ALK alterations in adult renal cell carcinoma: frequency, clinicopathologic features and outcome in a large series of consecutively treated patients

Molecular cytogenetic analysis for TFE3 rearrangement in Xp11.2 renal cell carcinoma and alveolar soft part sarcoma: validation and clinical experience with 75 cases

“…Of importance, significantly worse cancer-specific survival was found for Xp11.2 papillary-type renal cell carcinoma compared with TFE3 negative papillary renal cell carcinoma. 8 This result is consistent with other literature suggesting Xp11.2 renal cell carcinoma has a relatively more aggressive clinical course in adults. 3,[9][10][11][12][13][14] For example, in one of the largest reports to date, half of the 28 adults (Z20 years of age at diagnosis) with Xp11.2 renal cell carcinoma presented at stage IV and 85% of cases in which lymph nodes were resected were positive for metastasis.…”

“…8 Two of the abnormal TFE3 breakapart probe results had a 2R2G pattern in males, suggesting rearrangement of two TFE3 copies, which was not a pattern seen during the probe validation or subsequent clinical experience. Of importance, significantly worse cancer-specific survival was found for Xp11.2 papillary-type renal cell carcinoma compared with TFE3 negative papillary renal cell carcinoma.…”

“…3,7 In contrast, adults are now known to be affected, and evidence is accumulating that TFE3 rearrangement in adult renal cell carcinoma may have a more aggressive course. [8][9][10][11][12][13][14] The TFE3 gene (transcription factor for immunoglobulin heavy-chain enhancer 3) at Xp11.2 is a member of the microphthalmia-associated (MITF) family of basic helix-loop-helix leucine zipper transcription factors. 15 TFE3 can fuse to multiple partners in Xp11.2 renal cell carcinoma; most commonly ASPSCR1 (also called ASPL) resulting in a t(X;17) (p11.2;q25.3).…”

Reply to ‘Distinct ALK-rearranged and VCL-negative papillary renal cell carcinoma variants in two adults without sickle cell trait'

“…3 Consequently, two recently published large series of adult RCCs cumulatively identified four new ALK-rearranged tumors. 4,5 Current data, combined from four independent studies during 2010-2012, include six ALKrearranged tumors in a representative cohort of 884 RCCs of main morphologies arising in pediatric and adult patients of diverse ethnicities ( Table 1). …”

“…4,5 Further studies should clarify whether the molecular mechanism of clear-cell RCC governed by loss of VHL and ALK activation are mutually exclusive. Hereditary and some sporadic papillary RCCs are driven by MET tyrosine kinase, 6 and testing of both kinases in papillary RCCs appears to be rational especially because crizotinib combines anti-ALK and anti-MET activities.…”