A distinct expression pattern and point mutation of c-kit in papillary renal cell carcinomas.

KIT is expressed not only in tumors derived from hematopoietic stem cells, melanocytes, germ cells, mast cells, and interstitial cells of Cajal, but also in other malignancies such as chromophobe renal cell carcinoma. This pattern of KIT expression prompted us to investigate the expression and mutation of c-kit gene exons 9, 11, 13, 17, and intron 17 in the different subtypes of renal cell carcinomas (n=66) and non-neoplastic kidneys (n=12). We found that KIT showed strong immunoreactivity in the cytoplasm of papillary renal cell carcinomas (100%), but on the cell membranes of chromophobe renal cell carcinomas (100%). Interestingly, a specific point mutation of the c-kit intron 17 (T->A) was found only in papillary renal cell carcinomas (94%). Our study demonstrates that the expression pattern and one mutation of c-kit may distinguish papillary renal cell carcinomas.     

C-kit expression in renal oncocytomas and chromophobe renal cell carcinomas

C- kit encodes the membrane-bound tyrosine kinase KIT, whose expression has been identified in several types of human neoplasms. Recently, KIT has been reported to be a marker for chromophobe renal cell carcinoma (RCC) and renal angiomyolipoma. However, expression of this molecule has not been adequately studied in other renal tumors, particularly oncocytoma, which may morphologically resemble chromophobe RCC. In this study, we analyzed c- kit messenger RNA (mRNA) levels in 17 chromophobe RCCs and 20 renal oncocytomas obtained from complementary DNA (cDNA) microarrays. Furthermore, comprehensive immunohistochemical analysis of KIT protein using a monoclonal antibody was performed in 226 renal tumors including chromophobe RCC (n=40), oncocytoma (n=41), clear-cell RCC (n=40), renal angiomyolipoma (n=29), and papillary RCC (n=21) on tissue microarrays (TMAs) and was compared with immunostaining results from 25 chromophobe RCCs and 30 oncocytomas using standard sections. The staining intensity was semiquantitatively graded on a 3-tier scoring system. All chromophobe RCCs and oncocytomas showed significant overexpression of c- kit mRNA. The average increase of mRNA compared with normal kidney tissue was 7.4-fold for chromophobe RCCs and 7.4-fold for oncocytomas. Immunohistochemical expression of KIT was found in most chromophobe RCCs (95% in TMAs and 96% in conventional sections) and oncocytomas (88% in TMAs and 100% in conventional sections) but was infrequently observed in renal angiomyolipomas (17%), papillary RCCs (5%), and clear-cell RCCs (3%). Furthermore, the average KIT immunoreactivity in TMAs was stronger in chromophobe RCC (1.93) and oncocytoma (2.07) than in other subtypes of renal tumors tested, including angiomyolipomas (0.17), papillary RCCs (0.05), and clear-cell RCCs (0.03). In conclusion, we found a significant elevation of c- kit mRNA by cDNA expression microarrays and overexpression of KIT protein by immunohistochemistry not only in chromophobe RCCs but also in oncocytomas. In contrast, immunohistochemical expression of KIT was not detected in most other types of renal cell tumors evaluated. The differential expression of c- kit in these renal tumors may have diagnostic and therapeutic implications.     

