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.

Rare stromal corneal dystrophic diseases in Oman: A clinical and histopathological analysis for accurate diagnosis.

INTRODUCTION: Corneal dystrophy (CD) encirclements a heterogeneous group of genetically determined corneal diseases. Many features still remain unknown. AIM: The purpose of this study was to highlight the clinical and the histopathological aspects of rare stromal CDs and to assess the clinical and the histopathological roles in their diagnosis. PATIENTS AND METHODS: This study incorporated 10 eyes of six patients, clinically diagnosed as follows: four patients with bilateral lattice stromal CD (8 eyes) and two patients, each one eye, one with macular and the other with granular-type CD. Histopathological examination with applications of many special stains was done in four eyes (4 patients) after penetrating keratoplasty. RESULTS: The histopathological examination was in concordance with the clinical diagnosis of three examined corneas and revealed first eye with lattice dystrophy, second eye with macular dystrophy, and third eye with granular dystrophy. The fourth examined cornea was not that in concordance with the clinical diagnosis of lattice CD as it showed mixed stromal CD patterns of granular, macular, and lattice types. CONCLUSION: Histopathological assessment of corneal dystrophy cases, subjected to keratoplasty is recommended to avoid missing cases with mixed stromal corneal dystrophy. Also, using low magnification slit lamp alone in the clinical assessment of the corneal opacity appeared to be limited mode and thus, the imaging corneal methods such confocal microscopy and high-definition optical coherence tomography are recommended for future cases especially in cases with unclassic query diagnosis.