Reactivity of <scp>CK</scp>7 across the spectrum of renal cell carcinomas with clear cells

Gonzalez, Manuel Lora; Alaghehbandan, Reza; Pivovarcikova, Krystina; Michalová, Květoslava; Rogala, Joanna; Martínek, Petr; Foix, Maria Pane; Condom, Enric; Compérat, Éva; Ulamec, Monika; Hora, Milan; Michal, Michal; Hes, Ondřej

doi:10.1111/his.13791

Cited by 18 publications

(10 citation statements)

References 21 publications

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“…In addition, both chromophobe RCC and clear cell papillary RCC are typically positive for CK7, while conventional ccRCC is usually not, which grants it pivotal importance in the differential diagnosis among clear cell renal neoplasms (36). In 2018, Gonzalez et al suggested that CK7 immunoreactivity in ccRCC is variable and the extent of staining depends on the clinical-histopathological parameters including grade and architectural growth patterns of the tumors (37). Ki-67 is a marker of cellular proliferation and is also involved in ribosomal RNA transcription (38).…”

Section: Discussionmentioning

confidence: 99%

An Integrated Score and Nomogram Combining Clinical and Immunohistochemistry Factors to Predict High ISUP Grade Clear Cell Renal Cell Carcinoma

et al. 2018

Front. Oncol.

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Objective: The International Society of Urological Pathology (ISUP) has proposed a grading system to classify renal cell carcinoma (RCC). However, classification using biopsy specimens remains problematic and, consequently, the accuracy of a biopsy-based diagnosis is relatively poor. This study aims to combine clinical and immunohistochemical (IHC) factors for the prediction of high ISUP grade clear cell RCC (ccRCC) in an attempt to complement and improve the accuracy of a biopsy-based diagnosis.Methods: A total of 362 ccRCC patients were enrolled in this study and used for the training set. We performed IHC analysis of 18 protein markers on standard tissue sections using an automated stainer. Multivariate logistic regression models were developed to evaluate independent predictors for high ISUP grade. We evaluated different prediction models using receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) analysis. A nomogram for the derivation of an integrated score for predicting high ISUP grade ccRCC and a calibration curve were also plotted. Finally, an internal validation cohort was examined to evaluate the performance of our integrated scoring system and nomogram.Results: Multivariate logistic analyses revealed seven credible candidates for predicting high grade ISUP. These were age, tumor diameter, surgery, and CK7, Ki-67, PTEN, and MTOR protein expression. The ROC curves for the clinical, IHC and integrated models were compared in the training set, and the AUC for each was 0.731, 0.744, and 0.801, respectively. DeLong's test showed that the integrated model was significantly better at predicting high ISUP grade, when compared with the other models. Internal validation confirmed the good performance of the integrated score in predicting ISUP grade.Conclusion: We have developed a nomogram integrating clinical and immunohistochemical parameters to predict high ISUP grade for M0 ccRCC patients. This nomogram may offer potentially useful information during preoperative individualized patient risk assessment, and consequently may help urologists when planning personalized management regimens.

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Section: Discussionmentioning

confidence: 99%

An Integrated Score and Nomogram Combining Clinical and Immunohistochemistry Factors to Predict High ISUP Grade Clear Cell Renal Cell Carcinoma

et al. 2018

Front. Oncol.

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“…Among the three types of tissues, the expression of KRT7 was lower in ccRCC cancer tissues and the least in thrombus tissues. An IHC study showed that the extent of KRT7 staining depended on the grade of ccRCC, those with the low-grade ccRCC expressed significantly higher levels of KRT7 than those of the high-grade ones [ 28 ]. This suggests that low KRT7 expression might correlate with a more malignant biological behavior.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis reveals distinctive protein expression patterns of thrombus in clear cell renal cell carcinoma