肾细胞癌中抑癌基因PTEN的表达及生物学意义

目的 :研究抑癌基因PTEN在肾细胞癌的表达及其生物学意义。方法 :应用免疫组织化学S P法检测 5例正常肾组织、18例癌旁肾组织和 40例肾细胞癌组织中抑癌基因PTEN的表达。结果 :5例正常肾组织和 18例癌旁肾组织均有较强的PTEN蛋白的表达 ,二者PTEN蛋白的表达强度、阳性细胞的分布形式无差异。抑癌基因PTEN在肾细胞癌中的表达不同于正常肾组织和癌旁肾组织 ,12 5 %的肾细胞癌呈PTEN蛋白阴性 ;17 5 %的肾细胞癌PTEN蛋白呈弱阳性 ;70 %的肾细胞癌PTEN蛋白呈阳性或强阳性 ,与癌旁组织PTEN蛋白的染色强度无差异。PTEN蛋白阴性的肾细胞癌 ,肾门淋巴结转移率为80 % ;PTEN蛋白阳性的肾细胞癌 ,肾门淋巴结转移率为 2 0 %。PTEN蛋白阴性肾细胞癌的肾门淋巴结转移率与PTEN阳性肾细胞癌的肾门淋巴结转移率比较 ,差异有显著性 (P <0 0 5 )。结论 :肾细胞癌中存在着抑癌基因PTEN的表达缺失和异常 ;抑癌基因PTEN的表达异常可能与肾细胞癌的发生、发展有关 ,抑癌基因PTEN是肾细胞癌的一种新的相关基因。     

Loss or reduction of Fhit expression in renal neoplasias: correlation with histogenic class

Involvement of the 3p14.2 region of chromosome 3 in kidney cancers was suggested 20 years ago, when a reciprocal constitutional translocation, t(3;8)(p14.2;q24), was shown to segregate with bilateral clear cell renal carcinoma in 3 generations of 1 family. The FHITgene that is interrupted at 3p14.2 by the t(3;8) translocation has been isolated, characterized, and shown to be frequently altered, mainly by internal deletion, in carcinomas or cancer-derived cell lines of the lung, stomach, pancreas, esophagus, cervix, and colon. Although up to 90% of sporadic clear cell renal carcinomas, representing 70% of adult renal carcinomas, exhibit loss of FHIT alleles, FHIT gene alterations have been documented for only a few renal cell carcinoma-derived cell lines. Nevertheless, more than 50% of clear cell carcinomas were recently shown to express little or no Fhit protein, unlike the normal kidney tubule epithelium, which is uniformly strongly positive for Fhit expression. We have extended our immunohistochemical study of expression of Fhit protein to the spectrum of histopathologic subtypes of adult renal tumors. There is an apparent continuum of Fhit expression from the 100% strongly positive oncocytomas through mostly positive papillary and chromophobe to the mostly negative clear cell and sarcomatoid to the negative or predominantly negative collecting duct renal carcinomas. This pattern of diminishing Fhit expression correlates with reported frequency of 3p allele loss in renal carcinomas and may parallel the potential for aggressive behavior of tumors, as suggested by the abundant Fhit expression in the benign oncocytomas and the near absence of Fhit expression in sarcomatoid and collecting duct RCCs.     

Claudin-7 and claudin-8: immunohistochemical markers for the differential diagnosis of chromophobe renal cell carcinoma and renal oncocytoma

Claudin-7 and claudin-8 code for tight junction proteins expressed in distal nephron epithelium. In a recent oligonucleotide microarray study, we identified claudin-7 and claudin-8 as candidate markers to distinguish chromophobe renal cell carcinoma from other renal tumors, including oncocytoma. Distinction of these lesions can be difficult by light microscopy but is clinically important because chromophobe renal cell carcinoma has malignant biological potential, whereas renal oncocytoma is benign. Claudin-7 and claudin-8 expression was studied by immunohistochemistry in 11 chromophobe renal cell carcinomas and 17 oncocytomas using formalin-fixed paraffin-embedded tissue sections of tumor with adjacent nonneoplastic kidney. Steam antigen retrieval was performed before immunohistochemistry. Specificity was verified by negative control reactions without primary antibody and appropriate membranous staining patterns in positive control tissues (colon carcinoma and adjacent nonneoplastic kidney). Claudin-7 protein was expressed in a membranous pattern in 10 of 11 chromophobe renal cell carcinomas and 4 of 17 oncocytomas (P < .01). Claudin-8 was expressed in multiple patterns: In oncocytoma, 11 of 17 cases showed cytoplasmic, 4 of 17 membranous, and 2 of 17 negative reactions. In chromophobe renal cell carcinoma, 0 of 11 cases showed cytoplasmic, 3 of 11 membranous, and 8 of 11 negative reactions (P < .01). The immunohistochemical pattern of membranous claudin-7 and negative claudin-8 was seen in 7 of 11 chromophobe renal cell carcinomas and 1 of 17 oncocytomas (63% sensitivity, 84% specificity, 88% positive predictive value for chromophobe renal cell carcinoma). Negative claudin-7 and cytoplasmic claudin-8 were observed in 10 of 17 oncocytomas and 0 of 11 chromophobe renal cell carcinomas (59% sensitivity, 100% specificity and positive predictive value for oncocytoma). The distal nephron proteins claudin-7 and claudin-8 have potential use as immunohistochemical biomarkers in the differential diagnosis of chromophobe renal cell carcinoma and oncocytoma. Expression of claudin-7 and claudin-8 may reflect the relationship of chromophobe renal cell carcinoma and oncocytoma to intercalated cells of the cortical collecting duct. It may be necessary to identify additional biomarkers to include with claudin-7 and claudin-8 in a larger immunohistochemical panel to improve diagnostic sensitivity and specificity.     

