Reelin is a glycoprotein that plays a critical role in the regulation of neuronal migration during brain development and, since reelin has a role in the control of cell migration, it might represents an important factor in cancer pathology. In this study, 66 surgical specimens of prostate cancer were analyzed for reelin expression by immunohistochemical method. The reelin expression was correlated with Gleason score and individual Gleason patterns. Reelin expression was found in 39% prostate cancers. Stromal tissues, normal epithelial cells and prostate intraepithelial neoplasia (PIN) of any grade around and distant from cancer were always negative for reelin. Reelin was found in malignant prostatic epithelial glands of 50% cases Gleason score 10, 52% Gleason score 9, 56% Gleason score 8, 18% Gleason score 7, while no sample of prostate cancers with Gleason score 6 showed reelin expression (P ¼ 0,005). As reelin staining is frequently found in high Gleason score prostate cancers, we explored whether reelin expression is influenced by single Gleason patterns. While Gleason 3 pattern did not show reelin immunoreactivity, reelin expression was found in 35% Gleason 4 patterns and 45% Gleason 5 patterns (Po0.001). Our results demonstrated for the first time that reelin is expressed in prostate cancer and not in benign prostate tissue and its expression occurs in higher Gleason score and correlates significantly with increasing of single Gleason patterns. This suggests reelin may behave as a specific histological marker and may represent a useful biomarker to predict aggressive phenotypic behavior of prostatic cancer cells.

Literature on the role of human papillomavirus (HPV) in head and neck cancer (HNC) in Italy is limited, especially for non-oropharyngeal tumours. Within the context of the HPV-AHEAD study, we aimed to assess the prognostic value of different tests or test algorithms judging HPV carcinogenicity in HNC and factors related to HPV positivity at the European Institute of Oncology. We conducted a retrospective cohort study (2000–2010) on a total of 696 primary HNC patients. Formalin-fixed, paraffin-embedded cancer tissues were studied. All HPV-DNA-positive and a random sample of HPV-DNA-negative cases were subjected to HPV-E6*I mRNA detection and p16INK4a staining. Multivariate models were used to assess for factors associated with HPV positivity and proportional hazards for survival and recurrence. The percentage of HPV-driven cases (considering HPV-E6*I mRNA positivity) was 1.8, 2.2, and 40.4% for oral cavity (OC), laryngeal (LC), and oropharyngeal (OPC) cases, respectively. The estimates were similar for HPV-DNA/p16INK4a double positivity. Being a non-smoker or former smoker or diagnosed at more recent calendar periods were associated with HPV-E6*I mRNA positivity only in OPC. Being younger was associated with HPV-E6*I mRNA positivity in LC. HPV-driven OPC, but not HPV-driven OC and LC, showed better 5 year overall and disease-free survival. Our data show that HPV prevalence in OPC was much higher than in OC and LC and observed to increase in most recent years. Moreover, HPV positivity conferred better prognosis only in OPC. Novel insights on the role of HPV in HNC in Italy are provided, with possible implications in the clinical management of these patients.

In an era of personalized treatment, there is a great interest in identifying factors which might predict patient response to radiotherapy (RT). The role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) remains still controversial. We performed a retrospective analysis on the prognostic value of EGFR in HNSCC patients treated with surgery and postoperative RT through a semiquantitative immunohistochemical analysis of EGFR membrane expression. We retrospectively analyzed 65 HNSCC patients treated in our Institute from 1997 to 2003 who underwent adjuvant RT after surgery. Median follow-up was 43.5 months (range 0.2-173 months). None of these patients were treated with postoperative concomitant chemotherapy. Tumor samples were obtained from surgical specimens. Membrane features (intensity, extension) of EGFR expression were evaluated, and a statistical analysis (univariate and multivariate) was conducted to correlate these parameters with overall survival (OS) and disease-free survival (DFS). Patients with an intense and complete labeling of EGFR presented worse OS and DFS compared with groups obtained by all other possible combination, and the difference was borderline statistically significant (P = 0.08 for OS and P = 0.006 for DFS). Moreover, a stratification of patients was performed considering EGFR expression on the tumor tissue and classifying its distribution as "homogeneous" or "heterogeneous." We found that patients showing an "heterogeneous" EGFR expression distribution had worse OS and DFS compared to the "homogeneous" group of patients. Based on our results, EGFR expression, especially referring to membrane features (semiquantitative analysis), might have a prognostic value for OS and DFS in locally advanced HNSCC treated with surgery and adjuvant RT. Prospective trials could be useful to confirm the prognostic role of EGFR expression and also to assess a predictive role to select that might benefit from more aggressive treatments.

To investigate the role of the altered activation of the immune system in the prognosis of patients affected by laryngeal squamous cell carcinoma (LSCC). We analyzed 56 patients with advanced LSCC divided into two groups according to their prognosis: the first group relapsed within 24 months after treatment, the second group had no evidence of disease at 2 years. The presence of stromal tumor infiltrating lymphocytes (TILs) at the tumor-host border was investigated. In 43 patients we evaluated the expression of 395 genes related to immune system activation through a next generation sequencing panel. Priority-LASSO models and clustering analyses were integrated with multivariate Cox proportional hazard modeling to identify independent genes associated with relapse and estimate hazard ratios in relation to gene expression and TILs. TILs and the expression of genes related with immune system activation (FCGR1A, IFNA17, FCRLA, NCR3, KREMEN1, CD14, CD3G, CD19, CD20 and CD79A) were significantly associated with prognostic factors or disease specific survival. In patients with lymph node metastases and advanced T stage (pT4), the expression of other genes was altered. Low TILs count was highly associated with relapse within 2 years (p < 0.001). Low TILs and altered expression of specific genes associated with tumor-immune systems interactions emerged as independent risk factors, associated to poor prognosis and relapse within 2 years in advanced LSCC. Evaluation of patients’ immune profile could be useful for prognosis and future therapeutic approaches towards personalized therapy.

No abstract