scholarly journals Absolute quantitative proteomics using the total protein approach to identify novel clinical immunohistochemical markers in renal neoplasms

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Susana Jorge ◽  
José L. Capelo ◽  
William LaFramboise ◽  
Swati Satturwar ◽  
Dimitrios Korentzelos ◽  
...  

Abstract Background Renal neoplasms encompass a variety of malignant and benign tumors, including many with shared characteristics. The diagnosis of these renal neoplasms remains challenging with currently available tools. In this work, we demonstrate the total protein approach (TPA) based on high-resolution mass spectrometry (MS) as a tool to improve the accuracy of renal neoplasm diagnosis. Methods Frozen tissue biopsies of human renal tissues [clear cell renal cell carcinoma (n = 7), papillary renal cell carcinoma (n = 5), chromophobe renal cell carcinoma (n = 5), and renal oncocytoma (n = 5)] were collected for proteome analysis. Normal adjacent renal tissue (NAT, n = 5) was used as a control. Proteins were extracted and digested using trypsin, and the digested proteomes were analyzed by label-free high-resolution MS (nanoLC-ESI-HR-MS/MS). Quantitative analysis was performed by comparison between protein abundances of tumors and NAT specimens, and the label-free and standard-free TPA was used to obtain absolute protein concentrations. Results A total of 205 differentially expressed proteins with the potential to distinguish the renal neoplasms were found. Of these proteins, a TPA-based panel of 24, including known and new biomarkers, was selected as the best candidates to differentiate the neoplasms. As proof of concept, the diagnostic potential of PLIN2, TUBB3, LAMP1, and HK1 was validated using semi-quantitative immunohistochemistry with a total of 128 samples assessed on tissue micro-arrays. Conclusions We demonstrate the utility of combining high-resolution MS and the TPA as potential new diagnostic tool in the pathology of renal neoplasms. A similar TPA approach may be implemented in any cancer study with solid biopsies.

2021 ◽  
pp. 106689692199322
Author(s):  
Seyed Mohammad Mohaghegh Poor ◽  
Shivani Mathur ◽  
Karl Kassier ◽  
Janetta Rossouw ◽  
Robert Wightman ◽  
...  

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.


2015 ◽  
Vol 11 (6) ◽  
pp. 1708-1716 ◽  
Author(s):  
Francesca Raimondo ◽  
Samuele Corbetta ◽  
Andrea Savoia ◽  
Clizia Chinello ◽  
Marta Cazzaniga ◽  
...  

Set-up of a specific protocol for membrane protein analysis, applied to label free, comparative proteomics of renal cell carcinoma microdomains.


2014 ◽  
Vol 8 (11-12) ◽  
pp. 928 ◽  
Author(s):  
Cevahir Özer ◽  
Mehmet Resit Gören ◽  
Tulga Egilmez ◽  
Nebil Bal

Renal oncocytomas accounts for 3% to 9% of primary renal neoplasms. The coexistence of renal cell carcinoma (RCC) within the oncocytoma is extremely rare. We report the case of an asymptomatic 74-year-old man with papillary RCC within oncocytoma managed with left radical nephrectomy.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 357-357 ◽  
Author(s):  
Paul Russo ◽  
Robert G. Uzzo ◽  
William Thomas Lowrance ◽  
Aviva Asnis-Alibozek ◽  
Norman David LaFrance ◽  
...  

357 Background: Use of cross-sectional imaging has increased the detection rate for small renal tumors; more patients now present with early-stage renal cell carcinoma (RCC) or benign or indolent renal masses. Histopathology after surgical resection is the definitive method for characterizing renal tumors. Stage migration of renal masses creates uncertainty about the percentage of resected masses that will be benign vs malignant. We sought to better define these proportions through a targeted review of the literature. Methods: PubMed/select congresses were searched to identify the histologic classification of renal masses in a representative sample from the contemporary literature: [search] incidence AND (renal cell carcinoma AND benign); incidence AND (renal tumor AND benign); percentage AND (renal cell carcinoma AND benign); limit: 2003–2011. Results: Most representative studies included procedures conducted in the mid-1990s to the mid-to-late 2000s. Studies origin was US (n=8), Korea (n=3), China, Japan, Germany, Austria, Australia, and multisite (Israel/France/US; all n=1). Only 8 studies had n≥500 (range, 70–10,404). The proportion of benign masses are shown (see Table); half of the studies reported values between 16% and 17%. The majority found that benign tumors were more likely to be smaller in size (<4 or <7 cm) than malignant tumors. 11 studies reported the RCC subtype (% clear cell range, 46%–83%). Conclusions: Benign renal tumors occur ~15% of the time and are more prevalent among small masses. Nearly 25% of resected lesions are benign or indolent and may not require surgery. Preoperative discrimination of more aggressive renal masses would be an important clinical advance that could improve clinicians’ diagnostic confidence and guide patient management. Funding: Wilex AG/IBA Molecular. [Table: see text]


2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 622-622
Author(s):  
Adithya Balasubramanian ◽  
Weidong Zhou ◽  
Emanuel Petricoin ◽  
Charles F. Streckfus ◽  
John R Klein ◽  
...  