Different immunohistochemical patterns of Fhit protein expression in renal neoplasms.

BACKGROUND: The FHIT gene on human chromosome 3p14.2 is deleted in a variety of malignant tumors, including clear cell renal carcinomas (RCCs) resulting in a loss of expression of Fhit protein. The Fhit expression in specific subtypes of renal carcinomas has not been characterized. We have investigated the association of Fhit expression with particular subtypes of renal tumors to determine the role and specificity of this putative tumor suppressor gene in renal neoplasia. MATERIAL AND METHODS: The immunohistochemical expression of Fhit was tested in normal kidneys and in 109 renal neoplasms consisting of 51 clear cell RCCs, 26 papillary RCCs, two chromophobe carcinomas, six oncocytomas, four pelvic transitional cell carcinomas and 20 Wilms' tumors from formalin fixed and routinely processed tissue. RESULTS: Normal renal tubules expressed Fhit strongly and consistently. The majority (78%) of clear cell RCCs showed reduced or absent expression of Fhit, whereas the majority (74%) of papillary carcinomas, all chromophobe renal cell carcinomas, and oncocytomas were strongly positive. Sixty-eight percent of low-grade (G1 plus G2) but only 9% of high-grade (G3 plus G4) clear cell carcinomas were Fhit negative. Wilms' tumors demonstrated focal staining in the epithelial component in 8 of 20 cases (40%). CONCLUSIONS: The loss of Fhit expression in a high percentage of clear cell RCCs with conservation of Fhit in other types of tumors supports the proposed role of FHIT alterations in the genesis of clear cell carcinomas in contrast to other types of renal epithelial tumors. FHIT expression may play a role in epithelial differentiation of nephroblastomas (Wilms' tumors).     

Expression of intermediate filament proteins in subtypes of renal cell carcinomas and in renal oncocytomas. Distinction of two classes of renal cell tumors

