Histogenesis of renal cell carcinoma and renal oncocytoma: An immunohistochemical study

Cohen, Cynthia; McCue, Peter A.; DeRose, Patricia B.

doi:10.1002/1097-0142(19881101)62:9<1946::aid-cncr2820620913>3.0.co;2-s

Cited by 63 publications

(31 citation statements)

References 37 publications

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“…Those observations led to the conclusion that TCC epithelial cells show aberrant renal tubular differentiation. This coexistence of proximal and distal tubules characteristics has been reported in several renal tumors [3,4,8,15] indicating that aberrant tubular differentiation may be a common occurrence in renal neoplasms regardless of their nephron origin. All reported cases present a homogeneous macroscopic and cytoarchitectural appearance: they have a spongy "bubble-wrap" appearance due to small to interme- diate (and occasionally large) cystic structures dispersed within a thin fibrotic stroma.…”

Section: Discussionsupporting

confidence: 70%

Tubulocystic carcinoma of the kidney: a new entity among renal tumors

et al. 2007

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Tubulocystic carcinoma is a tumor entity, which is not yet included in the WHO-classification of renal tumors. We report a series of 11 cases of this tumor, 6 of which were examined in by immunohistochemistry using a panel of five antibodies (CK7, CK34betaE12, CK19, CD10 and P504S). All patients were men. Each had renal tumor stage of pT1N0M0, with a diameter of 1.7 to 7 cm (mean, 3.3 cm). None of the patients presented with recurrence or metastases. Grossly, tumors were microcystic masses with a bubble-wrap appearance. Histological features included cysts and small tubules, separated by delicate septa and lined by flat to columnar or hobnail cells. The cyst and tubule epithelium showed immunohistochemical characteristics of both proximal and distal tubules. Tubulocystic carcinoma is a distinctive kidney tumor, with noteworthy macroscopic and microscopic characteristics, which can be distinguished from other cystic kidney tumors, including cystic nephroma, multilocular cystic renal cell carcinoma and some solid tumors with extensive cystic changes. More cases are needed to ascertain its prognosis. Tubulocystic carcinoma should be considered as a new subtype of renal cell carcinoma in the next revision of the WHO classification.

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Section: Discussionsupporting

confidence: 70%

Tubulocystic carcinoma of the kidney: a new entity among renal tumors

et al. 2007

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“…On the other hand, distal tubulus epithelial cells represent the precursor cells of oncocytomas. 16 Thus, PTEN expression is nearly lost during carcinogenesis of ccRCCs, suggesting an important role in tumorigenesis. In contrast, loss of PTEN during pathogenesis of oncocytomas was not observed, since PTEN expression is less intense in both oncocytomas and their precursor (distal tubulus) epithelial cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Loss of tumor suppressor protein PTEN during renal carcinogenesis

Brenner

Färber

Herget

et al. 2002

Intl Journal of Cancer

123

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The tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) encodes a dual specific protein and phospholipid phosphatase that affects cell proliferation, apoptosis and migration. In our study, we examined protein expression of PTEN in renal carcinogenesis. PTEN protein levels were examined in 42 clear cell renal cell carcinomas (ccRCC) and oncocytomas as well as in the corresponding normal renal tissue of the same patients using Western blot analysis. Cellular localization was analyzed by immunohistochemistry. PTEN was highly expressed in all investigated normal renal tissue specimens. Immunohistochemical analysis showed an almost exclusive staining of proximal tubulus epithelial cells known to be precursor cells of ccRCC. Within the proximal tubulus cells, PTEN exhibited a membrane predominant immunostaining pattern. In ccRCCs PTEN expression was markedly reduced to an average of less than 10% compared with normal tissue as evidenced by Western blot analysis (p < 0.001). The degree of reduction was similar in highly differentiated (G1) carcinomas and in less differentiated (G2-G4) carcinomas. Key words: PTEN; renal cell carcinoma; oncocytoma; proximal tubulus epithelial cellThe human tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) located on chromosome 10q23 1 encodes a dual specific protein and phospholipid phosphatase that is involved in regulation of a variety of signal transduction pathways. PTEN inhibits Shc (Src-homology collagen) phosphorylation following epidermal growth factor (EGF) stimulation and therefore blocks the activation of the Ras/MAPkinase pathway. This has been proposed as an explanation for the tumor suppressive effect of PTEN. 2 Another mechanism that involves the protein phosphatase activity of PTEN is dephosphorylation and inactivation of focal adhesion kinase (FAK), thus implying a crucial role of PTEN for the interaction between extracellular matrix and the cytoskeleton. This mechanism may lead to negative regulation of integrin mediated cell spreading, migration and invasion. 3,4 Besides its function as a protein phosphatase, PTEN acts as a phospholipid phosphatase with phosphatidylinositol 3,4,5-triphosphate (PIP3) as a substrate. [5][6][7] One of the direct downstream targets of PIP3, protein kinase B (Akt/PKB), is continually activated by phosphorylation in cells lacking functional PTEN and the elevated levels of activation can in turn be reduced to normal levels by expression of wild-type PTEN. 8 These data suggest that the tumor suppressive properties of PTEN relate in part to its ability to downregulate the Akt/PKB pathway and hence inhibit cell proliferation and facilitate apoptosis. PTEN is frequently deleted or mutated in advanced cancers, thus suggesting a crucial role in tumor development. Loss of PTEN has been implicated in the carcinogenesis in a wide variety of tissues including prostate, bladder, melanoma, breast and brain. 9,10 However, in renal cancer, PTEN has not yet been shown to play a rol...

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“…Although it is widely believed that VHL associated renal tumors originate from the proximal nephron [1,107], it has been shown that CC-RCCs can express markers of both, the distal and the proximal nephron [110][111][112][113], implying a multipotential capacity of neoplastic renal cells to synthesize antigens that can be associated with different tubular segments and different stages of nephrogenesis. More recently Maxwell's group reported that in kidneys from VHL patients "early" multicellular lesions appeared to be more frequently derived from Tamm-Horsfall protein (THP) expressing tubular segments than from the proximal tubule.…”

Section: Conditional Inactivation Of Pvhl In the Kidney: Towards The mentioning

confidence: 99%

The VHL tumor suppressor in development and disease: Functional studies in mice by conditional gene targeting

Haase

2005

Seminars in Cell & Developmental Biology

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The von Hippel-Lindau tumor suppressor pVHL plays a critical role in the pathogenesis of familial and sporadic clear cell carcinomas of the kidney and hemangioblastomas of the retina and central nervous system. pVHL targets the oxygen sensitive alpha subunit of hypoxia-inducible factor (HIF) for proteasomal degradation, thus providing a direct link between tumorigenesis and molecular pathways critical for cellular adaptation to hypoxia. Cell type specific gene targeting of VHL in mice has demonstrated that proper pVHL mediated HIF proteolysis is fundamentally important for survival, proliferation and differentiation of many cell types and furthermore, that inactivation of pVHL may, unexpectedly, inhibit tumor growth under certain conditions. Mouse knock out studies have provided novel mechanistic insights into VHL associated tumorigenesis and established a central role for HIF in the development of the VHL phenotype.

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Histogenesis of renal cell carcinoma and renal oncocytoma: An immunohistochemical study

Cited by 63 publications

References 37 publications

Tubulocystic carcinoma of the kidney: a new entity among renal tumors

Tubulocystic carcinoma of the kidney: a new entity among renal tumors

Loss of tumor suppressor protein PTEN during renal carcinogenesis

The VHL tumor suppressor in development and disease: Functional studies in mice by conditional gene targeting

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