Background A relationship between the EGFR signaling pathway expression in skin and the use of targeted cancer therapies has been previously demonstrated. Consistent evidence to support the use of skin biopsies as a surrogate for therapeutic evaluation is needed. The purpose of this study was to establish the relationship between the expression of EGFR signaling pathway markers in skin samples from EGFR ‐mutated metastatic lung adenocarcinoma patients and their response to tyrosine kinase inhibitors. Methods This was a prospective single blind analysis of 35 skin biopsies from 31 patients with confirmed advanced EGFR ‐mutated lung adenocarcinoma. Immunohistochemistry was performed: EGFR, p27, Ki67, STAT3 and MAPK, as well as H&E histopathological analysis, in order to determine their treatment response to tyrosine kinase inhibitors. Results EGFR, Ki67, STAT3, stratum corneum thickness (number of layers and millimeters) from skin samples had a statistical correlation with an adequate treatment response ( P = 0.025, 0.015, 0.017, 0.041, 0.039 respectively). EGFR, p27 and number of layers of the stratum corneum were related to a better median progression‐free survival ( P = 0.025 and P = 0.030). Conclusions The relationship between EGFR pathway inhibition in the skin and oncological outcomes obtained explains the parallel biological effects of tyrosine kinase inhibitors. We hope that our work incites future research to help validate and assess the use of these markers as potential prognostic and predictive factors.
e21544 Background: A relationship between EGFR signaling pathway expression in skin and the use of targeted cancer therapies has been consistently demonstrated. Nonetheless, consistent evidence to support the use of skin biopsies as a surrogate for therapeutic evaluation. Methods: The present study is a prospective single-blind analysis of skin biopsies of patients with confirmed advanced EGFR mutated lung adenocarcinoma. Immunohistochemistry was performed with EGFR, p27, Ki67, STAT3, and MAPK, as well as an H&E histopathological analysis, looking for their relationship with the response to treatment with tyrosine kinase inhibitors. ROC curve analysis was used to determine the cutoff value for each biomarker selected dichotomizing the response to treatment as mentioned in the tissue samples section (adequate response or no response). Kaplan Meier analysis for progression-free survival was performed. Results: From the 35 biopsies obtained, 21 (60%) of the patients were women and 14 (40%) men; the mean age of participants was 60.6±11.7 years. Twelve patients (34.3%) were at the pre-treatment group, 12 (34.3%) had an adequate response to treatment and 11 (31.4%) were at the no response to treatment group. The median progression-free survival was 9 months. The next biomarkers were significantly related to an adequate response to treatment by using a bivariate correlation test: EGFR (p = 0.025), Ki67 (p = 0.015), STAT3 (p = 0.017), stratum corneum thickness (p = 0.039) and the number of layers of the stratum corneum(p = 0.041). A better median of progression-free survival was obtained on those with a value above of the cutoff preestablished of EGFR (21 months versus 7 months, 95% CI 0-46 versus 4.23-9.77, p = 0.025) and number of layers of the stratum corneum (21 months versus 8 months, 95% CI 0-43.81 versus 6.72-9.28, p = 0.030), however, for p27 a better median of progression-free survival was shown in those with a value below the cutoff before mentioned (21 months versus 8 months, 95% CI 8.17-33.83 versus 6.87-9.13, p = 0.031). Conclusions: We found a relationship between EGFR, Ki67, STAT3, stratum corneum, number of layers of stratum corneum, with the response to treatment, and better progression-free survival for high expression EGFR, number of layers of the stratum corneum and low expression for p27. The present study should incite to perform a further investigation to validate these markers as potential prognostic and predictive factors.
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