We examined the expression of the diverse cytokeratin (CK) polypeptides as well as vimentin in human renal cell carcinomas of various subtypes and in renal oncocytomas by applying both two-dimensional gel electrophoresis and immunocytochemistry by using polypeptide-specific monoclonal antibodies. The tumors were classified according to the guidelines of the World Health Organization, with some modifications based primarily on recently proposed cytomorphological criteria. All clear cell carcinomas (G I, G II; N = 20) co-expressed CKs nos. 8 and 18, and vimentin, with CK no. 19 being present in 13 of the 20 cases and exhibiting a heterogeneous distribution. Dedifferentiated carcinomas (G III; N = 8) also co-expressed CKs nos. 8 and 18 as well as vimentin, but in addition, exhibited CK no. 19 and, in many cases, CK no. 7; in 1 case, only vimentin was expressed. Both eosinophilic-granular (N = 3) and basophilic (small cell cuboidal; N = 6) carcinomas contained CKs nos. 8 and 18, and the co-expression of vimentin was a consistent feature of these tumors; CK no. 19 was found in all of these cases, while CK no. 7 was present in the majority. In chromophobe cell carcinomas (N = 8), in contrast to all of the other carcinoma types, no vimentin was detected in the tumor cells, with only CKs nos. 8, 18, and to a variable extent 7, being present. Similarly, oncocytomas (N = 8) lacked vimentin and exhibited only CKs nos. 8 and 18. Conspicuous scattered CK no. 19-positive cells were found in these two last tumor types. No CK polypeptides other than simple-epithelium-type CKs (nos. 7, 8, 18, and 19) were detected in any of the tumors studied. These results indicate that, in renal cell tumors, the expression of intermediate-filament proteins is strikingly correlated with the specific morphologic appearance. While the co-expression of CKs nos. 8 and 18 and vimentin was a surprisingly consistent feature of the most common subtypes of renal cell carcinomas, CK no. 19 exhibited remarkable heterogeneity of expression both within individual tumors and between different tumors, the expression patterns of this CK being correlated to the tumor subtypes. The consistent absence of vimentin in chromophobe cell carcinomas and oncocytomas makes it possible to define these as a separate class of renal cell tumors. This finding supports the view that chromophobe cell carcinomas represent a distinct tumor entity and points to their close phenotypic relationship to benign oncocytomas as well as to normal renal tubules.     

Immunoexpression of SDHB,FH, and CK20 among eosinophilic renal tumors: A tissue microarray study

BackgroundDifferential diagnosis can be a challenge for eosinophilic subtypes of renal cell tumors due to their overlapping histomorphological and immunohistochemical features. We aimed to investigate the frequency of rare variants of renal cell carcinomas (RCCs) such as succinate dehydrogenase-deficient RCC (SDDRCC), hereditary leiomyomatosis and RCC (HLRCC)-associated RCC, and eosinophilic, solid, and cystic RCC (ESCRCC) in our population.Materials and methodsRenal tumors which could be considered in the eosinophilic tumor category were included: 91 conventional clear cell RCCs with eosinophilic cytoplasm, 72 papillary RCCs, 74 chromophobe RCCs, 88 oncocytomas, and 37 other rare subtypes. Using the tissue microarray method, succinate dehydrogenase B (SDHB), fumarate hydratase (FH), and cytokeratin 20 (CK20) antibodies were performed by immunohistochemistry. Immunohistochemistry was repeated on whole block sections for selected cases. The utility of these antibodies in the differential diagnosis was also investigated.ResultsLoss of SDHB expression was detected in three tumors, two of which showed typical morphology for SDDRCC. In additional two tumors, SDHB showed weak cytoplasmic expression without a mitochondrial pattern (possible-SDHB deficient). None of the tumors showed loss of FH expression. Heterogeneous reactions were observed with SDHB and FH antibodies. Only one ESCRCC was detected with diffuse CK20 positivity.ConclusionSDDRCCs, HLRCC-associated RCCs, and ESCRCCs are very rare tumors depending on the population. Possible weak staining and focal loss of SDHB and FH expression should be kept in mind and genetic testing must be included for equivocal results.     

Expression of GLUT1 in primary renal tumors: morphologic and biologic implications

This study aimed to assess whether glucose transporter 1 (GLUT1) is useful in prognostication or differential diagnosis of renal tumors. GLUT1 immunostain for 228 renal tumors showed a membranous or cytoplasmic pattern. The membranous pattern was seen in 86.2% of 145 clear cell renal cell carcinomas (RCCs) and 100% of 11 transitional cell carcinomas (TCCs) but in no oncocytomas, other subtypes of RCC, or sarcomatoid areas of RCCs. The cytoplasmic pattern was seen in 55.2% of 145 clear cell RCCs, 38% of papillary RCCs (11/29), 13% of chromophobe RCCs (2/16), 22% of oncocytomas (5/23), and 82% of TCCs (9/11). Western blot showed a markedly increased GLUT1 protein content in clear cell RCCs compared with a low level in papillary RCCs and normal kidney specimens. GLUT1 expression in clear cell RCC was not significantly correlated with patient survival, tumor grade, or tumor stage. GLUT1 may be a novel target for immunotherapy and a useful marker in the differential diagnosis and classification of renal tumors.     

