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Gynecologic and Obstetric Pathology Therefore, It Was Investigated If TERT Promoter Mutations Could Be Used to Distinguish Sarcomatoid UC from IMT

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Gynecologic and Obstetric Pathology Therefore, It Was Investigated If TERT Promoter Mutations Could Be Used to Distinguish Sarcomatoid UC from IMT ANNUAL MEETING ABSTRACTS 271A sarcomatoid carcinoma; 1 lymphoepithelioma-like carcinoma and 1 adenoid cystic 1082 Spatial-Temporal Analysis of Urothelial Carcinoma for TERT carcinoma. Immunohistochemical profile for the UCa was CK7, CK5/6, CK903, p63, Promoter Mutations Thrombomodulin positive; CK20, CDX2 negative. P16 was positive in 67% (12/18) Xiaoyong Zheng, Jian Zhuge, John Fallon, Minghao Zhong. New York Medical College of UCas; GATA-3 was negative in 78% (14/18) of UCas. The 4 UCs were all positive at Westchester Medical Center, Valhalla, NY. for GATA-3 and two were positive for p16. Adenocarcinomas (8) have different Background: Urothelial carcinomas (UC) are well known for multifocality and immunohistochemical profiles: CK7 positive in all 8 cases; CK20 in 6; CDX2 in 5 and recurrence. Recent studies suggest that TERT promoter mutations could be a biomarker thrombomodulin in 2 cases. CK5/6 and p63 were negative in all 8 cases. All patients for the diagnosis or follow up urothelial carcinoma in urine. Therefore, the TERT underwent surgical excision. 22 patients had lymph node metastases (17 UCa; 5 promoter mutation status in those recurrent and multifocal urothelial carcinoma adenocarcinoma). 15 patients had distant metastases (12 UCa and 3 adenocarcinoma), are important information for the utility of TERT promoter mutations as urothelial with lung as the most common site. In addition to surgery, 22 patients had chemotherapy, carcinoma biomarker. 8 had radiation and 12 had chemoradiation. 114 patients had clinical outcome data, Design: For recurrent UC, we collected cases from 10 patients, 23 specimens. For with follow-up of 0.03 to 236.8 months (median: 19.7 months). 24 patients were alive multifocal UC, we collected cases from another 10 patients, 25 different tumor sits. All with no disease (median: 17 months); 35 patients were alive with disease (median: 20 slides were reviewed and selected to make sure that at least 20% of UC components are months); 28 patients died of disease (median survival: 11 months); 2 patients died of present. Macro-dissection was performed in some of cases. gDNA was extracted from other causes; 25 patients died of unknown causes. those tissue. TERT promoter mutations were detected by standard PCR-sequencing. Conclusions: Primary urethra carcinomas are rare, a majority having overlapping Results: For recurrent UC, specimens from 8/10 patients were positive for TERT morphological features and immunohistochemical profiles of UC and SCC. We propose promoter mutations, the rest of 2 were negative for the mutations. Importantly, the these should be called Urethral Carcinoma, rather than UC or SCC. PUC may behave mutation status were maintained in the recurrent UC. For multifocal UC, specimens from aggressively with lymph node and distant metastases with a short median survival time. 7/10 patients were positive for TERT promoter mutations, the rest of 3 were negative for the mutations. Again, the mutation status were maintained in theses multifocal UCs, too. 1080 Detecting Additional Chromosomal Translocations in TFE3 Conclusions: We found that TERT promoter mutations status keeps consistently in Translocation Renal Cell RCC By RNA-Seq recurrent and multifocal UC of the same individual. This indicates that carcinogenesis Xiaoyong Zheng, Yong Mao, Weihua Huang, Sitharthan Kamalakaran, Youfeng Yang, of recurrent and multifocal UC from the same individual are probably the same. W Marston Linehan, Maria J Merino, Minghao Zhong, Nevenka Dimitrova, John Importantly, TERT promoter mutation would be a good biomarker for the patient whose Fallon. New York Medical College at Westchester Medical Center, Valhalla, NY; previous UC were positive for the mutations. Philips Research North America, Briarcliff Manor, NY; National Cancer Institute, Bethesda, MD. 1083 Interobserver Reproducibility in Grading “Poorly Formed Glands” Background: TFE3 translocation renal cell carcinoma (RCC), officially accepted as Gleason Pattern 4 Prostate Cancer Among Urologic Pathologists as distinct subtype by 2004 WHO classification, is characterized by chromosomal Ming Zhou, Jianbo Li, Liang Cheng, Lars Egevad, Fang-Ming Deng, Lakshmi Kunju, translocations involving TFE3 gene (Xp11). As such, TFE3 translocation RCC has worse Cristina Magi-Galluzzi, Rohit Mehra, Jonathan Melamed, Savvas Mendrinos, Adeboye prognosis than other RCC subtypes. However, little is known about other chromosomal Osunkoya, Gladell Paner, Steven Shen, Kiril Trpkov, Toyonori Tsuzuki, Tian Wei, Ximing translocations or fusions in this particular RCC subtype. Therefore, it