25 results on '"Bonetti, F."'
Search Results
2. Angiomyolipoma of the kidney: from simple hamartoma to complex tumour.
- Author
-
Caliò A, Brunelli M, Segala D, Zamboni G, Bonetti F, Pea M, and Martignoni G
- Subjects
- Angiomyolipoma diagnosis, Diagnosis, Differential, Hamartoma diagnosis, Humans, Kidney Neoplasms diagnosis, Perivascular Epithelioid Cell Neoplasms diagnosis, Perivascular Epithelioid Cell Neoplasms pathology, Angiomyolipoma pathology, Hamartoma pathology, Kidney Neoplasms pathology
- Abstract
Angiomyolipoma is the most common mesenchymal tumour of the kidney, even if for a long time it has been viewed as a hamartoma rather than a neoplasm. It belongs to a family of neoplasms, named PEComa, characterised by the constant presence of perivascular epithelioid cells that co-express smooth muscle and melanogenesis markers. Angiomyolipoma can occur in patients with tuberous sclerosis, a hereditary syndrome due to the alteration of TSC1 or TSC2 genes, or sporadically. Angiomyolipoma and its variants are indolent tumours; however, some epithelioid angiomyolipomas/pure epithelioid PEComas are aggressive, and criteria for malignancy have been proposed to identify those cases. Although typical angiomyolipoma is a straightforward diagnosis, pathologists should be aware of the wide morphological spectrum of its variants which could be tricky in routine clinical practice and could require immunohistochemical analysis for resolution. The differential diagnosis may range from an inflammatory process (for instance xanthogranulomatous pyelonephritis) to the most common renal cancers and sarcomas. The immunoexpression of melanogenesis markers (HMB45 and Melan-A) and cathepsin K is extremely helpful in the majority of cases. Recently, a subset of epithelioid angiomyolipoma/pure epithelioid PEComa harbouring TFE3 gene fusions has been described, raising questions about its relationship with the family of perivascular epithelioid cell tumour. The activation of the mTOR pathway due to genetic alterations of tuberous sclerosis complex in TSC1 or TSC2 genes in angiomyolipoma has also been reported as well as the subsequent therapeutic implications., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
3. PEComas of the kidney and of the genitourinary tract.
- Author
-
Martignoni G, Pea M, Zampini C, Brunelli M, Segala D, Zamboni G, and Bonetti F
- Subjects
- Humans, Kidney Neoplasms pathology, Perivascular Epithelioid Cell Neoplasms pathology, Urogenital Neoplasms pathology
- Abstract
PEComas are mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells that are characterized by the coexpression of muscle and melanogenetic markers. This group of lesions includes angiomyolipoma, clear cell "sugar" tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear cell tumors of other anatomical sites. In the genitourinary tract, PEComas have been described in the kidney, bladder, prostate, testis, and urethra. Although most PEComas behave as benign tumors, some are potentially malignant, and criteria for malignancy have been suggested for both and renal and extrarenal lesions. Recently, the expression of cathepsin K has been demonstrated in a large number of PEComas and has been proposed as a relatively specific marker to distinguish these proliferations from the majority of human cancers. In addition, a distinctive subset of PEComas harboring TFE3 gene fusions has been reported, giving rise to a possible relationship between them and MiTF/TFE family translocation renal cell carcinomas. The genetic alterations of tuberous sclerosis complex that promote activation of the mTOR pathway have been identified in PEComas. Therapy with mTORC1 inhibitors has been shown to be effective in some cases., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
4. Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney.
- Author
-
Martignoni G, Bonetti F, Chilosi M, Brunelli M, Segala D, Amin MB, Argani P, Eble JN, Gobbo S, and Pea M
- Subjects
- Adenoma, Oxyphilic enzymology, Angiomyolipoma enzymology, Case-Control Studies, Humans, Immunohistochemistry, Italy, Kidney Neoplasms pathology, Lymphangioleiomyomatosis enzymology, Perivascular Epithelioid Cell Neoplasms pathology, Biomarkers, Tumor analysis, Cathepsin K analysis, Kidney Neoplasms enzymology, Perivascular Epithelioid Cell Neoplasms enzymology
- Abstract
The perivascular epithelioid cell (PEC) is a unique cell type coexpressing contractile proteins (mainly α-smooth muscle actin), melanocytic markers, including microphthalmia-associated transcription factor (MITF), and estrogen and progesterone receptors. It is constantly present in a group of tumors called PEComas. Renal PEComas include the common angiomyolipoma as well as less common lesions such as microscopic angiomyolipoma, intraglomerular lesions, angiomyolipoma with epithelial cysts, epithelioid angiomyolipoma, oncocytoma-like angiomyolipoma and lymphangioleiomyomatosis of the renal sinus. It has been demonstrated that most of these lesions are determined by mutations affecting genes of the tuberous sclerosis complex, tuberous sclerosis 1 (TSC1) and tuberous sclerosis 2 (TSC2), with eventual deregulation of the RHEB/MTOR/RPS6KB2 pathway, and it has been observed that some PEComas regressed during sirolimus therapy, an MTOR inhibitor. Recently, overexpression of MITF has been related to the expression of the papain-like cysteine protease cathepsin K in osteoclasts where it has inhibited MTOR. The aim of this study is to evaluate cathepsin K immunohistochemically in the entire spectrum of PEComa lesions in the kidney. The study population consisted of 84 renal PEComa lesions, including 5 composed predominantly of fat (lipoma-like angiomyolipoma), 15 almost exclusively composed of spindle-shaped smooth muscle cells (leiomyoma-like angiomyolipoma) and 31 common angiomyolipomas composed of a mixture of fat, spindle and epithelioid smooth muscle cells, and abnormal thick-walled blood vessels, 15 microscopic angiomyolipomas, 5 intraglomerular lesions, 2 oncocytoma-like angiomyolipomas, 8 epithelioid angiomyolipomas, 2 angiomyolipomas with epithelial cysts and 1 example of lymphangioleiomyomatosis of the renal sinus. In all of the renal PEComas, cathepsin K was found to be constantly and strongly expressed and seems to be a more powerful marker than other commonly used markers for their identification, especially to confirm the diagnosis on needle biopsies.
