Annick Vieillefond

Clear-cell papillary renal cell carcinoma: 24 cases of a distinct low-grade renal tumour and a comparative genomic hybridization array study of seven cases

Adam J, Couturier J, Molinié V, Vieillefond A & Sibony Mu2028(2011) Histopathology58, 1064–1071u2028Clear‐cell papillary renal cell carcinoma: 24 cases of a distinct low‐grade renal tumour and a comparative genomic hybridization array study of seven cases

Large-scale Real-time Reverse Transcription-PCR Approach of Angiogenic Pathways in Human Transitional Cell Carcinoma of the Bladder: Identification of VEGFA as a Major Independent Prognostic Marker

BACKGROUNDnActors of the angiogenesis pathways are targets for the new promising targeted therapies already used in several malignancies. In bladder cancer, antiangiogenic molecules could also add to already existing treatment options.nnnOBJECTIVEnTo evaluate the involvement of angiogenesis pathways in bladder carcinogenesis and identify new molecular markers having a clinical implication.nnnDESIGN, SETTING, AND PARTICIPANTSnExpression levels of 40 genes involved in angiogenesis were assessed by quantitative real time RT-PCR in 157 urothelial tumour bladder samples obtained from patients who underwent transurethral bladder resection or radical cystectomy between 2001 and 2005. Pathologic tumour staging showed: 73 non-muscle-invasive bladder tumours (30 low-grade pTa, 14 high-grade pTa, and 29 high-grade pT1), and 84 muscle-invasive tumours (> or = pT2), all of high grade. RT-PCR results were associated with a survival analysis.nnnRESULTS AND LIMITATIONSnVEGFA, MET, CXCR4, and IL8 were significantly overexpressed in tumour samples as compared to normal bladder tissue. VEGFA overexpressions were found in 89% of non-muscle-invasive and 66% of muscle-invasive tumour samples. In univariate analysis, for invasive tumours, VEGFA overexpression was associated with a poorer outcome in both overall and disease-free survival (p=0.011 and 0.026 respectively) at a 13-mo median follow-up. Multivariate analysis retained T stage, N status, and VEGFA overexpression as independent prognostic factors in both overall and disease-free survival (p=0.02 and p=0.04, respectively, for VEGFA).nnnCONCLUSIONSnThis study shows that, in bladder cancer, VEGFA status could be used as a prognostic factor at the individual level. VEGFA overexpression could guide a rationalized use of the costly antiangiogenic therapies which could therefore become part of the treatment options in bladder cancer.

Carcinome rénal associé à une translocation MiTF/TFE : présentation de six cas chez l’adulte jeune☆

OBJECTIVEnThe authors present six cases of renal carcinoma associated with MiTF/TFE translocation in young adults. This tumour is one of the newly identified entities of the WHO 2004 classification.nnnMATERIALSnSix patients with MiTF/TFE translocation were identified in a series of 636 adults operated between 2001 and 2005. The diagnosis was based on cytogenetic analysis and immunohistochemistry (IHC) in three patients and IHC alone in the other three patients.nnnRESULTSnFour women and two men between the ages of 28 and 42 years presented a tumour with a mean diameter of 6 cm (range: 3-15 cm). The TNM classification of these tumours was pT1N0 (n=2), pT2N0 (n=1), pT3aN+M0 (n=1), and pT3aN+M+ (n=2). The mean follow-up was 32 months. One M+ patient died six months after the operation, another two pT3 patients developed metastatic disease and pT1 or pT2 patients were alive without recurrence. The histological features comprised a typical papillary architecture with large eosinophil and/or clear cells. IHC showed TFE3 (n=5) or TFEB (n=1) expression. Cytogenetic analysis demonstrated a t(X;1)(p11.2;p34) or t(X;17)(p11.2;q25) translocation in two patients expressing TFE3 and a t(6;11)(p21; q13) translocation in the patient expressing TFEB.nnnCONCLUSIONnRenal carcinoma associated with MiTF/TFE translocation can be diagnosed by IHC. However, cytogenetic analysis on fresh or frozen material allows characterization of the translocation and should be performed on all renal tumours in young adults. Prognosis is related to stage. In the future, the diagnosis of more cases of this type of carcinoma will allow more precise definition of the clinicopathological profile and the most appropriate management.

Hybrid oncocytic/chromophobe renal cell tumours do not display genomic features of chromophobe renal cell carcinomas

Hybrid oncocytic/chromophobe tumours (HOCT) are renal tumours recently described displaying histological features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), raising the question of their precise signification in the RO/ChRCC group. This study aimed to describe clinicopathological features of so called HOCT and to characterise their genomic profile. Five hundred and eighty-three tumours belonging to the ChRCC/RO group were retrospectively reviewed. Twelve tumours that could not be classified as RO or CHRC were considered as HOCT. Hale staining and cytokeratin 7 (CK7) immunostaining were performed. Genomic profile was established by array comparative genomic hybridisation (array-CGH) on frozen samples. Mean age at diagnosis was 70xa0years (range 46–83). No recurrence was observed (median follow-up: 18xa0months; range 9–72). Tumour size ranged from 1 to 11xa0cm. HOCT showed an admixture of RO- and ChRCC-like areas and/or “hybrid” cells with overlapping cytonuclear and/or histochemical features. Hale staining was apical in 50 to 100xa0% of cells, and CK7 was expressed in 10 to 100xa0% of cells. Genomic profile was balanced in seven cases or showed a limited number of random imbalances in five cases, as observed in RO. In no instances were observed the characteristic chromosome losses of ChRCC. These results suggest that so called HOCT are not true hybrid tumours and rather could represent a morphological variant of RO. From a diagnostic perspective, an array-CGH analysis could be performed in ambiguous ChRCC/RO cases to formally exclude the diagnosis of ChRCC.

