suffer recurrence after primary surgical resection . Patients with localized tumors at diagnosis have >90% survival after resection, but <15% of patients with Stage 4 disease will survive . The use of adjuvant molecularly targeted therapies, as per NCCN guidelines, is associated with toxicity in adults without durable benefit.…”

“…6 Patients with localized tumors at diagnosis have >90% survival after resection, but <15% of patients with Stage 4 disease will survive. 7 The use of adjuvant molecularly targeted therapies, as per NCCN guidelines, 8 is associated with toxicity in adults 9 without durable benefit. Additional therapies are FDA approved for relapsed RCC, but most have limited benefit in adults with median event-free survival of less than 1 year.…”