- Published
- 2012
- Full Text
- View/download PDF
5. Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions.
- Author
-
Martignoni G, Gobbo S, Camparo P, Brunelli M, Munari E, Segala D, Pea M, Bonetti F, Illei PB, Netto GJ, Ladanyi M, Chilosi M, and Argani P
- Subjects
- Adolescent, Adult, Aged, Carcinoma, Renal Cell pathology, Cell Cycle Proteins genetics, Child, Chromosomes, Human, Pair 11, Chromosomes, Human, X, Female, Humans, Immunohistochemistry, Intracellular Signaling Peptides and Proteins, Kidney Neoplasms pathology, Male, Middle Aged, Neoplasm Proteins genetics, Oncogene Proteins, Fusion genetics, Sarcoma, Alveolar Soft Part pathology, Translocation, Genetic, Young Adult, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Carcinoma, Renal Cell enzymology, Carcinoma, Renal Cell genetics, Cathepsin K analysis, Gene Fusion, Kidney Neoplasms enzymology, Kidney Neoplasms genetics, Sarcoma, Alveolar Soft Part enzymology, Sarcoma, Alveolar Soft Part genetics
- Abstract
Cathepsin K is a protease whose expression is driven by microphthalmia transcription factor (MITF) in osteoclasts. TFE3 and TFEB are members of the same transcription factor subfamily as MITF and all three have overlapping transcriptional targets. We have shown that all t(6;11) renal cell carcinomas, which harbor an Alpha-TFEB gene fusion, as well as a subset of the Xp11 translocation renal carcinomas, which harbor various TFE3 gene fusions, express cathepsin K, while no other common renal carcinoma does. We have hypothesized that overexpression of TFEB or certain TFE3 fusion proteins function like MITF in these neoplasms, and thus activate cathepsin K expression. However, the expression of cathepsin K in specific genetic subtypes of Xp11 translocation carcinomas, as well as alveolar soft part sarcoma, which harbors the same ASPSCR1-TFE3 gene fusion as some Xp11 translocation carcinomas, has not been addressed. We performed immunohistochemistry for cathepsin K on 14 genetically confirmed t(X;1)(p11;q21) carcinomas, harboring the PRCC-TFE3 gene fusion; eight genetically confirmed t(X;17)(p11;q25) carcinomas, harboring the ASPSCR1-TFE3 gene fusion; and 18 alveolar soft part sarcomas (12 genetically confirmed), harboring the identical ASPSCR1-TFE3 gene fusion. All 18 alveolar soft part sarcomas expressed cathepsin K. In contrast, all eight ASPSCR1-TFE3 carcinomas were completely negative for cathepsin K. However, 12 of 14 PRCC-TFE3 carcinomas expressed cathepsin K. Expression of cathepsin K distinguishes alveolar soft part sarcoma from the ASPSCR1-TFE3 carcinoma, harboring the same gene fusion. The latter can be useful diagnostically, especially when alveolar soft part sarcoma presents in an unusual site (such as bone) or with clear cell morphology, which raises the differential diagnosis of metastatic ASPSCR1-TFE3 renal cell carcinoma. The difference in expression of cathepsin K between the PRCC-TFE3 and ASPSCR1-TFE3 carcinomas, together with the observed clinical differences between these subtypes of Xp11 translocation carcinomas, suggests the possibility of functional differences between these two related fusion proteins.
- Published
- 2011
- Full Text
- View/download PDF
6. Pure epithelioid PEComas (so-called epithelioid angiomyolipoma) of the kidney: A clinicopathologic study of 41 cases: detailed assessment of morphology and risk stratification.
- Author
-
Nese N, Martignoni G, Fletcher CD, Gupta R, Pan CC, Kim H, Ro JY, Hwang IS, Sato K, Bonetti F, Pea M, Amin MB, Hes O, Svec A, Kida M, Vankalakunti M, Berel D, Rogatko A, Gown AM, and Amin MB
- Subjects
- Adolescent, Adult, Aged, Angiomyolipoma epidemiology, Comorbidity, Female, Humans, International Cooperation, Kidney Neoplasms epidemiology, Logistic Models, Lymphatic Metastasis, Male, Middle Aged, Necrosis, Neoplasm Recurrence, Local pathology, Neoplasms, Multiple Primary pathology, Prognosis, Survival Rate, Tuberous Sclerosis epidemiology, Tuberous Sclerosis pathology, Young Adult, Angiomyolipoma pathology, Kidney Neoplasms pathology
- Abstract
Epithelioid angiomyolipomas (perivascular epithelioid cell tumors) of the kidney are defined as potentially malignant mesenchymal lesions that are closely related to classic angiomyolipoma. Although approximately 120 cases are published, mostly as case reports with variably used diagnostic criteria, the pathologic prognostic predictors of outcome are unknown. We analyzed the clinicopathologic parameters in a large series of 41 cases of pure epithelioid angiomyolipomas of the kidney, which we designate as pure (monotypic) epithelioid PEComas to contrast them from classic angiomyolipomas that are regarded by some as PEComas. We use the terminology "pure" to separate these cases from those that may have variable epithelioid components. The mean age of the patients was 40.7 years (range, 14 to 68 y). The male-to-female ratio was 1:1. Seventy-nine percent of patients were symptomatic at presentation with metastatic disease at onset in 12 cases. Follow-up and/or disease progression information were available for 33 of 41 cases (mean, 44.5 mo and median, 24.5 mo; range, 4 to 240); 9 patients had a history of associated tuberous sclerosis. Recurrence and metastasis were seen in 17% and 49% of patients; 33% of patients died of disease. Lymph node involvement was seen in 24% of patients; the liver (63%), lung (25%), and mesentery (18.8%) were the most common metastatic sites. Clinicopathologic parameters associated with disease progression (recurrence, metastasis, or death due to disease) in univariate analysis included associated tuberous sclerosis complex or concurrent angiomyolipoma (any metastasis, P=0.046), necrosis (metastasis at diagnosis, P=0.012), tumor size >7 cm (progression, P=0.021), extrarenal extension and/or renal vein involvement (progression, P=0.023), and carcinoma-like growth pattern (progression, P=0.040) (the 5 adverse prognostic parameters for pure epithelioid PEComas). Tumors with <2 adverse prognostic parameters (13 cases) were considered to be low risk for progression tumor, with 15% having disease progression. Tumors with 2 to 3 adverse prognostic parameters (14 cases) were considered to be "intermediate risk," with 64% having disease progression. Tumors with more than 4 or more adverse prognostic parameters (6 cases) were considered to be high risk, with all patients having disease progression. Of tumors with 3 or more adverse prognostic parameters, 80% had disease progression. An exact logistic regression analytic model showed that only carcinoma-like growth pattern and extrarenal extension and/or renal vein involvement were significant predictors of outcome (P=0.009 and 0.033, respectively). Our data of a large series with uniform definitional criteria confirm the malignant potential for pure epithelioid PEComas and provide adverse prognostic parameters for risk stratification in these patients.