Identification of CAD as an androgen receptor interactant and an early marker of prostate tumor recurrence

Markers of prostate tumor recurrence after radical prostatectomy are lacking and highly demanded. The androgen receptor (AR) is a nuclear receptor that plays a pivotal role in normal and cancerous prostate tissue. AR interacts with a number of proteins modulating its stability, localization, and activity. To test the hypothesis that an increased expression of AR partners might foster tumor development, we immunopurified AR partners in human tumors xenografted into mice. One of the identified AR partners was the multifunctional enzyme carbamoyl‐phosphate synthetase II, aspartate transcarbamylase, and dihydroorotase (CAD), which catalyzes the 3 initial steps of pyrimidine biosynthesis. We combined experiments in C4‐2, LNCaP, 22RV1, and PC3 human prostate cell lines and analysis of frozen radical prostatectomy samples to study the CAD‐AR interaction. We show here that in prostate tumor cells, CAD fosters AR translocation into the nucleus and stimulates its transcriptional activity. Notably, in radical prostatectomy specimens, CAD expression was not correlated with proliferation markers, but a higher CAD mRNA level was associated with local tumor extension (P= 0.049) and cancer relapse (P=0.017). These results demonstrate an unsuspected function for a key metabolic enzyme and identify CAD as a potential predictive marker of cancer relapse.—Morin, A., Fritsch, L., Mathieu, J. R. R., Gilbert, C., Guarmit, B., Firlej, V., Gallou‐Kabani, C., Vieillefond, A., Delongchamps, N. B., Cabon, F. Identification of CAD as an androgen receptor interactant and an early marker of prostate tumor recurrence. FASEB J. 26, 460–467 (2012). www.fasebj.org

Les sarcomes du cordon spermatique de l’adulte : diagnostic et prise en charge☆

PURPOSEnto clarify the patterns of diagnosis and management of adult spermatic cord sarcoma.nnnPATIENTS AND METHODSnbetween 1996 and 2009, seven patients with spermatic cord sarcoma were treated at Cochin hospital. After updating the pathological diagnosis according to the new classification of sarcoma we found that all patients had well-differentiated or dedifferentiated liposarcoma. We analysed their clinical presentation, management and carcinological outcome.nnnRESULTSnthe patients age ranged from 51 to 77 years, and their follow-up from 7 to 68 months. In five patients, the diagnosis of well-differentiated liposarcoma (lipoma-like) with some dedifferentiated sectors was made straightaway. In the two other patients, the initial diagnosis was that of leiomyosarcoma, which was reconsidered as dedifferentiated liposarcoma according to the cytogenetical and immunohistochemical techniques available since 2005. In 6/7 patients, a tumour resection with an orchiectomy at the same time (four patients) or secondarily (two patients) was performed. In one patient, only a tumour resection, without orchiectomy, was made. Multiple recurrences were observed in the two patients who were initially diagnosed as leiomyosarcoma. They needed multiple reintervention. One of them died after 68 months of evolution, the other one was treated with chemotherapy and died after 47 months of evolution. Four patients are out of recurrence. One patient was lost to follow-up.nnnCONCLUSIONnthe diagnosis of liposarcoma must be considered in all adult patients aged of more than 50 with fatty-shaped or containing fibomuscular nodules paratesticular tumours. The surgeon and the pathologist must be well informed and an early and wide resection of fatty masses of the sperm cord with negative margins is advocated. The quality of resection is crucial but its appreciation and carrying out are difficult. The role of complementary treatments, especially radiotherapy, has to be determined.

Tumeurs rénales hybrides : à propos de deux patients

PURPOSEnRenal hybrid tumors (HT) are characterized by the association of both oncocytes- and chromophobe-cells within the same tumor. They have been reported in patients with Birt-Hogg-Dube (BHD) syndrome. The aim of this report was to describe two cases of HT and summarize recent literature.nnnPATIENT AND METHODnCase study was summarized from the patients medical chart. Review of literature was performed using the National Center for Biotechnology Information (NCBI) database.nnnRESULTSnTwo patients were diagnosed with multiple but small tumors of the kidney, and were treated with partial nephrectomy. Pathological analysis of these tumors showed oncocytoma-like and chromophobe-like cells intermixed in the same stroma.nnnCONCLUSIONSnHT may constitute a spectrum of tumors between renal oncocytoma and chromophobe renal cell carcinoma. From a pragmatic management perspective, it would be appropriate to consider such tumors as chromophobe carcinoma. In case of HT, a genetic study for BHD syndrome can be proposed to family relatives.