The co-expression of CA9, HIF-1α, and GLUT-1 in the absence of VHL gene alterations in clear-cell papillary renal cell carcinoma suggests activation of the HIF pathway by non-VHL-dependent mechanisms.
The co-expression of CA9, HIF-1α, and GLUT-1 in the absence of VHL gene alterations in clear-cell papillary renal cell carcinoma suggests activation of the HIF pathway by non-VHL-dependent mechanisms.
Almost all CCPRCC-like tumors (82%) lacked the characteristic immunoprofile of sporadic CCPRCC (CK7, CAIX, CD10, AMACR), often showing diffuse CD10 labeling (64%), negative or focal CK7 reactivity (55%), or both (18%).
Almost all CCPRCC-like tumors (82%) lacked the characteristic immunoprofile of sporadic CCPRCC (CK7, CAIX, CD10, AMACR), often showing diffuse CD10 labeling (64%), negative or focal CK7 reactivity (55%), or both (18%).
Almost all CCPRCC-like tumors (82%) lacked the characteristic immunoprofile of sporadic CCPRCC (CK7, CAIX, CD10, AMACR), often showing diffuse CD10 labeling (64%), negative or focal CK7 reactivity (55%), or both (18%).
In conclusion, the coexpression of CA9 and HIF-1α in the absence of VHL gene abnormalities in CCPRCC suggests activation of the HIF pathway by mechanisms independent of VHL gene mutation.
In conclusion, the coexpression of CA9 and HIF-1α in the absence of VHL gene abnormalities in CCPRCC suggests activation of the HIF pathway by mechanisms independent of VHL gene mutation.
We analyzed 11 tumors from two distinct cohorts with TCEB1 mutations along with an expanded cohort to assess whether these should be considered an entity distinct from clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma.
The aim of our project was to investigate specific renal immunohistochemical biomarkers involved in the hypoxia-inducible factor pathway and mutations in the VHL gene to clarify the relationship between ccpRCC and RAT.
Diffuse labeling for CK7 can uncommonly be observed in clear cell renal cell carcinomas confirmed to have chromosome 3p loss, although these do not exhibit the expected staining pattern of clear cell papillary renal cell carcinoma, including positivity for CD10 and AMACR.
By immunohistochemistry, 7/9 (78%) of the clear cell cases were diffusely positive for both CK7 and CAIX resembling the pattern seen in clear cell papillary renal cell carcinoma.
Clear cell papillary renal cell carcinoma (CCPRCC) cases were evaluated for mutations on the following genes: KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR.
Clear cell papillary renal cell carcinoma (CCPRCC) cases were evaluated for mutations on the following genes: KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR.
We selected 14 cases of CCPRCC with a wide spectrum of morphological features diagnosed on morphology and CK7 immunoreactivity and analysed them using a panel of immunohistochemical markers, focusing on 34βE12 and related CKs 1,5,10 and 14 and several molecular analyses such as fluorescence in situ hybridisation (FISH), array comparative genomic hybridisation (aCGH), VHL methylation, VHL and TCEB1 sequencing and multiplex ligation-dependent probe amplification (MLPA).
We selected 14 cases of CCPRCC with a wide spectrum of morphological features diagnosed on morphology and CK7 immunoreactivity and analysed them using a panel of immunohistochemical markers, focusing on 34βE12 and related CKs 1,5,10 and 14 and several molecular analyses such as fluorescence in situ hybridisation (FISH), array comparative genomic hybridisation (aCGH), VHL methylation, VHL and TCEB1 sequencing and multiplex ligation-dependent probe amplification (MLPA).
We concluded that: (1) immunohistochemical expression of CK7 is necessary for diagnostic purposes, but may not be sufficient to identify CCPRCC, while 34βE12, in part due to the presence of CK14 antigen expression, can be extremely useful for the recognition of this tumour; and (2) further molecular analysis of chromosome 3p should be considered to support of CCPRCC diagnosis, when FISH analysis does not evidence the common loss of chromosome 3p.
Twenty-five cases were morphologically and immunophenotypically consistent with CCPRCC; all of them showed diffuse CK7 expression and cup-like reactivity with CAIX.