- Published
- 2011
- Full Text
- View/download PDF
7. Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas.
- Author
-
Martignoni G, Pea M, Gobbo S, Brunelli M, Bonetti F, Segala D, Pan CC, Netto G, Doglioni C, Hes O, Argani P, and Chilosi M
- Subjects
- Adolescent, Adult, Aged, Carcinoma, Renal Cell metabolism, Cathepsin K, Child, Child, Preschool, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Kidney Neoplasms metabolism, Middle Aged, Oncogene Proteins, Fusion genetics, Oncogene Proteins, Fusion metabolism, Tissue Array Analysis, Translocation, Genetic, Young Adult, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Biomarkers, Tumor analysis, Carcinoma, Renal Cell genetics, Cathepsins biosynthesis, Kidney Neoplasms genetics
- Abstract
The microphthalmia transcription factor/transcription factor E (TFE)-family translocation renal cell carcinomas bear specific translocations that result in overexpression of TFE3 or TFEB. TFE3 fusion gene product overexpression occurs as consequence of different translocations involving chromosome Xp11.2, whereas TFEB overexpression is the result of the specific translocation t(6;11)(p21;q12), which fuses the Alpha gene to TFEB. Both TFE3 and TFEB are closely related members of the microphthalmia transcription factor/TFE-family, which also includes TFEC and microphthalmia transcription factor. These transcription factors have overlapping transcriptional targets. Overexpression of microphthalmia transcription factor has been shown to mediate the expression of cathepsin-K in osteoclasts. We hypothesize that the overexpression of the related TFE3 fusion proteins and TFEB in translocation renal cell carcinomas may have the same effect. We studied cathepsin-K in 17 cytogenetically confirmed microphthalmia transcription factor/TFE-family translocation renal cell carcinomas. Seven cases showed a t(6;11)(p21;q12), ten cases showed translocations involving Xp11.2; five cases t(X;1)(p11;q21) resulting in a PRCC-TFE3 gene fusion; three cases t(X;1)(p11;p34) resulting in a PSF-TFE3 gene fusion, one t(X;17)(p11;q25) resulting in an ASPL-TFE3 gene fusion, and one t(X;3)(p11;q23) with an unknown TFE3 gene fusion. As control we analyzed cathepsin-K in 210 clear cell, 40 papillary, 25 chromophobe renal cell carcinomas and 30 oncocytomas. All seven TFEB translocation renal cell carcinomas were labeled for cathepsin-K. Among the cytogenetically confirmed TFE3 translocation renal cell carcinomas, 6 out of 10 were positive. None of the other renal neoplasms expressed cathepsin-K. We conclude the following: (1) cathepsin-K is consistently and strongly expressed in TFEB translocation renal cell carcinomas and in 6 of 10 TFE3 translocation renal cell carcinomas. (2) Cathepsin-K immunolabeling in both TFE3 and TFEB translocation renal cell carcinomas distinguishes these neoplasms from the more common adult renal cell carcinomas, and may be a specific marker of these neoplasms. (3) These results further support the concept that the overexpression of TFE3 or TFEB in these neoplasms activates the expression of genes normally regulated by microphthalmia transcription factor in other cell types.
- Published
- 2009
- Full Text
- View/download PDF
8. Loss of chromosome 9p is an independent prognostic factor in patients with clear cell renal cell carcinoma.
- Author
-
Brunelli M, Eccher A, Gobbo S, Ficarra V, Novara G, Cossu-Rocca P, Bonetti F, Menestrina F, Cheng L, Eble JN, and Martignoni G
- Subjects
- Aged, Carcinoma, Renal Cell mortality, Carcinoma, Renal Cell pathology, Carcinoma, Renal Cell therapy, Female, Humans, Kaplan-Meier Estimate, Kidney Neoplasms mortality, Kidney Neoplasms pathology, Kidney Neoplasms therapy, Male, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Prognosis, Time Factors, Treatment Outcome, Carcinoma, Renal Cell genetics, Chromosome Deletion, Chromosomes, Human, Pair 9, Gene Expression Regulation, Neoplastic, In Situ Hybridization, Fluorescence, Kidney Neoplasms genetics
- Abstract
Loss of chromosome 9p has been implicated in the progression of renal cell carcinoma. We evaluated the clinical utility of fluorescence in situ hybridization analysis of loss of chromosome 9p in 73 patients with clear cell renal cell carcinomas with varied stage, size, grade, necrosis (SSIGN) scores. Loss of chromosome 9p was observed in 13 tumors (18%). The 5-year cancer-specific survival of patients without loss of chromosome 9p was 88% and was 43% in those with loss of chromosome 9p (P<0.001). Local extension of the primary tumor according to the 2002 TNM staging system, lymph node involvement, the presence of distant metastases, and the SSIGN score were the other variables that predicted cancer-specific survival in univariate analysis. Loss of chromosome 9p was an independent prognostic factor in multivariate analysis. Our data indicate that the detection of chromosome 9p loss by fluorescence in situ hybridization analysis of clear cell renal cell carcinoma adds prognostic information beyond the pathological factors included in the current predictive models for renal cell carcinoma, such as SSIGN score.
