Il carcinoma renale papillare a cellule chiare e il carcinoma renale con stroma leiomuscolare sono due entit\ue0 recentemente descritte in letteratura, a comportamento biologico non aggressivo e composte da elementi a citoplasma chiaro e basso grado nucleare, la cui distinzione dai principali istotipi renali e in particolare dal carcinoma renale a cellule chiare di tipo convenzionale risulta spesso complessa.
In questa tesi sono stati studiati 14 carcinomi renali papillari a cellule chiare e 7 carcinomi renali con stroma leiomuscolare, utilizzando un ampio pannello immunoistochimico e diverse metodiche di biologia molecolare, allo scopo di definirne maggiormente i caratteri comuni e permettere una loro distinzione pi\uf9 efficace dai pi\uf9 comuni istotipi tumorali renali.
Entrambe le entit\ue0 descritte hanno presentato diffusa espressione di CK7, CAIX e costante negativit\ue0 per AMACR. E\u2019 stata inoltre evidenziata la frequente positivit\ue0 per i marcatori 34\u3b2E12 e GATA3. I tumori hanno evidenziato inoltre un profilo genetico stabile, l\u2019assenza di alterazioni del gene VHL e di perdita del cromosoma 3p. Un solo caso, con caratteristiche morfologiche e in parte immunofenotipiche e genetiche del gruppo dei carcinomi renali papillari a cellule chiare, ha presentato negativit\ue0 per 34\u3b2E12, GATA3 e presenza di alterazioni a carico del gene VHL ed \ue8 pertanto stato riclassificato come carcinoma renale a cellule chiare.
L\u2019insieme dei caratteri descritti, comuni ai carcinomi renali papillari a cellule chiare e a quelli con stroma leiomuscolare, permettono di distinguerli dagli istotipi renali \u201cconvenzionali\u201d e di ipotizzare una loro origine comune. Tuttavia, la presenza di casi con caratteri in parte sovrapponibili al carcinoma renale a cellule chiare sottolinea la necessit\ue0 dell\u2019utilizzo di pi\uf9 metodiche diagnostiche per loro il riconoscimento nella pratica clinica.Clear cell papillary renal cell carcinoma (CCPRCC) is renal neoplasm that has been recently proposed to be added to the current WHO classification of renal tumors. We collected and described a series of these neoplasms, in order to get insights to their clinico-pathological and molecular profiles.
We identified 14 CCPRCC. A first level of Immunohistochemical analysis was performed using CK7, CD10, AE1/AE3, alpha-methylacyl-CoA racemase, PV, S100A1, \u3b1-SMA, caldesmon and desmin. We also performed FISH analysis using probes for chromosome 3 and 3p25, array CGH, VHL sequencing and methylation analysis on a part of the cases. Than with a second level of immunoistochemical analysis, we investigated the immunoexpression of 34\u3b2E12, CK1, CK5, CK10, CK14 and GATA3, looking for specific markers.
The mean age of the patients was 61, including 9 males and 5 females. The average tumor diameter was 2,62 cm. CCPRCC presented a thick encapsulation and a tubule-papillary or tubule-cystic morphology composed of clear cells with low-grade nuclei. With the first level of immunoistochemical analyses all cases were positive for CK7 and AE1-AE3 and negative for P504S, Parvalbumin, HMB45 and cathepsin K; 75% and 62% of cases were positive respectively for CD10 and S100A1. No deletion of chromosome 3p, significant VHL methylation or changes in copy number was detected in any case, whereas only one CCPRCC showed VHL mutation and presented deletions in chromosome 3 and 6 at CGH analysis.
The second level immunoistochemical analysis showed that 13 of 14 cases of CCPRCC express 34\u3b2E12. The immunoexpression of CK14 had the same result of 34\u3b2E12. All cases were negative for Ck1 and CK10; only 4 cases of CCPRCC were positive for CK5. GATA3 was expressed in 7 of 13 (54%) cases of CCPRCC.
Comparing as control the immunoexpression of 292 cases of conventional clear cell RCC 34\u3b2E12 (or CK14) was expressed in 0,3% and GATA3 was expressed in 1% of the cases giving to them a strong specific meaning.
We concluded that CCPRCC show strong and diffuse positivity for CK7 and do not show 3p deletion, VHL mutation or methylation abnormalities. These tumors show a genomic stability after wide whole genomic analysis.
We propose the immunoistochemical markers 34\u3b2E12 (or CK14) and GATA3 as specific markers useful for the identification of these distinct renal neoplasms
