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.

Expression of Galectin-3 in Renal Neoplasms: A Diagnostic, Possible Prognostic Marker

2010 ◽  
Vol 134 (1) ◽  
pp. 90-94
Author(s):  
Jane Y. Dancer ◽  
Luan D. Truong ◽  
Qihui Zhai ◽  
Steven S. Shen
Keyword(s):  
Renal Cell ◽  
Clear Cell ◽  
Strong Association ◽  
Prognostic Significance ◽  
Low Grade ◽  
Renal Neoplasms ◽  
Galectin 3 ◽  
Lectin Family ◽  
Clear Cell Rccs ◽  
Clear Cell Rcc

Abstract Context. Galectin-3, a member of the lectin family, was shown to be expressed in normal distal tubular cells and in renal cell carcinomas (RCC). However, its diagnostic and prognostic significance in RCC is as yet undefined. Objectives. To describe the expression of Galectin-3 among different histologic subtypes of renal neoplasms and to determine their diagnostic and prognostic significances. Design. The expression of Galectin-3 was evaluated in 217 renal neoplasms by tissue microarray and immunohistochemistry with semiquantitative analysis. Results. Strong expression of Galectin-3 was observed in 92 of 217 of renal neoplasms (42.4%). Although 22 of 23 oncocytomas (95.7%) and 19 of 21 chromophobe RCCs (90.5%) express Galectin-3, only 4 of 32 papillary RCCs (12.5%) and 47 of 137 clear cell RCCs (34.3%) express Galectin-3, suggesting that it may be used as a potential diagnostic marker. Galectin-3 expression was seen in 55% of high-grade (Fuhrman nuclear grades 3 and 4) versus 21% low-grade (grades 1 and 2) clear cell RCCs (P < .001). Conclusions. This study confirms that Galactin-3 is strongly overexpressed in renal cell neoplasms of distal tubular differentiation, that is, oncocytoma and chromophobe RCCs, suggesting it might be used as a possible differential diagnostic tool for renal cell neoplasm with oncocytic or granular cells. Furthermore, we observed a strong association of overexpression of Galectin-3 and high nuclear grade in clear cell RCC. These results also suggest a possible pivotal role for Galectin-3 in the differentiation and prognosis of clear cell RCC.

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.

scholarly journals Clear Cell Carcinomas of the Mullerian System: Does the Pathogenesis Vary Depending on Their Nuclear Grade and Their Association with Endometriosis? An Immunohistochemical Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ahmad Alduaij ◽  
Katrine Hansen ◽  
Tahreem A. Karim ◽  
Cunxian Zhang ◽  
Michelle M. Lomme ◽  
...  
Keyword(s):  
Clear Cell ◽  
Immunohistochemical Analysis ◽  
Nuclear Grade ◽  
High Grade ◽  
Ki 67 ◽  
High Nuclear Grade ◽  
Positive Immunostaining

Clear cell carcinomas (CCC) of the mullerian system are considered high grade tumors, but morphologically, the cells of CCC show both low and high grade features. The aims of the current study were to categorize CCC into low and high nuclear grade types, correlate their association with endometriosis, and then observe possible variations in pathogenesis based on their expression of p53 and Ki-67. We studied 41 pure mullerian CCCs and designated each as either a high (HNG) or low (LNG) nuclear grade tumor. Morphologically, 17 (41%) CCCs were LNG and 24 (59%) were HNG. Nine (38%) HNG and 2 (12%) LNG tumors showed positive immunostaining with p53. Endometriosis was associated with 8 (47%) LNG tumors and 8 (33%) HNG CCCs. Of the 11 cases with p53 alteration, 4 (1 LNG and 3 HNG) were associated with endometriosis. Conclusions: HNG CCCs, irrespective of their association with endometriosis, have alterations of p53. In general, LNG ovarian and endometrial CCCs, irrespective of their association with endometriosis/adenomyosis, are less likely to show p53 alteration. It appears that mullerian CCCs may have variable pathogenesis depending on their nuclear grade and association with endometriosis. A larger study is needed to validate these findings.

