The Clinicopathologic Features Of Adult Xp11.2 Translocation Renal Cell Carcinoma

Objections: Xp11.2 translocation /TFE3 gene fusion associated renal cell carcinoma(Xp11.2 RCC)was a rare type of renal cell carcinoma(RCC).Owning to lack of typical morphological features,Xp11.2 RCCs were usually misdiagnosed as other conventional types,such as clear cell renal cell carcinoma(cc RCC),papillary renal cell carcinoma(p RCC),chromophobe renal cell carcinoma(Ch RCC)and so on.Typically,immunohistochemistry(IHC)and fluorescence in situ hybridization(FISH)were the routine methods in the diagnosis of Xp11.2 RCC.In this way,our study aims at(1)evaluating the advantages and disadvantages of IHC and FISH after the screening of Xp11.2 RCC,and(2)exploring the clinicopathological characteristics between Xp11.2 RCC and non-xp11.2 RCC by comparing their clinicopathological data.Methods: Between January 2016 to January 2019,all RCC patients with complete clinicopathological data were retrospective analyzed.The target areas of donor blokes were marked after each hematoxylin and eosin(HE)stained slides were review.Specimens on tissue microarrays were extracted from above target areas by a needle core,and were then put into the prepared blank paraffin to construct tissue chips of 5×8 lattice.After the tissue microarrays were secondary embedded,three successive slices of 3 mm thick were cut and mounted on the prepared slides.HE staining,TFE3 IHC and FISH were repetitively performed on three sections of each cases.For suspicious cases,which were strong nuclear immunoreactive to TFE3 or positive to TFE3 split probe,four to six pieces of successive slices of 10 mm thick were cut.Followed with total ribonucleic acid(RNA)extraction and reverse transcription,polymerase chain reaction(PCR)amplification was carried out with multiple PCR primers.Deoxyribonucleic acid(DNA)fragments from agarose gels were pacified and were then verified by Sanger sequencing.At last,the clinicopathological characteristics of Xp11.2 RCC verified by PCR and non-Xp11.2 RCC were compared.Results: From January 2016 to January 2019,428 patients underwent radical nephrectomy(RN)or nephron-sparing surgery(NSS).In this way,a total of 11 tissue chips were produced.Four arrays were found lost by HE staining while the other 424 arrays were integrated or slight shift,thus effective rate of tissue chip reached up to 99.07%.Among the effective arrays,34/424(8.0%)cases were immunoreactive to TFE3 and 27/34(79.4%)cases were found IHC positive but FISH negative.Seven cases positive to FISH were eventually identified as Xp 11.2 RCC,accounting 1.7% of the whole RCC population.Among those with TFE3 fusion gene,each of two cases were ASPL-TFE3 fusion and SFPQ-TFE3 fusion,and 3 cases were PRCC-TFE3 fusion.The sensitivity and specificity of IHC were 100% and93.5%,respectively.Among those Xp11.2 RCC patients,there were 5 females(71.4%)and2 males(28.6%).The average age were 49.71 ± 9.41 years old,and the average tumor diameter were 5.61 ± 2.51 cm.Six out of seven cases(85.7%)presented with flank pain or gross hematuria.RN were performed on six patients and NSS were performed on one case.Postoperative pathology revealed p T1 two cases,p T2 one case,p T3 and p T4 each of two cases.Renal vein,pelvis and renal sinus invasion were respectively identified in 3 cases,3cases and 4 cases.Two cases of lymph nodes involvement and four cases of distance metastasis were found.All cases got satisfied following up ranged from 14 to 42 months.The 3-year progression-free survival(PFS)and overall survival(OS)were 42.85% and71.43%,respectively.Compared with non-Xp11.2 RCC,Xp11.2 RCC trended to present gross hematuria and flank pain.The incidences of advanced nuclear grade,lymph node metastasis,renal vein invasion and renal sinus invasion in the set of Xp11.2 RCC were significantly higher than that of non-Xp11.2 RCC(P<0.05).In addition,the 3-year PFS of Xp11.2 RCC is significantly lower than the population of non-Xp11.2 RCC(P<0.05).Conclusions: With the feature of superior sensitivity and high false positives rate,TFE3 IHC should be used in the screening of Xp11.2 RCC.FISH is still the gold standard in identifying diagnosis.In general,Xp11.2 RCC trends to affected female at middle-aged.Flank pain or gross hematuria were frequently presented among Xp11.2 RCC.Compared with non-Xp11.2 RCC,Xp11.2 RCC shares a more aggressive and invasive progresses.Adult cases trend to be local invasion and distant metastasis,and the long-term prognosis is usually unsatisfied.