Naslov
Clinicopathological and molecular characterization of tubulocystic variants of renal tumors
(Clinicopathological and molecular characterization of tubulocystic variants of renal tumors)

Autori
Skenderi, Faruk

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, doktorska disertacija

Fakultet
Medicinski fakultet

Mjesto
Zagreb

Datum
17.09

Godina
2021

Stranica
80

Mentor
Ulamec, Monika ; Vranić, Semir

Ključne riječi
tubulocystic renal cell carcinoma ; renal oncocytoma ; papillary renal cell carcinoma ; chromophobe renal cell carcinoma ; immunophenotype

Sažetak
Renal tumors are a heterogeneous group of neoplasms recently subjected to intensive research, resulting in several new entities and reclassification. Therefore, we aimed to characterize the morphological features, immunoprofile, and molecular genetic profile of a new entity, namely the tubulocystic renal cell carcinoma. Additionally, we aimed to characterize tubulocystic/cystic variants of selected common renal tumor subtypes and determine the most useful properties for the differentiation of these tumors in diagnostic practice. Finally, we aimed to evaluate the effect of tubulocystic histological pattern on the patients' survival. We selected 24 renal oncocytomas (RO), 10 papillary renal cell carcinomas (PRCC), 10 chromophobe renal carcinomas (ChRCC), and 15 tubulocystic renal cell carcinomas (TCRCC) with a predominantly (more than 50%) cystic architecture and compared them with a control cohort of their conventional counterparts. We used light microscopy, immunohistochemistry, array comparative genomic hybridization, PCR, and Sanger sequencing to evaluate the tumors for morphology, immunophenotype, chromosomal aberrations, and mutational analyses. Tubulocystic renal cell carcinoma showed distinctive pathological and molecular characteristics and is a separate tumor entity. Nevertheless, 5/11 TCRCC cases were associated with PRCC-like, high grade or CCPRCC/RAT-like areas, and cases with high grade or RAT-like morphology showed less favorable outcomes. Immunohistochemically, TCRCC showed diffuse staining for CAM5.2, MIA, OSCAR ; vimentin and AMACR mainly were positive ; EMA and CA-IX showed variable positivity ; CD117 was negative in 93.3% of cases, and average Ki-67 proliferative index was 17.93. Gain of chromosomes 7, 17 and Y was present but not consistently found across the cases. Cystic variants of RO, PRCC, ChRCC show similar immunophenotype and molecular genetic characteristics compared to their conventional counterparts. The most valuable antibodies in diagnosing cystic renal tumors are AMACR, CK7, CAIX, CD117, Vimentin, CD10, and Ki67 in combination with tumor morphology. Overall survival plots of Cystic RO vs. conventional RO at 60 months were similar, and the difference was not significant (p=0.98). Overall survival for TCRCC at 60 months reveals an excellent prognosis of this tumor TRCC. The overall survival rate of cystic PRCC is more favorable than conventional PRCC ; however, the difference was not statistically significant (p=0.881). The overall survival rate of cystic ChRCC shows a more favorable outcome for these patients compared to conventional ChRCC, but the difference was not statistically significant (p=0.667). Molecular genetic alterations in renal tumors are heterogeneous, ranging from none detected to multiple chromosomal gains or losses.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA