scholarly journals Ιστική μελέτη στην επιθήλιο-μεσεγχυματική μετατροπή σε νεφροκυτταρικό καρκίνωμα

2021 ◽  
Author(s):  
Γρηγόριος Θεοδωρόπουλος
Keyword(s):  
Clear Cell ◽  
Chromophobe Rcc ◽  
Grade Classification ◽  
Papillary Rcc ◽  
Clear Cell Rcc

Το φαινόμενο της επιθηλιομεσεγχυματικής μετατροπής είναι η διεργασία κατά την οποία ένα επιθηλιακό κύτταρο αποκτά φαινότυπο μεσεγχυματικού κυττάρου. Η μετατροπή αυτή στον φαινότυπο του επιθηλιακού κυττάρου απαιτεί την δημιουργία ενός νέου μοριακού προγράμματος του επιθηλιακού ιστού με νέες βιοχημικές οδηγίες. Η ΕΜΤ συμμετέχει σε φυσιολογικές καθώς και σε παθολογικές διεργασίες του οργανισμού. Σκοπό της παρούσας ερευνητικής δραστηριότητας αποτέλεσε η διερεύνηση της ανοσοιστοχημικής πρωτεινικής συνέκφρασης των μορίων ε-καντχερίνης και βιμεντίνης σε σειρά καρκινωμάτων νεφρού διάφορης ιστολογικής τυποποίησης και η συσχέτισή τους με τα κλινικοεργαστηριακά χαρακτηριστικά τους γνωρίσματα. Το υλικό αναδύθηκε από την αρχειακή ιστική βάση του Παθολογο-ανατομικού Τμήματος του Γενικού Νοσοκομείου Αθηνών ‘’ΕΛΠΙΣ’’ και αφορούσε σε - εμπεδωμένα σε κύβους παραφίνης – εκατό (n=100) σποραδικά πρωτοπαθή καρκινώματα νεφρού (RCC), προιόντα νεφρεκτομής. Παθολογοανατομικά ταξινομημένα σύμφωνα με τα ιστολογικά κριτήρια της WHO και όσον αφορά τη διαφοροποίηση βαθμονομημένα με το σύστημα κατά Furhman. Τα εξετασθέντα καρκινώματα αφορούσαν σε 75 διαυγοκυτταρικού τύπου (clear cell RCC), 13 θηλώδους τύπου (papillary RCC) και 12 χρωμόφοβου τύπου (chromophobe RCC). Σύμφωνα με τη συνδυασμένη συμβατική και ψηφιακή ανάλυση, υποέκφραση ή απώλεια της έκφρασης της ε-καντχερίνης παρατηρήθηκε σε 52 περιπτώσεις (52%), ενώ οι υπόλοιπες 48 (48%) χαρακτηρίστηκαν από μετρίου εώς ισχυρού βαθμού ανοσοέκφραση. Όσον αφορά τον ιστολογικό τύπο των εξετασθέντων περιστατικών, απώλεια της έκφρασης της ε-καντχερίνης συσχετίσθηκε περισσότερο με τα διαυγοκυτταρικά και θηλώδους τύπου (p=0.001). Ενδιαφέρουσα παρατήρηση αποτελεί ακόμη η προοδευτική απώλεια της έκφραση του μορίου σε σχέση με το βαθμό διαφοροποίησης του νεοπλάσματος κατά ταξινόμηση Fuhrman’s grade classification (p=0.002). Yποέκφραση ή απώλεια της έκφρασης της βιμεντίνης παρατηρήθηκε σε 19 περιπτώσεις (19%), ενώ οι υπόλοιπες 81 (81%) χαρακτηρίστηκαν από μετρίου εώς ισχυρού βαθμού ανοσοέκφραση. Όσον αφορά τον ιστολογικό τύπο των εξετασθέντων περιστατικών, απώλεια της έκφρασης της βιμεντίνης συσχετίσθηκε περισσότερο με τα διαυγοκυτταρικά και θηλώδους τύπου (p=0.001).