The Diagnostic Accuracy of Percutaneous Renal Needle Core Biopsy and Its Potential Impact on the Clinical Management of Renal Cortical Neoplasms

2014 ◽  
Vol 138 (12) ◽  
pp. 1673-1679 ◽  
Author(s):  
Lan L. Gellert ◽  
Rohit Mehra ◽  
Ying-Bei Chen ◽  
Anuradha Gopalan ◽  
Samson W. Fine ◽  
...  
Keyword(s):  
Clinical Management ◽  
Renal Cell ◽  
Core Biopsy ◽  
Clear Cell ◽  
Renal Tumors ◽  
Low Grade ◽  
Renal Cell Carcinomas ◽  
Biopsy Diagnosis ◽  
Potential Impact ◽  
Renal Cortical Neoplasms

Context While biopsies are now increasingly being performed for the diagnosis of renal cortical neoplasms, the influence of the rendered pathological diagnoses on the clinical management is only rarely documented. Objectives To report our experience with consecutively performed renal biopsies and the potential impact of the diagnosis on subsequent clinical management. Design Material from needle biopsies performed consecutively at our institution between 2006 and 2011 was reviewed. The influence of the reported pathology results on the clinical management was determined from patient follow-up medical record review. Results In total, 218 percutaneous biopsies for renal masses were performed during this period. Among them, 181 (83%) yielded neoplastic tissue, including 81 clear cell renal cell carcinomas, 29 low-grade oncocytic neoplasms, 7 papillary renal cell carcinomas, 5 clear cell papillary renal cell carcinomas, 5 angiomyolipomas, and 14 urothelial carcinomas. Fourteen additional cases (6%) contained lesional material from clinically known nonneoplastic processes, for a total diagnostic yield of 89%. Twenty-three (11%) were nonrepresentative of lesional tissue. In 10 of these, repeat biopsies or resections established the diagnosis of renal tumors. Biopsy diagnosis was confirmed in 29 of 30 cases (97%) on subsequent nephrectomy. Following the biopsy diagnosis, there were significant differences in the clinical management; overall, 79% of clear cell renal cell carcinomas received therapeutic interventions, and 17% were put on active surveillance. In contrast, 77% of the benign or low-grade lesions were put on active surveillance. Conclusions Accurate and specific diagnosis can be rendered on renal core biopsy in most renal tumors, and the biopsy diagnosis can have a definitive role in their clinical management.

Oncocytic Biliary Cystadenocarcinoma: A Case Report and Review of the Literature

2004 ◽  
Vol 128 (2) ◽  
pp. e25-e28 ◽  
Author(s):  
Richard L. Bardin ◽  
Jacqueline K. Trupiano ◽  
Russell M. Howerton ◽  
Kim R. Geisinger
Keyword(s):  
Prognostic Significance ◽  
Cytokeratin 20 ◽  
Cytoplasmic Staining ◽  
Female Patients ◽  
Biliary Cystadenocarcinoma ◽  
Granular Cytoplasm ◽  
Mesenchymal Stroma ◽  
The Right ◽  
Papillary Neoplasm ◽  
Granular Cytoplasmic Staining

Abstract We report an unusual case of biliary cystadenocarcinoma with oncocytic differentiation. The patient was a 43-year-old woman who presented with right upper quadrant pain. Imaging revealed a 16 × 10 × 10-cm, heterogenous, right hepatic mass with extension into the right atrium. Surgical resection revealed a papillary neoplasm of malignant cells with atypical hyperchromatic nuclei and prominent nucleoli lining fibrovascular cores. Mesenchymal stroma was not present. The majority of the epithelial cells had abundant eosinophilic granular cytoplasm, consistent with oncocytic differentiation. There was extensive stromal and hepatic parenchymal invasion. Immunohistochemical staining revealed a “biliary pattern” of cytokeratin subset immunoreactivity, with positivity for cytokeratin 7 and an absence of staining with cytokeratin 20. The tumor was negative for mucin, carcinoembryonic antigen, α-fetoprotein, calretinin, CD31, and chromogranin. There was granular cytoplasmic staining with phosphotungstic acid hematoxylin, consistent with the presence of abundant mitochondria. Electron microscopy revealed abundant mitochondria within the neoplastic cells. This case is quite unusual because female patients only rarely lack the characteristic ovarian-like mesenchymal stroma of biliary cystadenomas/cystadenocarcinomas. Furthermore, to our knowledge, oncocytic differentiation in this neoplasm has been reported previously on only 2 occasions. The biologic behavior and prognostic significance, if any, of the lack of mesenchymal stroma in female patients or the presence of oncocytic differentiation remains to be further elucidated as more of these cases are described.

