MSI2 is not correlated to clinic-pathological variables in oral cancer

• ¹ Department of Clinical and Experimental Medicine, University of Foggia, Italy

Aim. MSI2 is a RNA-editing protein. Recently some studies evaluated its role in different cancer types, in which its upregulation is linked to a worst prognosis and negative clinic-pathological characteristics. Nowadays no studies have been published about MSI2 in oral cancer, so no information are available about its role in this specific type of cancer. Aim of this study was, through immunohistochemistry on histologic samples, to evaluate the relations between MSI2 protein expression and its link to clinic-pathological features in oral squamous cell carcinoma (OSCC). Materials and Methods. A Tissue Microarray (TMA) was set up including 88 patients, in order to evaluate MSI2 expression. All the patients filled the informed consent. After that the paraffin blocks were cored and put in contact with Anti-MSI2 mouse monoclonal antibody (OTI2F10) from abcam. Immuno-histochemical staining was performed, by evidencing the presence of MSI2 in our OSCC samples. The observational quantification analysis was performed by an experienced pathologist according to a previous study published about MSI2 expression in cervical cancer (1): The degree of immunostaining was scored according to the proportion of positively stained tumor cells and the intensity of staining. The proportion of stained cells was evaluated and recorded as: 0, no cells staining; score of 1 when <10% of tumor cells showed positive staining; score 2 when ranged between 10–50% of tumor cells exhibiting positive staining; score 3, from 51 to 80% of tumor cells exhibiting positive staining; and score 4, >80% of tumor cells exhibiting positive staining. The intensity of staining was scored as 0, when staining cells were not detectable; score 1, with weak staining; score 2, positive staining and score 3, when strong staining appeared. A summarizing score was calculated as quickscore (QS) by multiplying the staining intensity score and the percentage of stained tumor cells. A QS of ≤4 was defined as low MSI2 expression, whereas a QS of >4 was defined as high MSI2 expression. Results. We explored how MSI2 expression could influence the survival of patients with OSCC and its clinic-pathological correlations. Through a Univariate and Multivariate Cox regression analysis, we explored how MSI2 correlated with prognosis. It seems that patients with higher levels of MSI2 showed a worst prognosis (p = 0,593 Hazard Ratio 1,578 95% C.I. = 0,297-8,391). The association of MSI2 expression and age, sex, grading and staging, found no statistically significant correlation, also. Discussion. OSCC counts more than 200.000 new cases per year in the world. For cancer development it’s well known that mutagenic events could influence not only the starting process, but accumulation of them, could drive towards a different evolution and prognosis. Thanks to an improvement of research technologies, nowadays we are able to study the influence of different events, which interacts with biological mechanisms. In particular, epigenetic events assumed a new role. In this view, different reactions drive towards particular changes in post-transcriptional pattern. Musashi-2 (MSI2) is a new highlighted RNA-binding protein which is nvolved in different activities. In our study MSI2 resulted in many cases to be not expressed at immunohistochemistry analysis. Our results, which show no statistically significant correlation, could be justified by different mechanisms in which this protein is involved. In some cancer types it’s reported that traslocation and deregulation could be important factor in cancer initiation and progression (2). Some studies reported how this protein interacts with cell-cycle cells, above all in esophageal squamous cell carcinoma is reported that is linked to a Wnt/B-catenin pathway (3). Nowadays insufficient data are reported for OSCC. In particular, MSI2 could not be useful as a biomarker in prognosis or clinic-pathological variables. On the other side, MSI2 could play different roles in genetic changes or protein function that could only be explored by bimolecular analysis. For such reason, further studies are needed in order to explore MSI2 function is OSCC.