Correlation of insulin-receptor expression with efficacy of axitinib in patients with advanced renal cell carcinoma.

442 Background: Axitinib has demonstrated high efficacy with well-controlled adverse events (AEs) for advanced renal cell carcinoma (RCC). Recently, nivolumab has been approved for advanced RCC. However, it is very expensive in Japan and may cause severe immune-related AEs. There is no clue to choose axitinib or nivolumab as the second-line for advanced RCC. Previously we identified the gene set which may predict poor prognosis of RCC patients (Takahashi m et.al., Proc Natl Acad Sci U S A., 98: 9754, 2001) and have sought to elucidate whether insulin receptor (INSR) expression in the gene set may predict the resistance for axitinib as a biomarker. Methods: Axitinib was administered in 36 patients in our department between January 2008 and April 2015. Median age was 70 (36-84) years old with 22 males and 14 females. Histological subtype included clear cell RCC (n=27, 75.0%), clear cell + sarcomatoid component (n=3), collecting duct carcinoma (n=2), papillary, sarcomatoid, mucinous tubular and spindle cell carcinoma (MTSCC), and unknown in each one. Axitinib was administered in two patients as the first line, 21 patients as the second line, and 13 patients as ≥ the third line. Tissue of primary tumor was available in 20/36 patients, including 16 clear cell RCC and 4 other subtypes. Immunohistochemical INSR expression was examined and correlated with survival of the patients with axitinib. Results: Objective response rate was 27.6%, progression-free survival (PFS) was 16.3 months, and overall survival (OS) was 41.9 months in clear cell RCC patients. Patients with low INSR expression (n=7) had significantly shorter PFS (68 vs. 586 days, p<0.001) and OS (169 vs. 1027 days, p=0.004) compared with those with high INSR expression (n=13). If only clear cell RCC was evaluated, patients with low INSR expression (n=3) had significantly shorter PFS (77 vs. 586 days, p=0.008) and OS (294 vs. 1027 days, p=0.016) compared with those with high INSR expression (n=13). Conclusions: Axitinib was highly effective for advanced clear cell RCC. However, immunohistochemically low expression of INSR in the primary tumor may predict the resistance for axitinib and those patients may be more suitable for immune checkpoint inhibitors.

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Faculty Opinions recommendation of Response of the primary tumor to neoadjuvant sunitinib in patients with advanced renal cell carcinoma.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1147883.604974 ◽

2009 ◽

Author(s):

Keith Flaherty ◽

Stephen Keefe

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Primary Tumor ◽

Renal Cell ◽

Advanced Renal Cell Carcinoma

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Two Cases of Sporadic Eosinophilic Solid and Cystic Renal Cell Carcinoma in Manitoba Population

International Journal of Surgical Pathology ◽

10.1177/1066896921993229 ◽

2021 ◽

pp. 106689692199322

Author(s):

Seyed Mohammad Mohaghegh Poor ◽

Shivani Mathur ◽

Karl Kassier ◽

Janetta Rossouw ◽

Robert Wightman ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Preoperative Imaging ◽

Renal Neoplasm ◽

Renal Masses ◽

Cystic Renal Cell Carcinoma ◽

Eosinophilic Cytoplasm ◽

Clear Cell Rcc

Two sporadic cases of eosinophilic solid and cystic renal cell carcinoma (ESC RCC), at our institution, are presented in this study to contribute to the growing literature on this novel renal neoplasm. The first patient was a 38-year-old female with two synchronous renal masses measuring 3.5 and 1.9 cm on preoperative imaging. The second patient was a 44-year-old female with an incidental renal mass measuring 4 cm. Both patients underwent uncomplicated radical nephrectomies. The 1.9 cm mass in the first patient was consistent with clear cell RCC. The dominant mass in the first patient and the tumor in the second patient had microscopic and macroscopic findings in keeping with ESC RCC including a tan appearance, abundant eosinophilic cytoplasm, and CK20+ and CK7− staining. Both patients had an uncomplicated course following surgery with no evidence of local recurrence or distant metastatic disease for 1 and 2 years for the first and second patient accordingly. These cases contribute to a growing body of literature regarding ESC RCC including, to our knowledge, the first reported case of synchronous ESC RCC and clear cell RCC. Further research about this novel renal neoplasm is needed.