scholarly journals Detection of a peritumoral pseudocapsule in patients with renal cell carcinoma undergoing robot-assisted partial nephrectomy using enhanced MDCT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Makoto Toguchi ◽  
Toshio Takagi ◽  
Yuko Ogawa ◽  
Satoru Morita ◽  
Kazuhiko Yoshida ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Partial Nephrectomy ◽  
Renal Cell ◽  
Clear Cell ◽  
Robot Assisted ◽  
High Attenuation ◽  
Papillary Rcc ◽  
Clear Cell Rcc

AbstractTo investigate the detection of peritumoral pseudocapsule (PC) using multi-detector row computed tomography (MDCT) for tumors resected by robot-assisted laparoscopic partial nephrectomy (RAPN) for T1 renal cell carcinoma (RCC). Study participants included 206 patients with clinical T1 RCC who underwent RAPN between October 2017 and February 2018. Two radiologists who were blinded to the pathological findings evaluated the computed tomography (CT) images. Radiological diagnosis of a PC was defined by a combination of observations, including a low-attenuation rim between the tumor and renal cortex in the cortico-medullary phase and a high-attenuation rim at the edge of the tumor in the nephrogenic or excretory phase. A PC was detected on CT in 156/206 tumors (76%) and identified by pathology in 182/206 (88%) tumors including 153/166 (92%) clear cell RCC, 13/14 (93%) papillary RCC, and 7/16 (44%) chromophobe RCC. In the whole cohort, CT findings showed a sensitivity of 81.3% (148/182), specificity of 66.7% (16/24), and positive predictive value of 94.9% (148/156). When the data were stratified according to pathological subtypes, MDCT was observed to have a sensitivity of 86.9% (133/153) and specificity of 61.5% (8/13) in clear cell RCC, sensitivity of 38.5% (5/13) and specificity of 100% (1/1) in papillary RCC, and sensitivity of 44.4% (4/7) and specificity of 66.7% (6/9) in chromophobe RCC. A low or high-attenuation rim around the tumor in the cortico-medullary or nephrographic-to-excretory phase indicates a PC of RCC, though the accuracy is not satisfactory even with 64- or 320-detector MDCT.

WITH INCREASING TUMOUR SIZE HISTOPATHOLOGICAL FEATURES ARE MORE AGGRESSIVE IN CLEAR CELL RCC, BUT NOT IN PAPILLARY RCC

2006 ◽  
Vol 5 (2) ◽  
pp. 257
Author(s):  
M. Remzi ◽  
C. Seitz ◽  
M. Özsoy ◽  
E. Tanovic ◽  
H.C. Klingler ◽  
...  
Keyword(s):  
Clear Cell ◽  
Tumour Size ◽  
Histopathological Features ◽  
Papillary Rcc ◽  
Clear Cell Rcc

Chromophobe Renal Cell Carcinoma With Retrograde Venous Invasion and Gain of Chromosome 21: Potential Harbingers of Aggressive Clinical Behavior

2018 ◽  
Vol 26 (6) ◽  
pp. 536-541 ◽  
Author(s):  
Mohsin Jamal ◽  
Kanika Taneja ◽  
Sohrab Arora ◽  
Ravi Barod ◽  
Craig G. Rogers ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Aggressive Behavior ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Renal Vein ◽  
Clear Cell ◽  
Venous Invasion ◽  
Chromosome 21 ◽  
Chromophobe Rcc ◽  
Clear Cell Rcc