622 Background: We aimed to explore the salivary proteomic profile (SPP) of patients undergoing surgery for suspected renal cell carcinoma (RCC), then evaluate any significant findings in a validation cohort. Methods: Prospective IRB approved trial of consecutive patients with suspected RCC undergoing curative surgery. Saliva was collected pre- and postoperatively, and from healthy volunteers. Saliva was mixed with sodium orthovanadate and protease inhibitor, aliquoted, and frozen at -80oC. SPP performed using biomarker concentrated saliva via core-shell hydrogel nanoparticles functionalized with molecular baits coupled to high resolution MS/MS electrospray mass spectrometry analysis; output represented as spectral counts. Wilcoxon Rank Sum test was used for comparisons; p-values were adjusted using false discovery rate (FDR) for multiple testing. Results: Exploratory phase: saliva was collected from 27 volunteers and 34 RCC patients (24 clear cell (cc)RCC, 6 chromophobe (ch)RCC, 4 other). Evaluation of cc vs chRCC revealed differential counts for 56 proteins; none were significant after adjustment by FDR. Comparison of matched pre/post-operative SPP in 14 ccRCC patients identified differential counts of 3 proteins: basic salivary proline-rich protein 3 precursor; prolactin-inducible protein precursor; and submaxillary gland androgen-regulated protein 3B precursor. These were not affected by patient age, partial/radical nephrectomy, or tumor size/stage/grade. Validation phase: power analyses indicated a sample size of 38/53 patients = 90% power = effect size of 0.6/0.5, respectively, 2-sided Type 1 error of 0.025. 49 ccRCC patients were enrolled with pre/postop saliva. 611 proteins were identified; none had differential counts after FDR. Conclusions: Using a unique biomarker technology coupled to high resolution MS, interesting SPP’s were seen between RCC subtypes and before/after ccRCC curative resection. We were unable to show significant differences in pre/post-op levels. More research is needed to further study the SPP in RCC patients and the factors impacting their differential expression. In order to aid such efforts, the raw data will be made available for future researchers.


2020 ◽  
Author(s):  
Hyun Jung Lee ◽  
Dong Hoon Shin ◽  
Joon Young Park ◽  
So Young Kim ◽  
Chung Su Hwang ◽  
...  

Abstract Background: The presence of histologically different neoplasms in the same organ is rare in pathologic practice. We report the first case of synchronous clear cell renal cell carcinoma (clear cell RCC) and papillary renal neoplasm with reverse polarity (PRNRP) with comprehensive immunohistochemical and molecular characterization using next-generation sequencing (NGS). Case presentation: A 61-year-old man was incidentally found to have a left renal mass on imaging studies performed for workup of left back pain and urine color change for one week. A laparoscopic left radical nephrectomy was performed. Gross examination showed lobulated masses measuring 5.6 × 4.0 × 3.3 cm in the upper to mid pole and 1.1 × 1.0 × 1.0 cm in the lower pole. Microscopic findings revealed these to be two different separate masses of clear cell renal cell carcinoma and papillary renal neoplasm with reverse polarity. NGS analyses revealed KRAS gene mutation (c.35G>T/p.G12V in exon 2) in the papillary renal neoplasm with reverse polarity, with PIK3CA gene mutation restricted to the clear cell renal cell carcinoma (c.1624G>A/p.E542K in exon 10).Conclusions: We report here an extraordinarily rare case of synchronous renal tumors of papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma. We identified simultaneous KRAS and PIK3CA mutations in two different renal masses in the same kidney for the first time. New pathologic assessment with comparative molecular analysis of mutational profiles may be helpful for tumor studies.


Author(s):  
Saket Sarswat ◽  
Vimlesh . ◽  
D.P. Soni

Background: Kidney can be involved in various pathological process. Both benign & malignant tumors can occur in the kidney. They arise from different components of renal parenchyma, notably tubular epithelium.1 99 percent of renal neoplasms are malignant, with renal cell carcinoma and wilm’s tumor being the most common2. Men have higher incidence than women (approximately 1.6:1) and vast majority are diagnosed after 65 years of age. Material and methods: Prospective and retrospective study from January 2017 to December 2019 in the Department of Pathology. Results: The study comprised of 67 cases of neoplastic conditions, out of which 63 cases are malignant and only 4 cases were recorded as benign. Conclusion: Malignant tumors far more common than benign lesions. In adults and older individuals, renal cell carcinoma was most common while among paediatric age group, wilms tumor was most common. Benign tumors were uncommon. Keywords: Kidney, renal cell carcinoma, wilms tumor


2020 ◽  
pp. 1-3
Author(s):  
Richa Chauhan ◽  
Richa Chauhan ◽  
Gyanendra Singh ◽  
Upendra Prasad Singh

Renal cell carcinoma (RCC) is an uncommon malignant tumor of the kidney, particularly in the Asian population. It is more commonly seen in an elderly male patient with typical complains of haematuria, flank pain and lump. Recently incidental diagnosis of small RCCs has been rising due to increased used of abdominal imaging for other reasons. Spontaneous rupture of a renal mass leading to large perinephric collection and presenting as an acute pain abdomen in an adult male is a rare finding but should be considered as a differential diagnosis. The most common cause of spontaneously ruptured renal mass includes benign tumor as angiomyolipoma followed by malignant tumor like RCC, vascular causes, coagulation defects and infection in other cases. Contrast enhanced CT scan is the most common imaging modality used for diagnosis. Initial resuscitation depending up on the patient’s general condition followed by nephrectomy for malignant tumors and embolization for benign tumors is the treatment of choice.


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