- Published
- 2008
- Full Text
- View/download PDF
9. Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study.
- Author
-
Rocca PC, Brunelli M, Gobbo S, Eccher A, Bragantini E, Mina MM, Ficarra V, Zattoni F, Zamò A, Pea M, Scarpa A, Chilosi M, Menestrina F, Bonetti F, Eble JN, and Martignoni G
- Subjects
- Adenoma, Oxyphilic diagnosis, Adenoma, Oxyphilic genetics, Adenoma, Oxyphilic metabolism, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell metabolism, Diagnosis, Differential, Humans, Immunohistochemistry, Kidney chemistry, Kidney metabolism, Kidney pathology, Kidney Neoplasms genetics, Kidney Neoplasms metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, S100 Proteins metabolism, Sensitivity and Specificity, Carcinoma, Renal Cell diagnosis, Kidney Neoplasms diagnosis, S100 Proteins genetics
- Abstract
S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.
- Published
- 2007
- Full Text
- View/download PDF
10. Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma.
- Author
-
Brunelli M, Gobbo S, Cossu-Rocca P, Cheng L, Hes O, Delahunt B, Pea M, Bonetti F, Mina MM, Ficarra V, Chilosi M, Eble JN, Menestrina F, and Martignoni G
- Subjects
- Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell pathology, Chromosome Aberrations, Kidney Neoplasms genetics, Kidney Neoplasms pathology, Neoplasm Metastasis genetics
- Abstract
The hallmark of chromophobe renal cell carcinoma is multiple chromosomal losses from among chromosomes 1, 2, 6, 10 and 17. Chromophobe renal cell carcinoma with distant metastases or sarcomatoid transformation are uncommon and little is known about their chromosomal abnormalities. We collected six sarcomatoid chromophobe renal cell carcinomas and three primary chromophobe renal cell carcinomas with distant metastases. A cytogenetic analysis by fluorescent in situ hybridization on paraffin-embedded tissue was performed using centromeric probes for chromosomes 1, 2, 6, 10 and 17. We found more than one signal in four of six (66%) sarcomatoid chromophobe renal cell carcinomas, in both sarcomatoid and adjacent epithelial components. Both primary chromophobe renal cell carcinomas and matched metastases showed single signals for all chromosomes studied in two cases and no abnormalities in the remaining case. We concluded that: (1) both epithelial and sarcomatoid components of sarcomatoid chromophobe renal cell carcinoma show different genetic abnormalities from those characteristic of chromophobe renal cell carcinoma; (2) sarcomatoid chromophobe renal cell carcinomas frequently have multiple gains (polysomy) of chromosomes 1, 2, 6, 10 and 17; (3) distant metastases show the same genetic patterns, usually chromosomal losses (monosomy), found in the primary tumors.
- Published
- 2007
- Full Text
- View/download PDF
11. [Diagnostic and prognostic markers in renal tumors].
- Author
-
Martignoni G, Remo A, Pea M, Cossu Rocca P, Brunelli M, Gobbo S, Bonetti F, and Menestrina F
- Subjects
- Biomarkers, Tumor analysis, Humans, Kidney Neoplasms chemistry, Prognosis, Kidney Neoplasms pathology
- Published
- 2005
12. CD10 is expressed in a subset of chromophobe renal cell carcinomas.
- Author
-
Martignoni G, Pea M, Brunelli M, Chilosi M, Zamó A, Bertaso M, Cossu-Rocca P, Eble JN, Mikuz G, Puppa G, Badoual C, Ficarra V, Novella G, and Bonetti F
- Subjects
- Adenocarcinoma, Clear Cell metabolism, Adenocarcinoma, Clear Cell pathology, Adult, Aged, Blotting, Western, Carcinoma, Papillary metabolism, Carcinoma, Renal Cell metabolism, Female, Humans, Immunohistochemistry, Kidney Neoplasms metabolism, Male, Middle Aged, Parvalbumins analysis, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology, Neprilysin biosynthesis
- Abstract
CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P=0.003) and mitotic figures (P=0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas.
- Published
- 2004
- Full Text
- View/download PDF
13. Oncocytoma-like angiomyolipoma. A clinicopathologic and immunohistochemical study of 2 cases.
- Author
-
Martignoni G, Pea M, Bonetti F, Brunelli M, and Eble JN
- Subjects
- Adenoma, Oxyphilic chemistry, Adenoma, Oxyphilic surgery, Adult, Angiomyolipoma chemistry, Angiomyolipoma surgery, Antigens, Neoplasm, Female, Humans, Immunohistochemistry, Immunophenotyping, Kidney Neoplasms chemistry, Kidney Neoplasms surgery, Male, Melanoma-Specific Antigens, Middle Aged, Neoplasm Proteins analysis, Neoplasms, Multiple Primary chemistry, Neoplasms, Multiple Primary surgery, Neoplasms, Second Primary chemistry, Neoplasms, Second Primary surgery, Treatment Outcome, Adenoma, Oxyphilic pathology, Angiomyolipoma pathology, Kidney Neoplasms pathology, Neoplasms, Multiple Primary pathology, Neoplasms, Second Primary pathology
- Abstract
We report the clinical, pathologic, and immunohistochemical features of an unusual tumor of the kidney composed of densely eosinophilic, polygonal epithelioid cells. The patients were a 56-year-old woman and a 35-year-old man. The renal tumors were discovered during follow-up for breast carcinoma and evaluation for abdominal pain, respectively. The tumors closely resembled oncocytoma in routine sections, but were negative for epithelial markers and positive for HMB-45, a pattern of reactions characteristic of angiomyolipoma. In the woman, a single additional microscopic angiomyolipoma was present in the renal parenchyma at a distance from the main tumor. Both patients are alive without recurrence 7 and 10 years after surgery, respectively. Based on clinical, morphologic, and immunophenotypic features, we conclude that these tumors are oncocytoma-like angiomyolipomas.