Occasionally, renal cell carcinoma (RCC) with renal vein extension spreads against the flow of blood within vein branches into the kidney, forming multifocal nodules throughout the renal parenchyma. These foci are not regarded as multiple tumors but rather reverse spread of tumor along the venous system. This intravascular spread has previously been reported in clear cell RCC and RCC unclassified. However, to our knowledge, this has never been reported in chromophobe RCC. Chromophobe RCC is a unique histologic subtype of renal cancer, generally thought to have less aggressive behavior. However, it nonetheless has the potential to undergo sarcomatoid dedifferentiation, which is associated with poor prognosis. We report a unique case of a 65-year-old man with chromophobe RCC (pT3a) showing classic morphology (nonsarcomatoid), yet presenting with retrograde venous invasion and hilar lymph node metastasis at the time of right radical nephrectomy. Fluorescence in situ hybridization revealed gain of chromosome 21 with loss of multiple other chromosomes. Partial hepatectomy was performed to resect metastatic RCC 7 months after nephrectomy, revealing chromophobe RCC with classic morphology. Bone biopsy confirmed skeletal metastases 38 months after initial diagnosis. Although invasion of the renal vein and retrograde venous invasion are characteristically seen in clear cell RCC, this unusual phenomenon may also occur in chromophobe RCC, despite its unique tumor biology. This and gain of chromosome 21, which was postulated to be associated with aggressive behavior in a previous report, were associated with adverse behavior in our patient, who had short-term progression to multi-organ metastatic disease.

scholarly journals Comparative Assessment of the WNT/β-Catenin Pathway, CacyBP/SIP, and the Immunoproteasome Subunit LMP7 in Various Histological Types of Renal Cell Carcinoma

2020 ◽  
Vol 10 ◽  
Author(s):  
Żaneta Piotrowska ◽  
Michał Niezgoda ◽  
Grzegorz Młynarczyk ◽  
Magdalena Acewicz ◽  
Irena Kasacka
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Kidney Tissue ◽  
Renal Tumors ◽  
Histological Types ◽  
Chromophobe Rcc ◽  
Study Results ◽  
Clear Cell Rcc

ObjectiveThe Wnt/ß-catenin pathway plays an important role in pathogenesis of variety cancers. Most studies on changes in WNT/β-catenin pathway in renal cell carcinoma (RCC) apply only to clear cell RCC, while there are no comparative assessments of this signaling pathway in various histological types of renal tumors in the available literature. Additionally, considering the close relationship between WNT/β-catenin signaling, CacyBP/SIP and proteasomal activity, it seemed worth comparing WNT/β-catenin pathway, CacyBP/SIP and LMP7 immunoproteasome subunit in human samples of clear cell, papillary, and chromophobe RCC.MethodsTests were performed on sections of three types of kidney tumors together with surrounding unchanged tissue fragments collected from 50 patients. Samples were divided into three groups depending on the histological type of cancer: clear cell, papillary and chromophobe RCC. Immunohistochemistry and PCR methods were used to identify WNT10A, Fzd5, β-catenin, GSK-3ß, CacyBP/SIP, LMP7, and gene expression.ResultsImmunoreactivity and expression of WNT10A, Fzd5, β-catenin, GSK-3ß, CacyBP/SIP, LMP7 in clear cell RCC was markedly increased compared to non-cancerous kidney tissue. In papillary RCC, immunoreactivity and expression of WNT/β-catenin pathway, CacyBP/SIP, LMP7 was also increased compared to non-malignant kidneys, but it was less pronounced than in clear cell RCC. The least substantial increase in immunoreactivity and expression of WNT/β-catenin pathway, CacyBP/SIP, LMP7 was found in chromophobe RCC, compared to other RCC histological subtypes studied.ConclusionsStudy results suggest an important role of WNT/β-catenin pathway, CacyBP/SIP and LMP7 in RCC carcinogenesis, and may indicate new aspects of pathomechanisms leading to differences in the biology of clear cell, papillary and chromophobe RCC.

