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// Sandra Durante 1, * , Silvia Vecchiarelli 2, * , Annalisa Astolfi 1 , Elisa Grassi 2 , Riccardo Casadei 3 , Donatella Santini 4 , Riccardo Panzacchi 4 , Claudio Ricci 3 , Salvatore Serravalle 5 , Giuseppe Tarantino 1 , Mirella Falconi 6 , Gabriella Teti 6 , Valentina Indio 1 , Andrea Pession 5 , Francesco Minni 3 , Guido Biasco 1, 2 , Mariacristina Di Marco 2 1 Giorgio Prodi Cancer Research Centre, University of Bologna, Bologna, Italy 2 Department of Experimental, Diagnostic and Specialty Medicine University of Bologna, Sant’Orsola-Malpighi Hospital, Bologna, Italy 3 Department of Medical and Surgical Sciences, University of Bologna, Sant’Orsola-Malpighi Hospital, Bologna, Italy 4 Pathology Unit, Sant'Orsola-Malpighi Hospital, Bologna, Italy 5 Department of Medical and Surgical Sciences, “Lalla Seragnoli” Hematology-Oncology Unit, University of Bologna, Bologna, Italy 6 DIBINEM—Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy * These authors contributed equally to this work Correspondence to: Annalisa Astolfi, email: annalisa.astolfi@unibo.it Keywords: PDA, IPMN, chromosome 3, NGS, PIK3CA Received: April 11, 2016 Accepted: August 10, 2016 Published: August 22, 2016 ABSTRACT Background: Intraductal papillary mucinous neoplasm (IPMN) is the most common cystic preneoplastic lesion of pancreatic cancer. We used an approach coupling high resolution cytogenetic analysis (Affymetrix Oncoscan FFPE Array) with clinically-oriented bioinformatic interpretation of data to understand the most relevant alterations of precursor lesions at different stages to identify new diagnostic markers. Results: We identified multiple copy number alterations, particularly in lesions with severe dysplasia, with 7 IPMN with low-intermediate dysplasia carrying a nearly normal karyotype and 13 IPMN with complex Karyotype (> 4 alterations), showing high grade dysplasia. A specific gain of chromosome arm 3q was found in IPMN with complex Karyotype (92%). This gain of 3q is particularly interesting for the presence of oncogenes such as PIK3CA, GATA2 and TERC that are part of pathways that deregulate cell growth and promote disease progression. Quantitative PCR and FISH analysis confirmed the data . Further demonstration of the overexpression of the PIK3CA gene supports the identification of this alteration as a possible biomarker in the early identification of patients with IPMN at higher risk for disease progression. Materials and methods: High resolution cytogenetic analysis was performed in 20 formalin fixed paraffin embedded samples of IPMN by Oncoscan FFPE assay. Results were validated by qPCR and FISH analysis. Conclusions: The identification of these markers at an early stage of disease onset could help to identify patients at risk for cancer progression and new candidates for a more specific targeted therapy.

Borderline ovarian tumors are rare low malignant potential neoplasms characterized by the absence of stromal invasion, whose main prognostic factors are stage and type of peritoneal implants. The latter are defined as invasive when cell proliferation invades the underlying tissue (peritoneal surface, omentum and intestinal wall), or noninvasive. It is still unknown if these implants are metastatic spread from the primary ovarian mass or a neoplastic transformation de novo of the peritoneal surface. Mitochondrial DNA sequencing was performed to assess clonality in eight patients presenting both borderline ovarian tumors and implants. In 37.5% of the cases, the same mitochondrial DNA mutation was present in both borderline ovarian tumors and the peritoneal implant, being this evidence that implants may arise as a consequence of a spread from a single ovarian site. Electronic supplementary material The online version of this article (doi:10.1186/s12943-017-0614-y) contains supplementary material, which is available to authorized users.

The most common sites of metastatic differentiated thyroid cancer are the neck lymph nodes, while distant metastases typically involve the lungs, the bones, and less frequently the brain. Uncommon metastatic sites include the liver, adrenal gland, kidney, pancreas, and skin. The epidemiological aspects of thyroid metastases in rare sites are largely unknown and their identification could have a significant impact on patients management. A mini-series of unusual metastatic sites of thyroid carcinoma is proposed as a contribution to current knowledge on anatomopathological characteristics and clinical outcome. Of the six cases that were assessed, the metastases were the following: skin metastases (2), skin and pancreas metastases (1), renal metastasis (1), adrenal metastasis (1), and liver metastasis (1). In our experience, metastases in rare sites do not always represent a negative prognostic factor for disease outcome. In fact they can occur as single distant lesion and if surgically resectable, their treatment can also lead to local disease remission.