- Published
- 2002
- Full Text
- View/download PDF
14. Renal disease in adults with TSC2/PKD1 contiguous gene syndrome.
- Author
-
Martignoni G, Bonetti F, Pea M, Tardanico R, Brunelli M, and Eble JN
- Subjects
- Adult, Angiomyolipoma metabolism, Angiomyolipoma pathology, Biomarkers analysis, Child, Fatal Outcome, Female, Humans, Immunohistochemistry, Kidney Neoplasms metabolism, Kidney Neoplasms pathology, Male, Polycystic Kidney, Autosomal Dominant metabolism, Polycystic Kidney, Autosomal Dominant pathology, Proteins metabolism, Repressor Proteins metabolism, Syndrome, TRPP Cation Channels, Tuberous Sclerosis metabolism, Tuberous Sclerosis pathology, Tuberous Sclerosis Complex 2 Protein, Tumor Suppressor Proteins, Angiomyolipoma genetics, Genes, Tumor Suppressor, Kidney Neoplasms genetics, Polycystic Kidney, Autosomal Dominant genetics, Proteins genetics, Repressor Proteins genetics, Tuberous Sclerosis genetics
- Abstract
The most common renal lesions of tuberous sclerosis complex, an autosomal-dominant syndrome resulting from losses of TSC1 (9q34) or TSC2 (16p13.3), are renal cysts and angiomyolipomas. Epithelial neoplasms are less common. The TSC2 gene lies adjacent to PKD1, the major gene responsible for autosomal-dominant polycystic kidney disease. Recently, a deletion mutation disrupting both TSC2 and PKD1 has been described in young children with tuberous sclerosis complex with severe renal cystic disease. This disease has been termed the TSC2/PKD1 contiguous gene syndrome. We describe the lesions in the resected kidneys of two adults with TSC2/PDK1 contiguous gene syndrome, at the time of the nephrectomies: a 31-year-old man and his 44-year-old mother. The four kidneys were enlarged reniform masses composed of cysts lined by flattened, cuboidal, or, infrequently, large deeply eosinophilic epithelial cells. The kidneys also contained numerous classic angiomyolipomas and rare intraglomerular microlesions. In the son the largest tumor was a monotypic epithelioid angiomyolipoma. In the wall of his left renal pelvis there was a plaque-shaped, HMB-45-positive localized lesion of lymphangioleiomyomatosis. This is the first description of the renal lesions in adults with genetically confirmed TSC2/PDK1 contiguous gene syndrome. The pathologic findings highlight the importance of thorough sampling for histology in polycystic kidney diseases and indicate that the observation of an angiomyolipoma in biopsy material from patients with enlarged cystic kidneys should suggest the diagnosis of TSC2/PKD1 contiguous gene syndrome, even in cases without ultrasonographic and macroscopic evidence of angiomyolipoma.
- Published
- 2002
- Full Text
- View/download PDF
15. Parvalbumin is constantly expressed in chromophobe renal carcinoma.
- Author
-
Martignoni G, Pea M, Chilosi M, Brunelli M, Scarpa A, Colato C, Tardanico R, Zamboni G, and Bonetti F
- Subjects
- Calbindin 1, Calbindins, Carcinoma, Renal Cell metabolism, Humans, Immunohistochemistry, Kidney chemistry, Kidney embryology, Kidney pathology, Kidney Neoplasms metabolism, S100 Calcium Binding Protein G analysis, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology, Parvalbumins biosynthesis
- Abstract
Chromophobe renal carcinoma is composed of neoplastic cell showing several features similar to those found in the intercalated cells of the collecting ducts. Because the distal nephron expresses calcium-binding proteins playing a role in calcium homeostasis, we reasoned that these proteins could be expressed by chromophobe carcinoma and therefore represent a diagnostic marker. We studied the immunohistochemical expression of different calcium-binding proteins (parvalbumin, calbindin-D28K, and calretinin) in 140 renal tumors, including 75 conventional (clear cell) carcinomas, 32 chromophobe carcinomas, 17 papillary renal cell carcinomas, and 16 oncocytomas. Parvalbumin was strongly positive in all primary chromophobe carcinomas and in one pancreatic metastasis; it was positive in 11 of 16 oncocytomas and absent in conventional (clear cell) and papillary renal cell carcinomas, either primary or metastatic. Calbindin-D28K and calretinin were negative in all tumors, with the exception of two chromophobe carcinomas, four oncocytomas, and two papillary renal cell carcinomas showing inconspicuous calretinin expression. Our data demonstrate that parvalbumin may be a suitable marker for distinguishing primary and metastatic chromophobe carcinoma from conventional (clear cell) and papillary renal cell carcinoma. Moreover, they suggest a relationship between chromophobe renal carcinoma and renal oncocytoma and indicate that chromophobe carcinoma exhibits differentiation toward the collecting-duct phenotype.
- Published
- 2001
- Full Text
- View/download PDF
16. Renal angiomyolipoma with epithelioid sarcomatous transformation and metastases: demonstration of the same genetic defects in the primary and metastatic lesions.