Multicenter prospective phase II study of sunitinib in non-clear cell type renal cell carcinoma.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 325-325 ◽  
Author(s):  
J. Lee ◽  
J. Ahn ◽  
H. Lim ◽  
S. Lee ◽  
T. Kim ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Clear Cell ◽  
Progression Free Survival ◽  
High Response Rate ◽  
Drop Out ◽  
Eligibility Criteria ◽  
Steroid Dependence ◽  
Chromophobe Rcc ◽  
Clear Cell Rcc

325 Background: Sunitinib has been shown to produce a high response rate (RR), and improved progression-free survival (PFS) in patients (pts) with clear cell RCC. Retrospective data suggest sunitinib may be effective in papillary and chromophobe RCC. We conducted a multicenter phase II trial of sunitinib in non-clear cell RCC (nccRCC). Methods: Eligibility criteria included PS 0-1, measurable disease, and adequate organ function. Pts with brain metastases were not excluded if controlled without steroid dependence. Response assessment was performed every 6 weeks. Primary endpoint was RR. Secondary endpoints were TTP, safety and OS. Results: Between 6/2008 and 7/2010, 29 pts with nccRCC were enrolled (total accrual 35: P0=5%, P1=20%, alpha=0.05, beta=0.2, drop-out rate 15%). Median age was 52 (18–76). Twenty-four pts (84%) had prior nephrectomy. Seven pts (24%) had poor risk and 13 (45%) had intermediate risk disease by MSKCC criteria. Twenty-one pts had papillary RCC (type II in 11 and type not- specified in 10), and 4 patients had chromophobe RCC. Two pts discontinued protocol treatment due to toxicity prior to completion of cycle 1 (one pt had cardiogenic shock 27 days after start of therapy and the other refused further treatment 5 days after therapy). Eleven pts out of 29 had partial response with a RR of 38% (95% CI, 20.2%–55.6%) and additional 15 patients (52%) had SD with a disease control rate of 90%. Response rates were not significantly different according to the histologic type (43% in papillary type and 25% in chromophobe type). Median duration of response was 12.7 months (95% CI, 2.3∼23.1) and median TTP was 6.4 months (95% CI, 4.5∼8.3). With a median FU duration of 16 months (95% CI, 8.6∼23.4), 10 pts have been dead resulting in an estimated median OS of 17.9 months. Toxicity profiles were commensurate with prior reports on Korean patients (Yoo, et al. Jpn J Clin Oncol 2010). However, there was one treatment-related death caused by acute heart failure in patient without relevant risk factors for heart disease. Conclusions: Although our study is ongoing, the primary endpoint has been met and these data suggest that suntinib has promising activity in patients with nccRCC. No significant financial relationships to disclose.

Safety and efficacy of MET inhibitor tivantinib (ARQ 197) combined with sorafenib in patients (pts) with renal cell carcinoma (RCC) from a phase I study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4545-4545 ◽  
Author(s):  
Igor Puzanov ◽  
Jeffrey Alan Sosman ◽  
Armando Santoro ◽  
Robert E. Martell ◽  
Grace K. Dy ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase I ◽  
Dose Escalation ◽  
Clear Cell ◽  
Single Agent ◽  
Vegf Receptor ◽  
Chromophobe Rcc ◽  
Best Response ◽  
Met Inhibitor ◽  
Clear Cell Rcc