Zhou

Song

Xing

et al. 2021

Translational Oncology

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Clear cell renal cell carcinoma (ccRCC) is a type of malignant tumor of the urinary system. The renal vein or vena cava thrombus can be found in a subset of ccRCC patients in whom it leads to worse prognosis. However, the protein expression profile and molecular features of ccRCC thrombus remain largely unclear. Here, a comparative proteomic analysis was performed using the 2D-LC-MS strategy for the thrombus-tumor-normal tissue triples of 15 ccRCC patients. Statistical analysis, GO enrichment analysis, protein-protein interaction network construction, and mRNA-based survival analysis were used to interpret the proteomic data. Three dysregulated proteins, GGT5 (gamma-glutamyl transferase 5), KRT7 (keratin 7) and CFHR1 (complement factor H related 1), were analyzed using western blot (WB) and immunohistochemistry (IHC) to validate the reliability of the proteomic analysis. The result of this analysis revealed 251 dysregulated proteins, which could be divided into 11 clusters depending on the changing trends, among the thrombus, tumor, and normal tissues. Several pathways and regulation networks were found to be associated with the thrombus, and some dysregulated proteins showed potential values for prognosis prediction. WB and IHC results were in accordance with the proteomic results, further validating the reliability of this study. In conclusion, our findings provide an overview of the thrombus at the molecular level as well as valuable information for further pathological studies or research on biomarkers and therapeutic targets.

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“…Conversely, a few studies claim that VHL variants may not distinguish ccpRCC from ccRCC. For example, a study of 15 tumors found that they are morphologically identical to ccpRCC and that most express CK7; however, molecular profiling indicates that a subgroup of these tumors carries VHL abnormalities [26]. Thus, this group is defined as "clear cell papillary-like RCC" [26].…”

Section: Discussionmentioning

confidence: 99%

“…For example, a study of 15 tumors found that they are morphologically identical to ccpRCC and that most express CK7; however, molecular profiling indicates that a subgroup of these tumors carries VHL abnormalities [26]. Thus, this group is defined as "clear cell papillary-like RCC" [26]. Due to the rarity of this kind of renal carcinoma, previous studies did not find variants in common.…”

Section: Discussionmentioning

confidence: 99%

Clear Cell Papillary Renal Cell Carcinoma Shares Distinct Molecular Characteristics and may be Significantly Associated With Higher Risk of Developing Second Primary Malignancy

Tian

et al. 2021

Pathol. Oncol. Res.

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Traditionally, clear cell papillary renal cell carcinoma (ccpRCC) was considered to share similar molecular and histological characteristics with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Here we aimed to identify somatic and germline variants of ccpRCC. For this purpose, we conducted whole-exome sequencing to detect somatic variants in the tissues of 18 patients with pathologically confirmed ccpRCC, who underwent surgical treatment at Fudan University Shanghai Cancer Center. Targeted sequencing was conducted to detect germline variants in paired tumor or normal tissues or blood. Somatic and germline variants of ccRCC and Renal cell carcinoma included in The Cancer Genome Atlas data and other published data were analyzed as well. The molecular profiles of ccpRCC, ccRCC and pRCC were compared. Among the 387 somatic variants identified, TCEB1 (3/18) and VHL (3/18) variants occurred at the highest frequencies. Germline mutation detection showed that nine variants associated with Fanconi anemia (VAFAs) pathway (FANCA, 6/18; FANCI, 3/18) were identified in 18 ccpRCC patients. Among ccpRCC patients with VAFAs, five out of eight patients had second primary malignancy or family history of cancer. Somatic variants characteristics may distinguish ccpRCC from ccRCC or pRCC and germline VAFAs may be a molecular characterization of ccpRCC. Compared with ccRCC or pRCC, ccpRCC patients may be significantly correlated with higher risk of developing second primary malignancy.

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Reactivity of CK7 across the spectrum of renal cell carcinomas with clear cells

Cited by 18 publications

References 21 publications

An Integrated Score and Nomogram Combining Clinical and Immunohistochemistry Factors to Predict High ISUP Grade Clear Cell Renal Cell Carcinoma

An Integrated Score and Nomogram Combining Clinical and Immunohistochemistry Factors to Predict High ISUP Grade Clear Cell Renal Cell Carcinoma

Proteomic analysis reveals distinctive protein expression patterns of thrombus in clear cell renal cell carcinoma

Clear Cell Papillary Renal Cell Carcinoma Shares Distinct Molecular Characteristics and may be Significantly Associated With Higher Risk of Developing Second Primary Malignancy

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