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Supplemental Digital Content is available in the text.The mutation status of KITor PDGFRAnotoriously affects the response of advanced gastrointestinal stromal tumors (GISTs) to tyrosine kinase inhibitors. Conversely, it is currently still unclear whether mutation status impinges on the prognosis of localized, untreated GISTs. Hence, at present, this variable is not included in decision making for adjuvant therapy. A series of 451 primary localized GISTs were analyzed for KIT, PDGFRA, and BRAFmutations. Univariable and multivariable analyses and a backward selection procedure were used to assess the impact of mutation status on overall survival and to identify prognostically homogenous groups. Mutation was a significant prognostic indicator of overall survival in naive, localized GISTs (P<0.001): KIT-mutated patients had a worse outcome than PDGFRA-mutated or triple-negative (KIT, PDGFRA, BRAFwild-type) cases. Multivariable Cox regression models allowed us to identify 3 molecular risk groups: group I exhibited the best outcome and included PDGFRAexon 12, BRAF, and KITexon 13-mutated cases; group II, of intermediate clinical phenotype (HR=3.06), included triple-negative, KITexon 17, PDGFRAexon 18 D842V, and PDGFRAexon 14-mutated cases; group III displayed the worst outcome (hazard ratio=4.52), and comprised KITexon 9 and exon 11 and PDGFRAexon 18 mutations apart from D842V. This study highlights the prognostic impact of mutation status on the natural course of GIST and suggests that the molecular prognostic grouping may complement the conventional clinicopathologic risk stratification criteria in decision making for adjuvant therapy.

Sarcomas are rare, heterogenous, and often difficult to classify. A large proportion of sarcomas are associated with specific molecular genetic lesions such as translocations, mutations, and amplifications, which are helpful in the diagnosis of individual cases. However, the exact impact of molecular genetics on the final diagnosis of sarcomas is unknown. In this study, all soft tissue and visceral sarcomas arising in patients living in 3 European regions in 2 countries (representing 13 million inhabitants) were collected and reviewed during 2 consecutive years. A molecular analysis was performed for all suspicions of sarcomas with specific genetic lesions mutations of KITPDGFRAin gastrointestinal stromal tumors (GISTs), reciprocal translocation, or amplification of MDM2in atypical lipomatous tumors, well-differentiated liposarcoma-dedifferentiated liposarcoma (ALTWDLPS-DDLPS). To evaluate the impact of molecular tests, a premolecular analysis diagnosis was proposed with 3 categories of certainty: certain, probable, or possible. A molecular analysis was performed in 7631484 tumors corresponding to 295 cases in which GIST was suspected, 248 sarcomas with a suspicion of translocation, and 220 cases in which ALTWDLPS-DDLPS was suspected. Molecular analysis was found to be useful (confirms a probable diagnosis) in 11 (4) GISTs, 62 (26) suspicions of translocation, and 66 (31) suspicions of ALTWDLPS-DDLPS; and necessary (allows a possible diagnosis) in 2 (<1) GISTs, 31 (12) suspicions of translocation, and 19 (9) suspicions of ALTWDLPS-DDLPS. This study performed in an epidemiological setting demonstrates the significant impact of molecular analysis on the final sarcoma diagnosis and favors such an analysis on any tumor with a suspicion of a specific genomic abnormality and for which the diagnosis is uncertain.

The MYCNoncogene encodes a phosphoprotein that acts as a transcription factor and is involved in the regulation of cell proliferation and differentiation in normal as well as in cancer cells.MYCNamplification and expression have been reported in various tumours, including neuroblastoma and lung cancer, but little is known about its expression in human rhabdomyosarcoma. MYCNexpression and amplification were studied in five alveolar and five embryonal rhabdomyosarcoma cell lines and in 19 tumour biopsies. All the cell lines studied expressed MYCNRNA, as demonstrated by northern blot analysis and RT‐PCR, but the oncogene was amplified in only one. Similarly, MYCNprotein was detected in all cell lines by western blot analysis, with higher levels of expression in alveolar than in embryonal rhabdomyosarcoma cells. RT‐PCR analysis of tumour samples demonstrated 18/19 cases positive for MYCNRNA. Although MYCNexpression was higher in alveolar than in embryonal rhabdomyosarcoma cell lines, no clear relationship between histology and level of MYCNexpression could be established in this tumour series. These data suggest that MYCNexpression is a common feature of rhabdomyosarcoma, independent of gene amplification and without a clear relationship with specific histological and clinical features. Copyright © 2002 John Wiley & Sons, Ltd.

Ovarian ablation is the oldest form of systemic treatment of breast cancer and consists of removal of the main source of estrogen biosynthesis in premenopausal women. Over the last century several different means of stopping ovarian function have been studied: surgical oophorectomy, ovarian irradiation, and more recently, chemical castration by gonadotropin-releasing hormone analog therapy. In unselected patients the response rate to ovarian ablation is of about 35% but the likelihood of response is considerably higher for patients with hormonal receptor-positive tumors, the therapy being most effective in women who are actively menstruating. In spite of this evidence, the role of ovarian ablation in the management of early-stage breast cancer still remains controversial. Here we review current evidence supporting the value of this ablative procedure as an adjuvant and update ongoing clinical research to refine our knowledge about its use.

Medulloblastoma is an embryonal neuroepithelial tumor that affects mainly childhood and more rarely adults. Medulloblastoma occurring as multiple nodules at diagnosis is a rare and tricky presentation. Here, we describe the case of a previously healthy 47-year-old woman with multiple posterior fossa cerebellar tumors. Histological, immunohistochemical, and molecular analyses were performed to best characterize the two excised lesions. The histopathological analysis revealed different variants of medulloblastoma in the excised nodules, one being extensive nodularity, rare in adults, and the other desmoplastic/nodular with areas of anaplasia. Immunostains and molecular analysis classified both nodules as SHH medulloblastoma. Adult medulloblastoma is extremely rare. Important differences exist between adult medulloblastoma and medulloblastoma arising in children and infants. Such differences are in location, distribution of histological variants and of molecular subgroups, survival rates, and therapeutic options. An extensive morphological and molecular characterization of such rare tumors is necessary to choice the best-tailored therapy.