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Although the very high locoregional recurrence rates reported with limited D0/D1 surgery can be reduced with extended D2 gastrectomy for operable gastric cancer, overall relapse and survival rates remain poor and can only be improved with adequate perioperative adjuvant treatment. However, despite intensive research, no regimen has been established as standard. Meta-analyses have demonstrated a marginal survival benefit with adjuvant chemotherapy. Two recent large randomized trials for operable gastric cancer, the MAGIC trial and the INT-0116 trial, provide evidence that some patients may benefit from perioperative chemotherapy and chemoradiation, respectively. However, while both trials suggest an overall survival benefit with adjuvant treatment, they don't provide the harm-benefit ratio for specific subsets of patients wih different extent of surgery (D1 or D2) and tumor stage (early [T1,2]/advanced [T3,4]). This lack of evidence complicates current therapeutic adjuvant decisions. Estimating the risk of local and distant recurrence (high, moderate or low) after D1 or D2 surgery in various tumor stages and the expected harm-benefit ratio, the authors provide useful information for decisions on adjuvant chemotherapy with or withour radiotherapy in individual patients. Research on newer cytotoxic and targeted agents may improve treatment efficacy. Simultaneously, advances with microarray-based gene-expression profiling signatures may improve individualized treatment decisions. However, the validation and translation of these genomic classifiers as biomarkers into a completed 'bench-to-bedside' cycle for tailoring treatment to individuals is a major challenge and limits inflated expectations.

Object Medulloblastoma (MB) is the most common malignant brain tumor in children. Heat shock proteins (HSPs) comprise a superfamily of proteins that serve as molecular chaperones and are overexpressed in a wide range of human cancers. The purpose of the present study was to investigate the expression of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt by multiplex bead array assay of MBs. The results of HSP and Akt expression were correlated with MB subtype; immunohistochemical expression of Ki-67 index, bcl-2, and p53; and patients' prognosis. Methods The authors retrospectively evaluated 25 children with MB who underwent surgery. Immunohistochemical analysis of Ki-67, p53, and bcl-2 expression was performed in all cases. By using multiplex bead array assay, a simultaneous detection of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt was performed. Results Medulloblastoma with extensive nodularity had significantly lower HSP27 (pSer15) expression (p = 0.039) but significantly higher HSP60 expression (p = 0.021) than classic MB. Large-cell MB had significantly higher HSP70 expression (p = 0.028) than classic MB. No significant difference was found between HSP27 (pSer82), HSP40, HSP90-α, Akt, or phospho-Akt expression and MB subtype. Large-cell MBs had significantly higher Ki-67 index compared with classic MBs (p = 0.033). When analyzing all MBs, there was a significant negative correlation between HSP27 (pSer15) and Ki-67 index (r = −0.475, p = 0.016); a significant positive correlation between HSP70 expression and Ki-67 index (r = 0.407, p = 0.043); and a significant positive correlation between HSP70 expression and bcl-2 index (r = 0.491, p = 0.023). Patients with large-cell MB had a worse survival than those with classic MB, but the difference did not reach statistical significance (p = 0.076). Conclusions A substantial expression of several HSPs in MB was observed. Given that HSPs represent an attractive strategy for anticancer therapy, further studies, involving larger series of patients, are obviously necessary to clarify the relationship of HSPs with tumor aggressiveness and prognosis.

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