- Author
-
Martignoni G, Pea M, Rigaud G, Manfrin E, Colato C, Zamboni G, Scarpa A, Tardanico R, Roncalli M, and Bonetti F
- Subjects
- Alleles, Angiomyolipoma surgery, Biomarkers, Tumor, Carcinoma, Renal Cell pathology, Chromosomes, Human, Pair 16 genetics, DNA, Neoplasm analysis, Female, Follow-Up Studies, Genotype, Humans, Immunohistochemistry, Kidney diagnostic imaging, Kidney pathology, Kidney Neoplasms surgery, Microsatellite Repeats, Middle Aged, Neoplasm Recurrence, Local pathology, Neoplasms, Multiple Primary pathology, Nephrectomy, Polymerase Chain Reaction, Time Factors, Tomography, X-Ray Computed, Abdominal Neoplasms pathology, Abdominal Neoplasms secondary, Angiomyolipoma genetics, Angiomyolipoma pathology, Kidney Neoplasms genetics, Kidney Neoplasms pathology, Lung Neoplasms pathology, Lung Neoplasms secondary
- Abstract
Angiomyolipoma (AML) is a benign neoplasm that occurs either sporadically or in patients with tuberous sclerosis complex (TSC) and shows frequent allelic losses at chromosome arm 16p. It has been suggested recently that the melanogenesis marker-positive perivascular epithelioid cell (PEC) has been found consistently in AML. The authors report a 50-year-old woman without evidence of TSC affected by classic renal AML containing an area composed of atypical epithelioid cells with the same morphoimmunophenotypic characters of PEC. After 7 years from surgical removal of the lesion, the patient developed a local recurrence and successive lung and abdominal metastases that showed morphologic and immunohistochemical features overlapping those of the epithelioid area of the previously removed AML. Genetic analysis showed that the classic AML and its epithelioid area as well as the pulmonary and abdominal metastases shared the same allelic loss on chromosome arm 16p. Based on these findings, the authors view this case as evidence of a malignant transformation of a classic AML with morphologic, immunophenotypic, and genetic demonstration of its clonal origin.
- Published
- 2000
- Full Text
- View/download PDF
17. Carcinomalike monotypic epithelioid angiomyolipoma in patients without evidence of tuberous sclerosis: a clinicopathologic and genetic study.
- Author
-
Martignoni G, Pea M, Bonetti F, Zamboni G, Carbonara C, Longa L, Zancanaro C, Maran M, Brisigotti M, and Mariuzzi GM
- Subjects
- Adult, Angiomyolipoma genetics, Angiomyolipoma metabolism, Angiomyolipoma ultrastructure, Antigens, Neoplasm metabolism, Biomarkers, Tumor metabolism, Chromosome Deletion, Fatal Outcome, Female, Heterozygote, Humans, Immunohistochemistry, Kidney Neoplasms genetics, Kidney Neoplasms metabolism, Kidney Neoplasms ultrastructure, Male, Melanoma-Specific Antigens, Microscopy, Electron, Middle Aged, Neoplasm Proteins metabolism, Proteins genetics, Repressor Proteins genetics, Tuberous Sclerosis genetics, Tuberous Sclerosis metabolism, Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Tumor Suppressor Proteins, Angiomyolipoma pathology, Kidney Neoplasms pathology, Tuberous Sclerosis diagnosis
- Abstract
We report the clinicopathologic, immunohistochemical, ultrastructural, and genetic features of an unusual renal tumor composed of large, atypical, densely packed, clear/eosinophilic epithelioid cells. Three patients, two men and one woman (ages 31, 36, and 60 years of age, respectively), had abdominal pain. Morphologically, all cases showed aggressive features (largeness, atypical cells, sarcomatoid features, necrosis, and, in one case, invasion of the renal vein). Despite the marked morphologic resemblance of these tumors to high-grade sarcomatoid renal cell carcinoma, their phenotype (HMB45+, CD68+/-, actin+/-, and vimentin and keratin negative) is in contrast to that observed in epithelial tumors and parallels the phenotypic profile of angiomyolipoma. Ultrastructural analysis showed the presence of glycogen, mitochondria, and prominent electron-dense, membrane-bound granules in the neoplastic cells, and the absence of melanosomes or premelanosomes. Genetic study, performed using polymerase chain reaction from paraffin sections, showed a loss of heterozygosity at the TSC2-containing region on 16p in one case, and on 3p in two cases, showing that multiple genetic alterations are taking place in these tumors. Follow-up has shown local recurrence in one case after 6 years, and the patient died 1 year later of cardiorespiratory failure. The other two patients are well after 26 and 10 months. All three patients were evaluated for signs of tuberous sclerosis, and findings were negative. We suggest that these tumors should be considered close relatives of the angiomyolipoma variants, composed purely of perivascular epithelioid cells. More cases and longer follow-up durations are needed to fully evaluate its prognostic implication.
- Published
- 1998
- Full Text
- View/download PDF
18. Apparent renal cell carcinomas in tuberous sclerosis are heterogeneous: the identification of malignant epithelioid angiomyolipoma.
- Author
-
Pea M, Bonetti F, Martignoni G, Henske EP, Manfrin E, Colato C, and Bernstein J
- Subjects
- Adenoma, Oxyphilic diagnosis, Adenoma, Oxyphilic physiopathology, Adolescent, Adult, Angiomyolipoma diagnosis, Angiomyolipoma physiopathology, Carcinoma, Renal Cell diagnosis, Carcinoma, Renal Cell physiopathology, Diagnosis, Differential, Female, Humans, Kidney Neoplasms diagnosis, Kidney Neoplasms physiopathology, Male, Tuberous Sclerosis physiopathology, Adenoma, Oxyphilic pathology, Angiomyolipoma pathology, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology, Tuberous Sclerosis pathology
- Abstract
Renal epithelial tumors (carcinoma and oncocytoma) have been reported with higher a frequency than expected in patients with the tuberous sclerosis complex. However, the recent identification of a monotypic, epithelioid variant of angiomyolipoma, closely simulating renal cell carcinoma, has cast doubt on the real frequency of carcinoma. Immunohistochemical analysis with a panel of antibodies, including melanogenesis marker HMB45, can discriminate between carcinoma and carcinoma-like angiomyolipoma. We studied five tumors previously reported as carcinoma and found that only one of them showed an immunohistochemical phenotype indicative of an epithelial tumor (Ker+, HMB45-). Three tumors exhibited a phenotype compatible with the monotypic epithelioid variant of angiomyolipoma (HMB45+, Ker-), and two of the three patients died of metastatic disease. The last patient had unusual clinical features, and the tumor was positive both for HMB45 and keratin. It is concluded that (1) renal cell carcinoma is less common in tuberous sclerosis complex than previously believed, (2) some cases called renal cell carcinoma probably represent a monotypic, epithelioid variant of angiomyolipoma, and (3) epithelioid angiomyolipoma is a potentially malignant tumor with invasion and metastases. These findings indicate that all reported renal carcinomas in tuberous sclerosis complex, therefore, must be reevaluated.