Ghrelin expression in normal kidney tissue and renal carcinomas

Ghrelin expression in cancers is either reduced/absent or increased depending on the organs involved. The aims of this study were to investigate: (i) whether there are differences in ghrelin peptide expression between kidney tissues from a series of renal cell carcinoma cases, oncocytomas, and normal controls; (ii) whether there are correlations between tissue ghrelin levels in a series of renal carcinoma cases and normal controls; and (iii) how normal is kidney ghrelin expression per mg tissue as compared with the normal stomach tissue ghrelin level. We studied 7 normal stomach and 7 normal kidney samples, 21 clear cell renal carcinomas, 7 chromophobe type renal cell carcinomas (RCC), 7 papillary type RCC, and 7 oncocytoma samples. Tissue ghrelin expression was measured by RIA and immunohistochemistry. Grades 1–3 clear renal cell carcinomas, chromophobe type RCC, papillary type RCC, and oncocytomas expressed 88%, 94%, 95%, 51%, 75%, and 48% less ghrelin than the normal kidney, respectively. Overall, we concluded that ghrelin expression in renal cell carcinoma tissues is always lower than that in normal kidney or is absent. This low level or lack of ghrelin may play a role in the etiopathogenesis and progression of cancer.     

Strong expression of chemokine receptor CXCR4 by renal cell carcinoma cells correlates with metastasis

The chemokine receptor CXCR4 is involved in the metastasis of many cancers. Recent evidence suggests that CXCR4 may be also involved in the metastasis of renal cell carcinoma. We analyzed the expression of CXCR4 in primary carcinomas, metastatic tissues and normal tissues using immunohistochemistry. We further investigated the migration of renal carcinoma cells in response to stimulation by CXCL12 in vitro. We also studied the subcellular localization of CXCR4 in renal cell carcinoma cells in response to CXCL12 by confocal microscopy. We observed the highest percentage of CXCR4 expression in renal cell carcinoma metastases compared with that in renal cell carcinomas and normal renal tissues. We further found that CXCR4 was localized predominantly in the membrane in primary renal cell carcinomas and predominantly in the cytoplasm in renal cell carcinoma metastases. Moreover, we found that CXCR4 was translocated from the cytoplasmic membrane to the cytoplasm upon stimulation by its ligand CXCL12. Renal cell carcinoma metastasis was associated with higher expression of CXCR4 and interaction of CXCR4 and its ligand CXCL12 resulted in the internalization of CXCR4 from the cytoplasmic membrane. These findings implicate the CXCR4-CXCL12 axis in the metastasis of renal cell carcinoma.     

Quantitative image cell analysis of cytologic smears for DNA ploidy in renal parenchymal neoplasms.

Quantitative image cell analysis for DNA ploidy was performed on cytologic smears from a series of 19 histologically proven cases of renal parenchymal tumors. These cases included chromophobe-cell carcinoma (n = 5), oncocytoma (n = 5), papillary carcinoma (n = 2), and conventional renal-cell carcinoma (n = 7). All chromophobe renal-cell carcinomas were composed predominantly of hypodiploid cells, while the five oncocytomas were virtually entirely composed of diploid cells. The papillary and conventional renal-cell carcinomas, on the other hand, showed a variety of ploidy profiles. Scatterplots generated by plotting nuclear DNA mass against nuclear area produced patterns that correlated with the morphologic type of the neoplasms. These findings indicate that quantitative image cell analysis for DNA ploidy may provide valuable clues that could be helpful in arriving at a precise diagnosis of renal parenchymal tumors. Diagn. Cytopathol. 1999;21:223-229.     

