Evaluation of the Expression EGFR, HER2/NEU and the End Effector ERK of the RAS/RAF/MAP Kinase Pathway in Prostatic Adenocarcinoma for a Possible Role as New Target Therapy.

The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector molecule (ERK) are important in the carcinogenesis of many tumors. The activation of these protooncogenes in prostate cancer is still under investigation. The aim of this work was to study EGFR, HER2- neu, inactive (non-phosphorylated) and active (phosphorylated) ERK expression in prostatic adenocarcinomas in correlation to the clinical and pathological parameters. METHODS: Immunohistochemistry- using tissue microarrays- for EGFR, HER2/neu, non-phosphorylated, and phosphor-ERK, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically. RESULTS: The prostatic tissue showed EGFR, HER2 neu, phosphorylated and non-phosphorylated ERK expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse).  There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated ERK and EGFR- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively). CONCLUSION: EGFR and HER2/neu may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated ERK (mostly weak to moderate) and phosphorylated ERK (mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-EGFR drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/ERK drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.

Clinicopathological Study of Breast Carcinoma Patients with Equivocal HER2 Immunohistochemical Status: Five-Year Experience from a Tertiary Care Center.

Background and objectives: Assessment of HER2 gene status has central role in the management of breast cancer patients. For determining HER2 status, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the most commonly used tests. Immunohistochemistry scores of 3+ and 1+ were considered as HER2 positive and negative, respectively. On the other hand, HER2 equivocal cases need further confirmation by FISH test assessment. This study aimed to identify the clinicopathological characteristics of patients with HER2 equivocal tumors served by Sultan Qaboos University Hospital (SQUH) in Muscat, Oman, with emphasis on treatment plans and disease outcome. Methods: This was a retrospective cross-sectional study, which involved all breast cancer female patients who were referred to SQUH from 2016 to 2020. It included a total of 108 patients who were diagnosed with HER2 (2+) breast cancer. Patients' data were analyzed in relation to the subsequent FISH status. Results: During the study period, data from 108 females with HER2 2+ were collected; among them, 22 (20%) were FISH positive, 64 (59%) FISH negative, 17 (16%) FISH borderline and five (5%) with no results. Regarding patients' characteristics, 91.2% of all subjects had invasive ductal carcinoma, 93.2% expressed estrogen receptors and 77.6% progesterone receptor. Age, postmenopausal histopathology, tumor grade, TNM staging, ER, PR, Ki67, LVSI, NLR, treatment and follow-up did not show significant association with different FISH results. Conclusions: The majority of HER2 equivocal breast cancer cases were FISH negative. In trastuzumab chemotherapy, an association between different FISH results was expected.