- Published
- 1998
- Full Text
- View/download PDF
19. Clear cell ("sugar") tumor of the lung is a lesion strictly related to angiomyolipoma--the concept of a family of lesions characterized by the presence of the perivascular epithelioid cells (PEC).
- Author
-
Bonetti F, Pea M, Martignoni G, Doglioni C, Zamboni G, Capelli P, Rimondi P, and Andrion A
- Subjects
- Adult, Angiomyolipoma chemistry, Blood Vessels cytology, Female, Glycogen analysis, Humans, Immunohistochemistry, Kidney Neoplasms chemistry, Lung Neoplasms chemistry, Male, Middle Aged, Angiomyolipoma pathology, Epithelioid Cells pathology, Kidney Neoplasms pathology, Lung Neoplasms pathology
- Abstract
We report a comparative study of 3 clear cell tumors of the lung (CCTL) and 3 angiomyolipomas (AML) of the kidney. Morphological analysis shows that the cells of CCTL are identical to the perivascular epithelioid component of AML. Phenotypically they both consistently expressed melanoma-associated antigens recognized by Moabs HMB45 and HMSA-1, while they were negative for HMSA-5. A minority of cells also expressed S-100 protein, vimentin and actin. In addition, one case of CCTL showed mature adipose tissue entrapped in the proliferation, thus suggesting an intermediate form between CCTL and AML. Based on morphological and phenotypical similarities, it is suggested that CCTL and AML belong to the same family of lesions, characterized by the presence of a peculiar muscle cell, expressing different melanoma-associated antigens.
- Published
- 1994
- Full Text
- View/download PDF
20. Preoperative diagnosis of renal angiomyolipoma: fine needle aspiration cytology and immunocytochemical characterization.
- Author
-
Bonzanini M, Pea M, Martignoni G, Zamboni G, Capelli P, Bernardello F, and Bonetti F
- Subjects
- Actins analysis, Aged, Angiomyolipoma diagnostic imaging, Angiomyolipoma pathology, Angiomyolipoma surgery, Biopsy, Needle, Cell Nucleus pathology, Female, Humans, Immunohistochemistry, Intermediate Filament Proteins analysis, Kidney Neoplasms diagnostic imaging, Kidney Neoplasms pathology, Kidney Neoplasms surgery, Male, Middle Aged, Muscle, Smooth pathology, Nephrectomy, Tomography, X-Ray Computed, Angiomyolipoma diagnosis, Kidney Neoplasms diagnosis
- Abstract
A preoperative diagnosis of renal angiomyolipoma (AML) is of great importance for a correct management of these patients with this tumor. In fact when the lesion is small and asymptomatic a conservative approach may be considered. We have evaluated the radiographic and fine needle aspiration cytology (FNAB) findings in 8 cases of AML. In 3 cases both radiology and cytology were suggestive of carcinoma and thus the patients underwent surgery. In one case both techniques suggested AML but surgery was performed because the lesion was large and symptomatic. In 4 cases where both radiology and cytology suggested AML no surgery was performed. Follow-up data are consistent with the benign nature of the lesions. The immunocytochemical analysis of the FNAB with a panel of antibodies including keratin, vimentin, actin and HMB-45 was indicative of AML in 7 of 8 cases, including 2 of the 3 cases misdiagnosed as carcinomas. The presence of HMB-45-positive perivascular epithelioid cells in the FNABs was the most significant finding. It is concluded that immunocytochemical analysis of FNAB with this monoclonal antibody panel can increase the accuracy of preoperative diagnosis of AML, and allow consideration of a conservative approach in selected cases.
- Published
- 1994
- Full Text
- View/download PDF
21. Sarcomatoid tumors of the kidney.
- Author
-
Bonetti F, Pea M, Martignoni G, and Bonzanini M
- Subjects
- Biopsy, Needle, Diagnosis, Differential, Humans, Angiomyolipoma pathology, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology, Sarcoma pathology
- Published
- 1994
- Full Text
- View/download PDF
22. Diagnostic and therapeutic problems in multicentric renal angiomyolipoma.
- Author
-
Tallarigo C, Baldassarre R, Bianchi G, Comunale L, Olivo G, Pea M, Bonetti F, Martignoni G, Zamboni G, and Mobilio G
- Subjects
- Adolescent, Adult, Antibodies, Monoclonal, Antigens, Neoplasm analysis, Female, Hemangioma surgery, Humans, Immunohistochemistry, Kidney Neoplasms surgery, Lipoma surgery, Male, Middle Aged, Neoplasm Invasiveness, Hemangioma pathology, Kidney Neoplasms pathology, Lipoma pathology
- Abstract
Multicentric renal angiomyolipoma is a rare form of benign tumor. However, its effective incidence as evaluated in autopsy studies may be as high as 8%. There are 2 main types of renal angiomyolipoma, that is isolated forms and those associated with other diseases, such as phakomatosis, polycystic kidneys and fibromuscular dysplasia. The tumor may also display malignant behavior with local invasiveness and regional lymph node involvement. However, the clinical course is benign and multicentricity is important for prognosis. Histopathological diagnosis often is difficult. Immunohistochemical analysis of surgical specimens using a panel of monoclonal antibodies, including HMB-45 and actin, enabled us to make a definitive diagnosis in 3 cases of multicentric renal angiomyolipoma.