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

Scientific Reports ◽

10.1038/s41598-021-81922-0 ◽

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.

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Economic Evaluation of Axitinib for Second Line Treatment in Adult Patients with Advanced Renal Cell Carcinoma – the Portuguese Case

Value in Health ◽

10.1016/j.jval.2014.08.2304 ◽

2014 ◽

Vol 17 (7) ◽

pp. A639-A640

Author(s):

L.S. Miguel ◽

R. Luz

Keyword(s):

Renal Cell Carcinoma ◽

Economic Evaluation ◽

Cell Carcinoma ◽

Renal Cell ◽

Adult Patients ◽

Advanced Renal Cell Carcinoma ◽

Line Treatment ◽

Second Line

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Second-line cabozantinib versus nivolumab in advanced renal cell carcinoma: Systematic review and indirect treatment comparison

Critical Reviews in Oncology/Hematology ◽

10.1016/j.critrevonc.2018.10.004 ◽

2019 ◽

Vol 139 ◽

pp. 143-148 ◽

Cited By ~ 4

Author(s):

Camillo Porta ◽

Cezary Szczylik ◽

Roman Casciano ◽

Shuai Fu ◽

Billy Amzal ◽

...

Keyword(s):

Systematic Review ◽

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Advanced Renal Cell Carcinoma ◽

Second Line ◽

Indirect Treatment Comparison ◽

Treatment Comparison ◽

Indirect Treatment

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Clinical experience with everolimus in the second-line treatment of advanced renal cell carcinoma

Therapeutic Advances in Urology ◽

10.1177/1756287215591764 ◽

2015 ◽

Vol 7 (5) ◽

pp. 286-294 ◽

Cited By ~ 2

Author(s):

Daniele Alesini ◽

Claudia Mosillo ◽

Giuseppe Naso ◽

Enrico Cortesi ◽

Roberto Iacovelli

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Clinical Experience ◽

Renal Cell ◽

Advanced Renal Cell Carcinoma ◽

Line Treatment ◽

Second Line

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

International Journal of Surgical Pathology ◽

10.1177/1066896918763948 ◽

2018 ◽

Vol 26 (6) ◽

pp. 536-541 ◽

Cited By ~ 2

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.

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IMPA2 Downregulation Enhances mTORC1 Activity and Restrains Autophagy Initiation in Metastatic Clear Cell Renal Cell Carcinoma

Journal of Clinical Medicine ◽

10.3390/jcm9040956 ◽

2020 ◽

Vol 9 (4) ◽

pp. 956 ◽

Cited By ~ 1

Author(s):

Chia-Hao Kuei ◽

Hui-Yu Lin ◽

Hsun-Hua Lee ◽

Che-Hsuan Lin ◽

Jing-Quan Zheng ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Mtor Inhibitors ◽

Gene Set Enrichment Analysis ◽

Cellular Migration ◽

Cell Renal Cell Carcinoma ◽

Gene Set

Although mTOR inhibitors have been approved as first-line therapy for treating metastatic clear cell renal cell carcinoma (ccRCC), the lack of useful markers reduces their therapeutic effectiveness. The objective of this study was to estimate if inositol monophosphatase 2 (IMPA2) downregulation refers to a favorable outcome in metastatic ccRCC receiving mTOR inhibitor treatment. Gene set enrichment analysis predicted a significant activation of mTORC1 in the metastatic ccRCC with IMPA2 downregulation. Transcriptional profiling of IMPA2 and mTORC1-related gene set revealed significantly inverse correlation in ccRCC tissues. Whereas the enforced expression of exogenous IMPA2 inhibited the phosphorylation of Akt/mTORC1, artificially silencing IMPA2 led to increased phosphorylation of Akt/mTORC1 in ccRCC cells. The pharmaceutical inhibition of mTORC1 activity by rapamycin reinforced autophagy initiation but suppressed the cellular migration and lung metastatic abilities of IMPA2-silenced ccRCC cells. In contrast, blocking autophagosome formation with 3-methyladenine rescued the mitigated metastatic potential in vitro and in vivo in IMPA2-overexpressing ccRCC cells. Our findings indicated that IMPA2 downregulation negatively activates mTORC1 activity and could be a biomarker for guiding the use of mTOR inhibitors or autophagy inducers to combat metastatic ccRCC in the clinic.

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