Cytokeratins 7 and 20 immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas.

Chromophobe renal cell carcinomas and renal oncocytomas share morphologic similarities and may present a diagnostic challenge on routine hematoxylin-eosin staining. Currently recommended additional studies of Hale's colloidal iron staining and electron microscopy are often difficult to interpret and technically challenging and may not be readily available. Previous studies have reported conflicting results with regard to the cytokeratin 7 staining pattern in chromophobe renal cell carcinomas and renal oncocytomas. Cytokeratin 20 expression in chromophobe renal cell carcinomas has not previously been studied. Formalin-fixed paraffin-embedded tissue of 11 chromophobe renal cell carcinomas and 21 renal oncocytomas were retrieved from the archived files (1984-2000) of four teaching hospitals. Of the 11 chromophobe renal cell carcinomas, eight stained positive (73%) for cytokeratin 7, one stained focally positive (9%), and two cases (18%) were completely negative. Cytokeratin 7 staining of the 21 oncocytomas revealed 4 positive (19%), 7 focally positive (33%), and 10 negative cases (48%). Cytokeratin 20 was uniformly negative on all 11 cases of chromophobe renal cell carcinomas and all 21 cases of oncocytomas. Cytokeratin 7 does not appear to show the consistent immunoreactivity in chromophobe renal cell carcinomas and renal oncocytomas, as has been previously suggested. Cytokeratin 20 immunostaining in chromophobe renal cell carcinomas and renal oncocytomas is uniformly negative. Despite the technical and interpretive challenges of Hale's colloidal iron, it is still the most useful stain in differentiating chromophobe renal cell carcinomas from renal oncocytomas.     

Cytokeratin 14 immunoreactivity distinguishes oncocytic tumour from its renal mimics: an immunohistochemical study of 63 cases

AIMS: The cytokeratin 14 (CK14) expression in oncocytomas or oncocytic tumours of various tissue origins has not been established. We have studied CK14 expression in 30 cases of oncocytic tumours of various tissue origins and 33 cases of renal cell carcinoma with overlapping features (mimics) by immunohistochemistry. METHODS AND RESULTS: Immunohistochemistry (ABC-HRP method) was performed for detection of CK14 in 30 cases of oncocytic tumour and 33 cases of renal mimics. To demonstrate CK14 specificity and sensitivity in oncocytic tumours, mES-13 (an anti-mitochondrial monoclonal antibody) immunohistochemistry was also performed in 20 of 30 cases on oncocytic tumour and all 33 cases of renal mimics. We found that all 30 cases of oncocytic tumour showed cytoplasmic CK14 positivity. All 20 cases of oncocytic tumour studied with mES-13 were positive. CK14 immunoreactivity was identified in only four cases of renal cell carcinoma (one conventional renal cell carcinoma with granular cytoplasm and three chromophobe renal cell carcinomas with eosinophilic cytoplasm). In contrast, all 33 cases of renal cell carcinoma were positive for mES-13 to varying degrees. CONCLUSION: The homogeneous, cytoplasmic, and granular CK14 immunoreactivity is sensitive and specific for oncocytic tumours, whereas CK14 immunoreactivity in renal mimics is light and sporadic with peripheral accentuation.     