4545 Background: Inhibitors of vascular endothelial growth factor (VEGF) and VEGF receptor are standard therapy for RCC, and the MET signaling pathway is implicated in tumor angiogenesis. Tivantinib is an oral, selective MET inhibitor. In several tumor models, tivantinib plus sorafenib exhibited synergistic antitumor activity vs single-agent activity. This phase I dose-escalation study assessed the safety of tivantinib plus sorafenib in pts with advanced solid tumors. Methods: Endpoints were safety, the recommended phase II dose (RP2D) of tivantinib plus sorafenib, and antitumor activity. Previously, dose escalation established the RP2D as tivantinib 360 mg twice daily (BID) plus sorafenib 400 mg BID. Extension cohorts enrolled ≤ 20 pts each with RCC or other tumors. Patients were treated until disease progression or unacceptable toxicity. Results: 20 pts (mean age, 60 yr) including 16 clear cell, 3 papillary, and 1 clear cell/chromophobe RCC pts received treatment at the RP2D (n = 19) or tivantinib 360 mg BID plus sorafenib 200 mg BID (n = 1). 4 pts are still on study. 16 pts (13 with clear cell RCC) received ≥ 1 previous systemic therapy (median, 2; range, 0-4) including VEGF (14 pts) and/or mTOR (5 pts) inhibitors. The most common (≥ 25%) adverse events were rash (65%), diarrhea (45%), alopecia (40%), hypophosphatemia (35%), and fatigue, stomatitis, palmar-plantar erythrodysesthesia syndrome, and pruritus (25% each). Best response was partial response (PR) in 3 pts (all clear cell RCC pts) and stable disease (SD) in 15 pts (11 clear cell, 3 papillary, and 1 clear cell/chromophobe RCC pts). 7 pts with SD had ≥ 10% tumor size reduction. The overall response rate (ORR) and disease control rate (DCR; PR + SD) were 15% and 90%, respectively. Median progression-free survival (mPFS) was 12.7 mo (95% CI, 7.1-14.5 mo). In 14 pts previously treated with a VEGF inhibitor, best response was 2 PR and 10 SD, the ORR and DCR were 14% and 86%, respectively, and mPFS was 12.7 mo (95% CI, 5.3-NR mo). Conclusions: Oral combination therapy with tivantinib plus sorafenib was well tolerated and exhibited preliminary anticancer activity in pts with RCC, including pts pretreated with VEGF inhibitors.

Patients with metastatic papillary renal cell carcinoma (RCC) who may benefit from sunitinib therapy (tx): Results from an international metastatic RCC database.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 486-486 ◽  
Author(s):  
Daniel Kejzman ◽  
Maya Gottfried ◽  
Natalie Maimon ◽  
Hans J. Hammers ◽  
Mario A. Eisenberger ◽  
...  
Keyword(s):  
Cox Regression ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Papillary Renal Cell Carcinoma ◽  
Active Smoking ◽  
Factors Associated ◽  
Clinicopathologic Factors ◽  
Papillary Rcc ◽  
Clear Cell Rcc ◽  
Pre Treatment

486 Background: The VEGFR inhibitor sunitinib is a standard tx for metastatic clear cell RCC. Data on the activity of sunitinib in metastatic non clear cell RCC, is limited by small or heterogeneous (mixed histology or targeted therapies) studies, that revealed a lower antitumor activity than in patients with clear cell histology. We aimed to analyze the activity of sunitinib in a large international cohort of patients with metastatic papillary RCC, and to characterize patients who may benefit for this therapy. Methods: Records from metastatic papillary RCC patients treated with sunitinib in 10 centers across 3 countries were retrospectively reviewed. Univariate and multivariate analyses of association between clinicopathologic factors and clinical outcome were performed using Cox regression. Results: Between 2004-2013, 74 patients (median age 60, 68% male) with metastatic papillary RCC were treated with sunitinib. 78% had a prior nephrectomy. HENG risk was good 11%, intermediate 56%, and poor 33%. 21% were active smokers, and 31% users of angiotensin system inhibitors. 24% and 41% had liver and bone metastases, respectively. 55% had a pre-treatment neutrophil to lymphocyte ratio (NLR) >3. 40% had dose reduction/treatment interruption. Sunitinib induced hypothyroidism and hypertension (HTN) occurred in 30% and 43%, respectively. 70% achieved a clinical benefit (partial response + stable disease), while 30% had disease progression within the first 3 months of therapy. Median progression free survival (PFS) and overall survival (OS) were 5 and 12 months, respectively. 27% had a PFS ≥ 1 year, and 26% survived ≥ 2 years. Factors associated with PFS were sunitinib induced HTN (HR 0.31, p=0.002), pre-treatment NLR >3 (HR 5.3, p=0.001), and active smoking (HR 2.5, p=0.01). Factors associated with OS were sunitinib induced hypothyroidism (HR 0.4, p=0.024), past nephrectomy (HR 0.41, p=0.02), pre-treatment NLR >3 (HR 2.25, p=0.036), and active smoking (HR 2.3, p=0.027). Conclusions: Clinicopathologic factors may be used to identify patients with metastatic papillary RCC who may benefit from sunitinib tx. A prolonged PFS and OS were noted in 26-27% of patients.

