Research Activity (2017-2018)
HPV related disease (head & neck and cervical cancer)
We have conducted epidemiological, clinical and molecular studies on HPV-related diseases on individuals affected by benign or malignant head & neck or cervical lesions, as well as on healthy high-risk populations. Regarding head & neck tumours, particularly those developed in the oropharynx, we collaborated with IARC, ISG, and a number of clinical and experimental Units of our Institute. Regarding cervical cancer prevention, we coordinated the NTCC2 study, a large Italian multicentric study aimed to investigate the cross-sectional and longitudinal value of the HPV mRNA and the p16/Ki67 tests as triage test for HPV DNA positivity in cervical screening.
miRNA studies (thymic epithelial tumours, prostate and gastric cancer)
- Identification of a 69-gene signature of miR-145-5p putative target mRNAs as further development of the multicentric study on mature MicroRNA profiling of thymic epithelial tumours.
- Investigation of c-Met/miR-130b axis as a new prognostic marker for prostate cancer risk assessment and as indicator of therapy resistance.
- Identification of a novel miR-204 gene target signature perturbed in gastric cancer and in cholangiocarcinoma.
Immunohistochemical (IHC) studies (breast and gastric cancer)
- IHC analysis of MST1/2 and LATS1/2 expression in neoadjuvant treated (NAT) breast cancer (BC) evidenced that the Hippo kinases localization differently impacts therapy efficacy, being protective when expressed in the tumour cell cytoplasm and in tumour-infiltrating lymphocytes and, conversely, inducing chemoresistance when present in the nucleus as a consequence of their cooperation with the DNA damage response (DDR). Moreover, we evidenced a relationship between DDR biomarkers (namely-H2AX and pChk1) and response to NAT according to Body Mass Index status.
- A multicentric study conducted on a series of advanced gastric cancer treated with first-line chemotherapy showed that the oncogenic YAP/TAZ-Wnt crosstalk may be active in this neoplasia, and confers chemoresistant traits that translate into adverse survival outcomes.
Molecular studies (breast, lung, colorectal, ovarian, and endometrial cancer)
- Logistic regression models have indicated that the cut-off of 2150 copies detected by One-Step Nucleic acid amplification (OSNA) discriminates with great accuracy BC patients with negative or positive lymph nodes in comparison with the conventional OSNA cut-off of 5000 copies, contributing to better identify patients who really need an axillary node dissection.
- We have evaluated HER2 status in a series of BC, defined as low amplified or equivocal by in situ hybridization (ISH), using a more objective molecular assay (MLPA), which resulted a reliable and objective supporting test in identifying HER2 positive BC patients.
- The recent introduction of Next Generation Sequencing (NGS) for routine molecular diagnosis mainly of Non Small Cell Lung Cancer and Colorectal Carcinoma allowed us to detect clinically actionable genomic alterations quickly and reliably. The diagnostic output generated by the Oncomine Knowledge Reporter (OKR) software provided clinical oncologists with continuously updated and readily accessible information in accordance with approved guidelines for patients’ clinical management, and ongoing clinical trials for the potential enrollment of eligible patients.
- We have investigated the association between the expression of the glucose transporter GLUT1 in a series of FIGO high grade/stage serous ovarian carcinomas. The evidence that strong GLUT1 staining was inversely associated with circulating levels of fasting glucose may help to clarify the potential of biomarkers related to energy metabolism, in terms of prognosis definition and treatment assignment.
- We have contributed to evaluate the prognostic role of NF-Ya splicing isoform and Laminin A status in low grade endometrial cancer with high risk of progression.
Main International Collaborations (thymic epithelial tumours, male and female breast cancer, colon and ovarian cancer)
In the framework of international studies we have participated in the International Collaboration on Cancer Reporting (ICCR) initiative for the development of a dataset for TET reporting. Moreover, we have contributed to the new TNM staging of TET and of Lung cancer, by collaborating with UICC in the Staging and Prognostic Factors Committee (SPFC)
We have participated to a multicenter study (University of Leeds, UK) aimed to analyze the survival impact of 14 biomarkers (ERα, ERβ1, ERβ2, ERβ5, PR, AR, Bcl-2, HER2, p53, E-cadherin, Ki67, survivin, prolactin, FOXA1) in a large series of male breast cancer on tissue microarrays. FOXA1 and AR were both positively prognostic for survival, remaining upon multivariate analysis.
We have been involved in a study aimed to investigate the prognostic role of a class of small RNAs generated during the maturation process of tRNA tRNA-derived small RNAs (tsRNA) known to be deregulated during carcinogenesis, in colon, breast and ovarian cancer (The Ohio State University Comprehensive Cancer Center, USA).discipline