Nucleophosmin expression in renal cell carcinoma and oncocytoma

The objective of this study was to investigate nucleophosmin/B23 (NPM) expression in renal cell carcinomas (RCC) and renal oncocytomas. The expression of NPM was studied by immunohistochemical methods on 59 RCCs, 9 oncocytomas, and 19 tumour-negative renal tissues. The expression was assessed relative to various clinicopathological variables and histological subtypes, to determine its potential role as a prognostic and diagnostic marker. All tumours showed nuclear staining, and a minority also exhibited cytoplasmic immunoreactivity. Two patterns of nuclear staining were observed: nuclear staining with a prominent nucleolus (nucleolar staining) and nuclear staining without a prominent nucleolus. There were significant differences, in both nuclear staining and cytoplasmic NPM expression, between oncocytomas and chromophobe RCCs (p < 0.001) and clear cell RCCs (p < 0.001). Cytoplasmic NPM expression was markedly lower in RCCs than in oncocytomas. A statistically significant correlation was discovered between nucleolar staining and nuclear grade (p < 0.001, r = 0.5). No relationship was found between cytoplasmic expression of NPM and any of the clinicopathological parameters or survival. NPM might be a useful immunohistochemical marker for differential diagnosis between oncocytoma and chromophobe RCC. In addition, increased nucleolar NPM expression in RCCs appears to be associated with tumour progression.     

Expression of secretagogin in clear-cell renal cell carcinomas is associated with a high metastasis rate

Renal cell carcinomas are divided into several subgroups according to their histopathologic characteristics. The outcome, therapy responses, and the applicability of molecular-targeted therapies depend on the tumor classification and on the tumor stage. Recent advances within the biomarker research facilitated the exact classification of the molecular character of the renal tumor. For example, the calcium-binding proteins parvalbumin and S-100A1 are characteristically expressed in renal cell carcinoma subgroups. This led us to investigate the expression of the novel calcium-binding protein secretagogin in renal cell carcinomas. Tissue microarray cylinders including 94 clear-cell renal cell carcinomas, 61 non-clear-cell renal cell carcinomas (37 papillary renal cell and 24 chromophobe carcinomas), and 30 oncocytomas were analyzed by immunohistochemistry. This showed remarkable secretagogin expression in 37% of the clear-cell renal cell carcinomas. Non-clear-cell renal cell carcinomas and oncocytomas were completely negative. Consequently performed immunoblotting analyses confirmed this expression profile. Because publicly available data direct toward a formation of a hierarchical cluster of secretagogin overexpressing clear-cell renal cell carcinomas, we conducted a clinical follow-up of the patients with clear-cell renal cell carcinoma. This revealed significantly more metastasis within the secretagogin-positive clear-cell renal cell carcinoma subgroup (49% versus 28%; P < .05). In conclusion, we report on detection of the novel calcium-binding protein secretagogin within a subgroup of clear-cell renal cell carcinomas. The increased metastasis rates within the secretagogin-positive subgroup of clear-cell renal cell carcinomas direct toward a clinical impact of our findings.     

Expression of bcl-2 oncoprotein in renal cell tumours

Expression of bcl-2 is associated with inhibition of apoptosis and extension of cell survival. The importance of apoptosis in relation to the development and progression of renal cell neoplasia remains undefined so far. In order to determine the expression of bcl-2 oncoprotein in normal and neoplastic renal cells, 37 renal tumours were investigated by immunolabelling, including 13 clear cell carcinomas, ten tubulopapillary carcinomas, four chromophobic renal cell carcinomas, and ten oncocytomas. Twenty-six samples of adjacent normal renal tissue served as controls. bcl-2 expression was correlated with cell proliferation activity as estimated by Ki67 antigen expression, and p53 protein expression in the tumour samples. The results demonstrate that in the normal kidney, positive bcl-2 immunostaining was present in glomerular parietal epithelial cells, in distal tubular cells, and in sparse proximal tubule cells. Renal cell tumours showed heterogeneous bcl-2 expression according to the tumour cell type. While the majority of carcinomas of clear cell type were usually negative or contained sparsely distributed positive cells, all tubulopapillary carcinomas were consistently positive for bcl-2. In oncocytomas and chromophobic carcinomas, there was a low percentage of bcl-2 immunoreactive tumour cells; some nuclear bcl-2 positivity was detected in one chromophobic tumour. These findings indicate variable bcl-2 oncoprotein expression in different types of renal cell tumours, with the highest level of expression in tubulopapillary carcinomas. No clear relationship was found between nuclear grade, cell proliferation activity, and level of bcl-2 expression. p53 protein was detected in only one tubulopapillary carcinoma.