Claudin-7 Immunohistochemistry in Renal Tumors: A Candidate Marker for Chromophobe Renal Cell Carcinoma Identified by Gene Expression Profiling

2007 ◽  
Vol 131 (10) ◽  
pp. 1541-1546 ◽  
Author(s):  
Christopher D. Hornsby ◽  
Cynthia Cohen ◽  
Mahul B. Amin ◽  
Maria M. Picken ◽  
Diane Lawson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Clear Cell ◽  
Renal Tumor ◽  
Renal Tumors ◽  
Tumor Subtypes ◽  
Chromophobe Rcc ◽  
Clear Cell Rccs ◽  
Expression Marker

Abstract Context.—The differential diagnosis of eosinophilic renal tumors can be difficult by light microscopy. In particular, chromophobe renal cell carcinoma (RCC) is difficult to distinguish from oncocytoma. This differential diagnosis is important because chromophobe RCC is malignant, whereas oncocytoma is benign. Furthermore, chromophobe RCC has distinct malignant potential and prognosis compared with eosinophilic variants of other RCC subtypes. Immunohistochemistry is useful for distinguishing chromophobe RCC from other subtypes of renal carcinoma, but no expression marker reliably separates chromophobe RCC from oncocytoma. Objective.—In a previous gene expression microarray analysis of renal tumor subtypes, we found the distal nephron markers claudin-7 and claudin-8 to be overexpressed in chromophobe RCC versus oncocytoma and other tumor subtypes. We have confirmed similar findings in independent microarray data and validated differential claudin-7 protein expression by immunohistochemistry. Design.—Immunohistochemical analysis of claudin-7 in 36 chromophobe RCCs, 43 oncocytomas, 42 clear cell RCCs, and 29 papillary RCCs. Results.—Membranous claudin-7 expression was detected in 67% chromophobe RCCs, compared with 0% clear cell RCCs, 28% papillary RCCs, and 26% oncocytomas (P < .001). Conclusions.—Based on microarray and immunohistochemical data, we propose claudin-7 to be a candidate expression marker for distinguishing chromophobe RCC from other renal tumor subtypes, including the morphologically similar oncocytoma. The clinical utility of claudin-7 should be validated in independent studies of renal tumors, possibly in combination with additional targets in a multiplex immunohistochemical panel.

scholarly journals A Comparison of Death Domain-Associated Protein 6 in Different Endometrial Carcinomas Histotypes

2019 ◽  
Vol 14 ◽  
pp. 117727191986489
Author(s):  
Cao Jin ◽  
Sean Hacking ◽  
Miglena K Komforti ◽  
Mansoor Nasim
Keyword(s):  
Clear Cell ◽  
Point Mutations ◽  
Low Grade ◽  
Nuclear Staining ◽  
High Grade ◽  
Death Domain ◽  
Gynecology And Obstetrics ◽  
Grade 3 ◽  
Histologic Types ◽  
Endometrial Carcinomas

Background: Death domain-associated protein 6 (DAXX) is involved in regulating apoptosis via subcellular localization. The presence of DAXX point mutations correlates well with loss of nuclear expression on immunohistochemistry (IHC). In this study, we sought to determine (1) whether DAXX expression pattern is the same across different uterine carcinoma subtypes, and (2) which uterine carcinomas show loss of nuclear DAXX IHC. Design: We studied 65 uterine carcinomas of the following histologic types: 30 endometrioid (12 FIGO [The International Federation of Gynecology and Obstetrics] grade 1, 12 FIGO grade 2, and 6 FIGO grade 3), 8 serous, 14 clear cell, and 13 undifferentiated/dedifferentiated type (UEC/DDEC). Nuclear DAXX IHC was assessed in each tumor and was graded semi-quantitatively as follows: 0% to 50%, 50% to 75%, and greater than 75% of lesional cells react. Results: A total of 61% (25/41) of high-grade carcinomas (FIGO grade 3, serous, clear cell, and UEC/DDEC]) showed retained DAXX nuclear staining in >75% of lesional cells, compared with only 4.2% (1/24) of the low-grade carcinomas (FIGO grades 1 and 2) ( P = .0001), where DAXX expression was cytoplasmic. In addition, in the 11 DDEC cases, all the differentiated components showed loss of nuclear DAXX compared with the undifferentiated components which retained nuclear DAXX expression. Conclusions: We demonstrate that loss of nuclear DAXX is present in low-grade endometrial carcinomas and the differentiated components in UEC/DDEC, but not in high-grade ones, suggesting DAXX’s role in tumor progression and its potential as a therapeutic target in high-grade endometrial carcinomas.

Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

2015 ◽  
Vol 25 (7) ◽  
pp. 1201-1207 ◽  
Author(s):  
Esther Louise Moss ◽  
Tim Evans ◽  
Philippa Pearmain ◽  
Sarah Askew ◽  
Kavita Singh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clear Cell ◽  
Stage Iii ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Type I ◽  
High Grade ◽  
Type Ii ◽  
Ovarian Serous Carcinoma ◽  
Significant Difference

IntroductionThe dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium.MethodsAll cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers.ResultsOvarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases,P= 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III,P= 0.3758; stage IV,P= 0.4820).ConclusionsType II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.

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.

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