Integrated transcriptional‐phenotypic analysis captures systemic immunomodulation following antiangiogenic therapy in renal cell carcinoma patients

The metastasis of chromophobe renal cell carcinoma to head and neck region, described herein, has never been reported before to our knowledge. A 56-year-old woman with a history of nephrectomy, that revealed chromophobe renal cell carcinoma six years before, presented left cervical mass. Imaging showed with left cervical lymphadenopathies and thyroid nodule. Surgery with histopathological examination confirmed that it was a left central and lateral jugular lymph node metastasis of chromophobe renal cell carcinoma treated postoperatively by antiangiogenic therapy. The patient was successfully treated by surgery and antiangiogenic drugs with stabilization and no recurrence of the metastatic disease. The case and the literature reported here support that chromophobe renal cell carcinoma can metastasize to the head and neck region and should preferentially be treated with surgery and antiangiogenic therapy because of the associated morbidity and quality-of-life issues.

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Abstract B10: ER stress protein GRP78 as a therapeutic target combined with antiangiogenic therapy in renal cell carcinoma

10.1158/1535-7163.pms-b10 ◽

2013 ◽

Author(s):

Kyung Seok Han ◽

Na Li ◽

Estelle Li ◽

Fazli Ladan ◽

Gleave Martin ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Er Stress ◽

Cell Carcinoma ◽

Therapeutic Target ◽

Renal Cell ◽

Antiangiogenic Therapy ◽

Stress Protein

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Abstract 945: PBRM1 loss reduces IFNγ-STAT1 activity and promotes resistance to immunotherapy and antiangiogenic therapy in renal cell carcinoma

10.1158/1538-7445.am2019-945 ◽

2019 ◽

Author(s):

Xiande Liu ◽

Wen Kong ◽

Christine Peterson ◽

Anh Hoang ◽

Xuesong Zhang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Antiangiogenic Therapy

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The level of FSHR expression in the primary kidney tumors to predict the response to subsequent antiangiogenic therapy with sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e21138 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e21138-e21138

Author(s):

Muhammad Ahsan Siraj ◽

Christophe Pichon ◽

Aurelian Radu ◽

Nicolae Ghinea

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Sensitivity And Specificity ◽

Renal Cell ◽

Kinase Inhibitor ◽

Antiangiogenic Therapy ◽

Total Density ◽

Kidney Tumors ◽

Cell Renal Cell Carcinoma ◽

Primary Tumors

e21138 Background: Sunitinib is an antiangiogenic receptor tyrosine kinase inhibitor used to treat advanced metastatic renal cell carcinoma and other types of cancer. Sunitinib is effective in only approx. 70% of clear cell renal cell carcinoma (CCRCC) patients, has significant adverse side effects, and no method is available to predict which patients will not respond. Our purpose was to explore the possibility of introducing an effective prediction method based on a marker of the tumor vasculature, the Follicle Stimulating Hormone Receptor (FSHR). Methods: Using immunohistochemistry on paraffin sections with anti-FSHR monoclonal antibodies we studied by photonic and fluorescence microscopy the expression of FSHR in 50 patients diagnosed with advanced metastatic CCRCC. All patients were subjected to surgery for removal of the primary tumor and were subsequently treated with sunitinib orally for ≥ 3 months with a dose of 50 mg/day for 4 weeks followed by 2 weeks off. After therapy the patients were categorized as “responsive”, “stable”, or “non-responsive” based on the RECIST guidelines. The blood vessel density and the percentage of FSHR-positive vessels were determined by immunofluorescence on sections from the primary tumors removed by surgery, prior to the sunitinib treatment. Von Willebrand factor (vWF) was used as specific endothelial marker. Results: There were no significant differences in the total density of vessels (detected with anti-vWF antibody) among the responsive, stable and non-responsive patients. The percentage of FSHR-stained vessels was on average five fold higher for the patients that responded to the treatment in comparison with the stable group and almost eight fold higher than in the non-responsive group. The percentage allowed the detection of responders with 87-100% sensitivity and specificity. Conclusions: The data suggest that FSHR expression levels in the blood vessels of CCRCC primary tumors can be used to predict, with high sensitivity and specificity, the patients that will respond to sunitinib therapy.

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STAT-3 and Β-catenin expression in metastatic clear cell renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.583 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 583-583

Author(s):

Aline Fusco Fares ◽

Isabela Cunha ◽

Daniel Vilarim Araujo ◽

Leonardo de Azevedo Boente ◽

Daniel Garcia ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Systemic Therapy ◽

Renal Cell ◽

Clear Cell ◽

Antiangiogenic Therapy ◽

Prognostic Scores ◽

Cancer Center ◽

Cell Renal Cell Carcinoma ◽

Prognostic Criteria

583 Background: In mRCC, there are no prospectively validated biomarkers to guide the treatment and therapy decision is based on prognostic scores and histology. STAT-3 and Wnt/b-cateninare cell proliferation pathways and have already been related to prognostic in renal cell carcinoma. Objective: to evaluate the role of STAT-3 and b-catenin expression as prognostic biomarkers in clear cell mRCC. Methods: 684 medical records of renal cell carcinoma patients treated at AC Camargo Cancer Center from 2007 to 2015 were reviewed. 86 out of 684 patients fulfilled the study criteria: metastatic clear cell carcinoma, no sarcomatoid features, previous systemic therapy, previous nephrectomy and available tumor specimens from metastatic site. Pathological samples were arranged in a TMA. The number of positive stainings cells for each antibody in each core was categorized as low positive or negative versus highly positive expression. Results: We had available tissue blocks from 47 tumors. 32/45 patients (71,1%) had highly positive membrane b-catenin and none of the patients was positive for nuclear b-catenin. 27 /45 (60%) were categorized as low positive or negative STAT-3. There was no statistically significant association between STAT-3 and b-catenin expression with clinical prognostic criteria (MSKCC and Heng criteria). In the multivariate analysis, KPS < 80% (p = 0.02; HR: 2.7), time from nephrectomy to metastasis < 1 year (p = 0.04; HR: 2.1), no hypothyroidism (p = 0.05; HR: 2.4) and MSKCC criteria (p = 0.02; HR: 2.5) were confirmed as negative prognostic factors. Associative analysis showed that none of the patients with negative membrane b-catenin had response to systemic therapy (p=0.02). OS was 35.5 months (IC 22.2-48.8) and PFS was 12.5 months (IC 10.0-14.0). Conclusions: in our cohort, STAT-3 and B-catenin expression are not associated with the prognostic criteria (MSKCC and Heng). The loss of B-catenin expression is associated to a worse response rate to antiangiogenic therapy in metastatic clear cell renal cancer. [Table: see text]

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