SHP-2 Expression Is a Positive Prognostic Biomarker in Non-Small-Cell Lung Carcinoma: Association with KRAS Mutation and Prolonged Survival.

Background/Objectives: Lung cancer tumors are the most frequent malignant tumors and the primary cause of cancer-related deaths. Despite the improvement in survival related to the implementation of immunotherapy, a significant proportion of patients fail to demonstrate satisfactory response. As a result, the need for new biomarkers, which will predict patient response, as well as for novel therapeutic targets, is urgent. SHP-2 is an intracellular signal transduction molecule, modifying signal transduction of numerous intracellular cascades, acting primarily as an oncogene. In this study we analyzed the expression pattern of SHP-2 in a cohort of non-small-cell lung cancer cases and attempted to correlate it with available clinicopathological parameters. Methods: We performed immunohistochemistry for SHP-2 detection in a cohort of 258 NSCLC cases. H-score was estimated and statistical analyses correlated it with survival and other clinicopathological and molecular parameters. Results: SHP-2 expression was observed in 60 cases (23.3%), with an H-score ranging from 150 to 300. Positive samples were distributed among the three major histological subtypes, without statistically significant differences. Statistical analysis revealed significant positive correlation of SHP-2 expression with smoking, PD-L1 levels, and KRAS mutations. Moreover, positive SHP-2 immunohistochemistry was associated with better clinical outcome in both the total cohort and in the group of patients who received immunotherapy. Finally, the simultaneous presence of SHP-2 expression and KRAS mutation was correlated with prolonged survival. Conclusions: Our findings indicate that SHP-2 could be a useful prognostic factor and a very reliable biomarker in predicting response to immune checkpoint inhibitors.