Giada Pattaro

Detection of Phosphorylated Insulin Receptor in Colorectal Adenoma and Adenocarcinoma: Implications for Prognosis and Clinical Outcome

Colorectal carcinoma remains among the most frequent causes of cancer death. Besides the well‐known genetic predisposition, a key role in colorectal adenoma and adenocarcinoma etio‐pathogenesis, mainly in sporadic cases, is played by definite risk factors, such as obesity, type 2 diabetes, insulin resistance, hyper‐insulinemia, and insulin therapy. These epidemiological data motivated us to determine, by means of immunohistochemistry, the amount of activated (phosphorylated) insulin receptor in archival samples from 22 colorectal adenoma and 117 adenocarcinoma patients, with the objective to estimate the role of this factor in colorectal epithelium transformation and cancer progression. Statistical analysis of the results clearly showed that positive staining for phosphorylated insulin receptor was significantly more frequent in adenomas than adenocarcinomas (P < 0.0001) and, within the adenocarcinoma cohort, it was more frequent in low‐grade tumors (P = 0.005). In adenomas, staining was exclusively cytoplasmic, while in adenocarcinomas it was cytoplasmic and/or nuclear (P < 0.0001). Interestingly, disease‐free survival in colorectal adenocarcinoma patients pointed out a significantly better prognosis for those bearing a positive staining for phosphorylated insulin receptor (P = 0.02). From these data, we can argue that activated insulin receptor plays a fundamental role at the early stages of tumorigenesis, where late stages could be characterized by a shift toward more active oncogenic drivers. Determining the amount of phosphorylated insulin receptor could thus represent a novel prognostic/predictive tool in colorectal adenocarcinoma patients. J. Cell. Physiol. 230: 562–567, 2015.

Integration of radioembolisation into multimodal treatment of liver-dominant metastatic colorectal cancer

Introduction: Radioembolisation (selective internal radiation therapy; SIRT), as part of a continuous strategy contributed to the improvement in response rates and median survival for unresectable metastatic colorectal cancer. Therefore, the role of SIRT in the different stages of treatment plan was investigated in this review. Areas covered: After a brief description of the principles of SIRT, the review focused on the clinical evidences of published trials on the current experience of radioembolisation and its role in both salvage setting and earlier lines of chemotherapy. Expert opinion: Evidence from Phase I studies and small Phase II/III randomised controlled trials has provided an early signal of the safety and improved overall survival, which can be achieved with radioembolisation and chemotherapy compared with chemotherapy (alone), due to an improved liver control. In the salvage setting, interesting results were observed in term of response, toxicity and median overall survival. Until the results of these early-line randomised trials will be available, radioembolisation could be considered either alone or combined with an appropriate chemotherapy regimen following failure of first- or second-line therapy.

Tumor Regression Grade After Neoadjuvant Chemoradiation and Surgery for Low Rectal Cancer Evaluated by Multiple Correspondence Analysis: Ten Years as Minimum Follow-up

Background: The role of Mandards tumor regression grade (TRG) classification is still controversial in defining the prognostic role of patients who have undergone neoadjuvant chemoradiation (CRT) and total mesorectal excision. The present study evaluated multiple correspondence analysis (MCA) as a tool to better cluster variables, including TRG, for a homogeneous prognosis. Patients and Methods: A total of 174 patients with a minimum follow‐up period of 10 years were stratified into 2 groups: group A (TRG 1–3) and group B (TRG 4–5) using Mandards classification. Overall survival and disease‐free survival were analyzed using univariate and multivariate analysis. Subsequently, MCA was used to analyze TRG plus the other prognostic variables. Results: The overall response to CRT was 55.7%, including 13.2% with a pathologic complete response. TRG group A correlated strictly with pN status (P = .0001) and had better overall and disease‐free survival than group B (85.1% and 75.6% vs. 71.1% and 67.3%; P = .06 and P = .04, respectively). The TRG 3 subset (about one third of our series) showed prognostically heterogeneous behavior. In addition to multivariate analysis, MCA separated TRG 1 and TRG 2 versus TRG 4 and TRG 5 well and also allocated TRG 3 patients close to the unfavorable prognostic variables. Conclusion: TRG classification should be used in all pathologic reports after neoadjuvant CRT and radical surgery to enrich the prognostic profile of patients with an intermediate risk of relapse and to identify patients eligible for more conservative treatment. Thus, MCA could provide added value. Micro‐Abstract: The tumor regression grade (TRG) role was investigated by multiple correspondence analysis (MCA) in 174 low rectal cancer patients undergone neoadjuvant chemoradiation and radical surgery, with a minimum follow‐up of 10 years. The TRG 1 and 2 showed better survival than TRG 4 and 5 subgroups. MCA allocated TRG 3 together with other prognostic variables better than multivariate analysis.