## 6 Discussion
A total of 96% of the tumors were positive for EGFR expression, 63% tested positive for activated EGFR, 76% were positive for activated Akt, and 96% were positive for activated ERK1/2. Importantly, the histology score for Akt and ERK1/2 activation correlated with the histology score for activated EGFR [71]. The obtained results justify considering the use of EGFR inhibitors in the treatment of NETs [71; 72]. In addition, directly inhibiting Akt and ERK1/2 could present further therapeutic options for the treatment of neuroendocrine tumors (NETs) in the future. Exploring these pathways may lead to the development of novel strategies that enhance the effectiveness of existing treatments and improve patient outcomes [72; 73]. There are studies aimed at determining the clinical significance of serum EGFR concentrations in patients with breast cancer (BC) [74; 75; 76; 77]. Serum EGFR concentrations were determined by ELISA. Baseline serum EGFR concentrations were significantly higher than in healthy controls (\(p<0.001\)). Other known clinical variables, including histological grade or disease stage, were not correlated. In BC patients, despite elevated serum EGFR concentrations, EGFR concentrations have no predictive value [78]. The obtained results suggest that EGFR is the most interesting among the selected proteins. In our study, we observed that EGFR concentrations in patients with neuroendocrine tumors were significantly higher (\(p<0.001\)) in the study group compared with the control. This is consistent with findings in the literature [25; 79; 80]. EGFR concentration depending on the location of the primary tumor has been noted. Significantly higher (\(p<0.001\)) EGFR concentration was found in GEP-NETs than in BP-NETs. EGFR kinase is frequently overexpressed in various cancers, including non-small cell lung cancer, metastatic colorectal cancer, glioblastoma multiforme, head and neck cancer, pancreatic cancer, and breast cancer [79]. Genetic alterations result in the overactivation of downstream pro-oncogenic signaling pathways, which can initiate a cascade of biological processes that are crucial for cancer cell proliferation [80]. Lung neuroendocrine tumors and gastroenter-pacreatic neuroendocrine tumors are distinct types of neuroendocrine tumors from different origins but have often been treated similarly. Despite sharing phenotypic characteristics and neuroendocrine marker expression, they differ in microenvironment, molecular mutations, and therapeutic responses. Recent research highlights genetic differences, the role of EGFR in carcinogenesis, the presence of transcription factors, and tumor immunogenicity [81]. There are no clear data to verify the differences observed for BP-NETs and GEP-NETs. It seems that they should be found in different molecular pathways. Also, it should be noted that the BP-NET group was smaller (N = 20), which suggests that further research is needed to confirm these findings and use this knowledge in clinical practice. A close-to-significant correlation was found between EGFR and chromogranin A (\(p<0.05\)). This is particularly interesting because chromogranin A is the most important general circulating tumor marker, being expressed in 80-90% of all patients with gastroenter-teropancreatic neuroendocrine tumors. Determining chromogranin A levels is also useful for staging, prognosis, and follow-up, as its serum concentration correlates with tumor mass [82]. This relationship indicates that EGFR may be a good future indicator that can be used in the evaluation of patients with neuroendocrine tumors, particularly GEP-NETs. Next, in our study, we found a significant negative correlation between EGFR and BMI, but only in the control group (\(p<0.05\)). These results suggest that body mass index (BMI) may have an effect on EGFR concentration. Although there are no data in the literature on the relationship between BMI and EGFR in NET patients, EGFR mutations are the most common oncogenic drivers in non-small-cell lung cancer (NSCLC) [83; 84; 85].