Immunohistochemical analysis of kallikrein-related peptidases in the normal kidney and renal tumors: potential clinical implications

2010 ◽  
Vol 391 (4) ◽  
Author(s):  
Manal Gabril ◽  
Nicole M. White ◽  
Madeleine Moussa ◽  
Tsz-fung F. Chow ◽  
Shereen M. Metias ◽  
...  
Keyword(s):  
Clear Cell ◽  
Prognostic Significance ◽  
Immunohistochemical Analysis ◽  
Renal Tumors ◽  
Low Grade ◽  
High Grade ◽  
Cytoplasmic Staining ◽  
Chromophobe Rcc ◽  
Clear Cell Rcc ◽  
Granular Cytoplasmic Staining

Abstract Kallikrein-related peptidases (KLKs) have been shown to be differentially expressed in various malignancies and shown to be useful tumor markers. Previous immunohistochemistry (IHC) analysis demonstrated that KLKs 5, 6, 10, and 11 have a potential prognostic significance in renal cell carcinoma (RCC). To further explore the significance of KLKs, we examined KLKs 1, 6, 7, and 15 in different subtypes of renal tumors. KLK1 has stronger expression in high grade compared to low grade clear cell RCC. However, KLK6 and KLK7 show strong expression in low grade in contrast to high grade clear cell RCC. Furthermore, the expression of KLK7 can distinguish between oncocytoma and chromophobe RCC. Oncocytoma showed diffuse, strong granular cytoplasmic staining, but chromophobe RCC showed focal weak homogeneous cytoplasmic stain. The pattern of staining of different KLKs can also be helpful in differentiating some of the subtypes of renal tumors. Our results show the potential ability of KLKs to serve as diagnostic markers and expand previous data about the prognostic significance of KLKs in kidney cancer. In addition, our study is the first to show the ability of KLK staining to distinguish various types of kidney cancers when morphology is similar.

scholarly journals Development of Pathological Diagnostics of Human Kidney Cancer by Multiple Staining Using New Fluorescent Fluolid Dyes

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Dilibaier Wuxiuer ◽  
Yun Zhu ◽  
Takunori Ogaeri ◽  
Keiji Mizuki ◽  
Yuki Kashiwa ◽  
...  
Keyword(s):  
Room Temperature ◽  
Clear Cell ◽  
Human Kidney ◽  
Renal Tumors ◽  
Renal Angiomyolipoma ◽  
Renal Tubules ◽  
Cell Renal Cell Carcinoma ◽  
Fluorescent Markers ◽  
Chromophobe Rcc ◽  
Papillary Rcc

New fluorescent Fluolid dyes have advantages over others such as stability against heat, dryness, and excess light. Here, we performed simultaneous immunostaining of renal tumors, clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, acquired cystic disease-associated RCC (ACD-RCC), and renal angiomyolipoma (AML), with primary antibodies against Kank1, cytokeratin 7 (CK7), and CD10, which were detected with secondary antibodies labeled with Fluolid-Orange, Fluolid-Green, and Alexa Fluor 647, respectively. Kank1 was stained in normal renal tubules, papillary RCC, and ACD-RCC, and weakly or negatively in all other tumors. CK7 was positive in normal renal tubules, papillary RCC, and ACD-RCC. In contrast, CD10 was expressed in renal tubules and clear cell RCC, papillary RCC, AML, and AC-RCC, and weakly in chromophobe RCC. These results may contribute to differentiating renal tumors and subtypes of RCCs. We also examined the stability of fluorescence and found that fluorescent images of Fluolid dyes were identical between a tissue section and the same section after it was stored for almost three years at room temperature. This indicates that tissue sections can be stored at room temperature for a relatively long time after they are stained with multiple fluorescent markers, which could open a door for pathological diagnostics.

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