was investigated Yang, Rajal Shah. Gleason Grading Collaborative Group, New York, NY. if any other recurrent chromosomal translocations or fusions are associated with TFE3 Background: Gleason pattern 4 (GP4) prostate cancer (PCa) in needle biopsy is translocation RCC. critical for patient management and prognostication. The 2005 ISUP modified Gleason Design: RNA-seq has been performed on TFE3 translocation RCC cell lines: UOK109 grading system regards “poorly formed glands” as GP4. The diagnostic reproducibility and UOK145 for unbiased detection of chromosomal translocations including TFE3. All is unknown. potential translocations were detected with SOAPf------use [1] fusion detection pipeline Design: Digital images of 8 PCas representing a spectrum of well to poorly formed (Version 1.26) plus several layers of additional filters. More TFE3 translocation RCC glands were used to query 17 urologic pathologists for the definition of “poorly formed samples in TCGA (The Cancer Genome Atlas) RNA-seq database have been analyzed glands”. They were then asked to grade additional 23 PCa cases with poorly formed for additional translocations/fusions by the same method. glands as GP4 or not. These cases were classified into 9 sub-groups based on the number Results: PSF-TFE3 and NONO-TFE3 translocations have been detected in UOK 145 of poorly formed glands (<5, 5-10, >10 in each focus) and location (immediately and UOK109 cell lines, respectively. Onaverage, 1-2 translocations/fusions have been adjacent to, between and away from other well formed PCa glands) by two study authors identified in the cell lines and 7 cases from TCGA RNA-seq database. Among these before the study. A consensus diagnosis was defined as agreement by 75% participants. translocations/fusions, none of them are recurrent except TFE3 related translocations/ Results: Of 8 images queried for the definition of “poorly formed” glands, 5 attained fusions. consensus. Small cancer glands with rigid but well-formed lumens were not considered Conclusions: There are on average 1-2 translocations in TFE3 translocation RCC. “poorly formed”. Small glands with no discernible lumens, elongated glands with However, except TFE3 related translocations, none of them are recurrent. These compressed lumen and elongated small nests/cords with no discernible lumen were translocations may be more likely to be secondary/passenger events during the considered “poorly formed glands”. The interobserver agreement for the definition of carcinogenesis. This study further elucidates the important carcinogenic role of TFE3 “poorly formed glands” is fair (kappa=0.35). The diagnostic agreement in 23 ases was in this subtype RCC. fair (kappa=0.34) with 16 (70%) attained consensus. Focus with < 5 poorly formed [1]. Jia W, Qiu K, He M, Song P, Zhou Q, Zhou F, Yu Y, Zhu D, Nickerson ML, Wan S, glands regardless of their locations attained a consensus diagnosis of “not GP4” with a Liao X, Zhu X, Peng S, Li Y, Wang J, Guo G: SOAPfuse: an algorithm for identifying sensitivity, specificity and accuracy of 67% (4/6), 100% (10/10) and 88%, respectively. fusion transcripts from paired-end RNA-Seq data. Genome biology 2013, 14:R12. Focus with >10 poorly formed glands that are not immediately adjacent to other well- formed glands attained a consensus diagnosis of GP4 with a sensitivity, specificity and 1081 Distinguish Sarcomatoid Urothelial Carcinoma and Inflammatory accuracy of 60% (6/10), 100% (6/6) and 75% (12/16), respectively. The last 3 cases Myofibroblastic Tumor By TERT Promoter Mutations did not achieve a consensus as the poorly formed glands were at the edge of the biopsy Xiaoyong Zheng, Jian Zhuge, John Fallon, Ximing Yang, Minghao Zhong. New York specimens. Majority of participants (15/17) would grade poorly formed glands as GP4 Medical College at Westchester Medical Center, Valhalla, NY; Northwestern University, only when they retained poorly formed morphology in at least 2 levels. Feinberg School of Medicine, Chicago, IL. Conclusions: The agreement for grading “poorly formed” PCa glands as GP4 is only Background: Inflammatory myofibroblastic tumor (IMT) of the urinary bladder is fair among urologic pathologists. More studies are needed to better define “poorly an unusual spindle cell lesion that exhibits cytologic atypia, infiltrative growth, and formed” PCa glands. Focus with < 5 poorly formed glands regardless of their locations mitotic activity mimicking malignant tumors, such as sarcomatoid urothelial carcinoma is not diagnostic of GP 4. Focus with >10 poorly formed glands that are not immediately (UC). Most IMT are positive for cytokeratin. ALK reactivity was seen in 56% of cases. adjacent to other well-formed glands are diagnostic of GP4. In addition, Absent ALK expression was associated with a higher age overall, subtle histologic differences, and death from disease or distant metastases (in a younger subset). Recently, TERT promoter mutations appear
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