- Published
- 1992
- Full Text
- View/download PDF
23. PEC and sugar.
- Author
-
Bonetti F, Pea M, Martignoni G, and Zamboni G
- Subjects
- Humans, Melanocytes, Terminology as Topic, Hemangioma pathology, Kidney Neoplasms pathology, Lipoma pathology, Lung Neoplasms pathology, Lymphangiomyoma pathology
- Published
- 1992
- Full Text
- View/download PDF
24. Melanocyte-marker-HMB-45 is regularly expressed in angiomyolipoma of the kidney.
- Author
-
Pea M, Bonetti F, Zamboni G, Martignoni G, Riva M, Colombari R, Mombello A, Bonzanini M, Scarpa A, and Ghimenton C
- Subjects
- Carcinoma, Renal Cell diagnosis, Carcinoma, Renal Cell immunology, Diagnosis, Differential, Hemangioma diagnosis, Humans, Immunohistochemistry, Kidney Neoplasms diagnosis, Lipoma diagnosis, Retroperitoneal Neoplasms diagnosis, Retroperitoneal Neoplasms immunology, Sarcoma diagnosis, Sarcoma immunology, Wilms Tumor diagnosis, Wilms Tumor immunology, Antibodies, Monoclonal immunology, Biomarkers, Tumor analysis, Hemangioma immunology, Kidney Neoplasms immunology, Lipoma immunology, Melanocytes immunology
- Abstract
HMB-45 (melanocytic cell-specific monoclonal antibody) immunoreactivity was investigated in 10 cases of angiomyolipoma (AML) (1 with massive regional lymph node involvement) of the kidney and detected in all of them. No HMB-45 immunoreactivity was found in other tumors of the region which can occasionally be confused with AML, such as renal cell carcinoma, Wilms' tumor, and retroperitoneal sarcoma (leiomyosarcoma and liposarcoma). These findings indicate that HMB-45 is not a melanocyte-restricted marker and suggest that its expression might be useful in distinguishing AML from other tumors of the kidney and retroperitoneum.
- Published
- 1991
- Full Text
- View/download PDF
25. Cathepsin-K immunoreactivity distinguishes MiTF/TFE family renal translocation carcinomas from other renal carcinomas
- Author
-
Ondřej Hes, Marco Chilosi, Stefano Gobbo, Franco Bonetti, Diego Segala, Matteo Brunelli, George J. Netto, Guido Martignoni, Maurizio Pea, Claudio Doglioni, Chin Chen Pan, Pedram Argani, Martignoni, G., Pea, M., Gobbo, S., Brunelli, M., Bonetti, F., Segala, D., Pan Chin, Chen, Netto, G., Doglioni, Claudio, Hes, O., Argani, P., and Chilosi, M.
- Subjects
Adult ,congenital, hereditary, and neonatal diseases and abnormalities ,Pathology ,medicine.medical_specialty ,Adolescent ,Oncogene Proteins, Fusion ,Cathepsin K ,Translocation ,Socio-culturale ,Chromosomal translocation ,TFE3 ,Biology ,Microphthalmia ,Translocation, Genetic ,Pathology and Forensic Medicine ,Fusion gene ,Young Adult ,medicine ,Biological analysis ,Biomarkers, Tumor ,Humans ,Child ,Transcription factor ,Carcinoma, Renal Cell ,Aged ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Carcinoma ,Renal Cell ,Cathepsins biosynthesis ,Gene Expression Regulation ,Neoplastic ,Immunohistochemistry ,Kidney Neoplasms ,Middle Aged ,Oncogene Proteins ,Fusion/genetics/metabolism ,Tissue Array Analysis ,Genetic Tumor Markers ,medicine.disease ,Microphthalmia-associated transcription factor ,Fusion protein ,Cathepsins ,Gene Expression Regulation, Neoplastic ,Child, Preschool ,Cancer research ,TFEB - Abstract
The microphthalmia transcription factor/transcription factor E (TFE)-family translocation renal cell carcinomas bear specific translocations that result in overexpression of TFE3 or TFEB. TFE3 fusion gene product overexpression occurs as consequence of different translocations involving chromosome Xp11.2, whereas TFEB overexpression is the result of the specific translocation t(6; 11)(p21;q12), which fuses the Alpha gene to TFEB. Both TFE3 and TFEB are closely related members of the microphthalmia transcription factor/TFE-family, which also includes TFEC and microphthalmia transcription factor. These transcription factors have overlapping transcriptional targets. Overexpression of microphthalmia transcription factor has been shown to mediate the expression of cathepsin-K in osteoclasts. We hypothesize that the overexpression of the related TFE3 fusion proteins and TFEB in translocation renal cell carcinomas may have the same effect. We studied cathepsin-K in 17 cytogenetically confirmed microphthalmia transcription factor/TFE-family translocation renal cell carcinomas. Seven cases showed a t(6; 11)(p21; q12), ten cases showed translocations involving Xp11.2; five cases t(X; 1)(p11;q21) resulting in a PRCC-TFE3 gene fusion; three cases t(X; 1)(p11;p34) resulting in a PSF-TFE3 gene fusion, one t(X; 17)(p11;q25) resulting in an ASPL-TFE3 gene fusion, and one t(X; 3)(p11;q23) with an unknown TFE3 gene fusion. As control we analyzed cathepsin-K in 210 clear cell, 40 papillary, 25 chromophobe renal cell carcinomas and 30 oncocytomas. All seven TFEB translocation renal cell carcinomas were labeled for cathepsin-K. Among the cytogenetically confirmed TFE3 translocation renal cell carcinomas, 6 out of 10 were positive. None of the other renal neoplasms expressed cathepsin-K. We conclude the following: (1) cathepsin-K is consistently and strongly expressed in TFEB translocation renal cell carcinomas and in 6 of 10 TFE3 translocation renal cell carcinomas. (2) Cathepsin-K immunolabeling in both TFE3 and TFEB translocation renal cell carcinomas distinguishes these neoplasms from the more common adult renal cell carcinomas, and may be a specific marker of these neoplasms. (3) These results further support the concept that the overexpression of TFE3 or TFEB in these neoplasms activates the expression of genes normally regulated by microphthalmia transcription factor in other cell types. Modern Pathology (2009) 22, 1016-1022; doi: 10.1038/modpathol.2009.58; published online 24 April 2009 ZR 0 ZS 0 Z8 4 ZB 41
- Published
- 2009
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.