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The microphthalmia transcription factor/transcription factor E (TFE)-family translocation renal cell carcinomas bear specific translocations that result in overexpression of TFE3 or TFEB. TFE3fusion 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 Alphagene 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–TFE3gene fusion; three cases t(X;1)(p11;p34) resulting in a PSF–TFE3gene fusion, one t(X;17)(p11;q25) resulting in an ASPL–TFE3gene fusion, and one t(X;3)(p11;q23) with an unknown TFE3gene 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.

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

OBJECTIVE: To evaluate the roles of the CDKN1C (P57KIP2) gene, which encodes for the cyclin-dependent kinase inhibitor CDNC, and the TP53 tumor suppressor gene in adrenal tumorigenesis, as a means of investigating the molecular basis of sporadic adrenal tumors, which is unknown. DESIGN: Screening for the presence CDKN1C and TP53 mutations and analyzing the expression pattern of CDNC, P53 and its downstream effector CDN1 (P21WAF1/CIP1) in a series of 79 sporadic adrenal tumors. METHODS: Single-strand conformation polymorphism and sequencing were used for mutation analysis of CDKN1C and TP53 in blood and adrenal tissue samples. In a subgroup of 48 tissues, CDKN1C expression was evaluated by RT-PCR and immunohistochemistry. Immunohistochemical analysis of P53 and CDN1 was performed. RESULTS: No somatic mutations of CDKN1C were found in the tumors analyzed, in spite of low/absent CDNC expression in adrenocortical adenomas and carcinomas. Mutations in the TP53 gene were present in 70% of adrenocortical carcinomas, associated with abnormal P53 and CDN1 expression, but not in benign neoplasms. In the normal adrenal cortex, CDNC expression was strictly nuclear and confined to the cortical zone (i.e. zona glomerulosa and reticularis), with no staining in the medulla. CONCLUSIONS: Mutations in the TP53 gene are frequent in adrenocortical carcinomas and might be used as a marker of malignancy. In the normal adrenal cortex, the zone-specific pattern of expression of CDNC suggests a role in adrenal differentiation.

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.

Background: Over the last few years, estrogen receptor (ER) determination by immunohistochemistry (ER-ICA) has been extensively used, but it still remains to be established whether this method can replace the standard biochemical technique using dextran-coated charcoal (ERDCC).

The immunoperoxidase staining of normal and hyperplastic prostatic epithelium for Prostate Specific Antigen (PSA) is, with few exceptions, uniform and strong. In contrast to the benign tissue, most reports of prostatic adenocarcinoma demonstrated an apparent correlation between staining-variability and increasing tumour grades. Decreased PAP staining may be related to incorrect manipulation of prostatic tissue. Finally there are many tumours and pseudotumours of the prostate in which the PSA stain is regularly negative. In the differential diagnosis of prostate tumour, both PSA and PAP (Prostatic Acid Phosphatase) stains should be performed. It is mandatory that the stains be interpreted in the appropriate histologic and clinicopathologic setting with due consideration of positive and negative staining.

— We report the results of a retrospective study of two groups of patients affected by locally advanced bladder cancer: the first group was submitted to adjuvant chemotherapy with Cisplatin and Methotrexate after cystectomy and the second group was submitted to neoadjuvant chemotherapy with the same scheme following radical cystectomy. The validity of the study is given by the homogeneity of the two groups for period of recruitment, number of patients, patient's age, stage of disease and treatment. The overall survival of 5 years in the first group was 30%, while the 5-year survival rate of the second group was 38%, 63% and 17% for all the patients, the responders and the nonresponders respectively. No significant difference in terms of survival was found between the two groups, but the results of the neoadjuvant approach may be influenced by clinical staging errors. The chemosensitivity, that can be assessed only with the neoadjuvant treatment, is the main prognostic factor.

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.

Zusammenfassung In der vorliegenden Studie wird über die Ergebnisse verschiedener Behandlungsverfahren bei 20 Patienten mit hereditärem angioneurotischem Ödem berichtet. Die Wirksamkeit des Esterase-Inhibitors Trancxam-Säure zur Verhütung des Ödems wurde bei 15 Patienten erprobt. Bei 12 der 15 Patienten war Trancxam-Säure wirksam und ohne wesentliche Nebenwirkungen. 15 schwere Anfälle von angioneurotischem Ödem wurden behandelt mit intravenösen Infusionen entweder von Kallikrein-Inhibitor (8 Fälle) oder einem Konzentrat eines C1-Esterase-Inhibitors (7 Fälle). Nach dem Kallikrein-Inhibitor blieb nur in 1 Fall ein Erfolg aus. Das Konzentrat von C 1-Esterase-Inhibitor zeigte sich äußerst wirksam in der Behandlung akuter Anfälle (1 Mißerfolg infolge zu geringer Dosierung). Nebenwirkungen wurden bei beiden Behandlungsverfahren nicht beobachtet, jedoch konnte die Besserung mit Hilfe des C 1-Esterase-Inhibitors schneller erreicht werden. Die Serumspiegel von C 4- und C 1-Esterase-Inhibitor und die Aktivität von C 1-Esterase-Inhibitor vor und nach Langzeitprophylaxe und nach Therapie akuter Anfälle wurden untersucht.

Es wird über 3 Familien mit hereditärem angioneurotischem Ödem berichtet. Die Serum-C -INH- und C4-Spiegel wurden bei 23 Familienmitgliedern immunochemisch bestimmt: Bei 6 Personen mit typischen Symptomen von HANE und einem Familienmitglied ohne Krankheitserscheinungen wurden niedrige C -INH- und C4-Spiegel gefunden. Vergleichsweise sind die Normalbereiche der beiden Proteine für Erwachsene, Kinder und Neugeborene angegeben. Die Autoren weisen auf die Bedeutung und Wichtigkeit einer rechtzeitigen Diagnose und Therapie hin.