Sections were counterstained with Mayer’s hematoxylin

jamha October 4, 2024 0 Comments

Sections were counterstained with Mayer’s hematoxylin. domain (EpEx) and release of its intracellular domain (Ep-ICD) which triggers oncogenic signaling and might correlate to tumor aggressiveness. This study aimed to explore the potential of Ep-ICD and EpEx RGD (Arg-Gly-Asp) Peptides to identify PCa that have poor prognosis. Methods Immunohistochemical analysis of Ep-ICD and EpEx was carried out in normal prostate tissues (n = 100), benign prostate hyperplasia (BPH, n = 83), and prostate cancer (n = 249) using domain specific antibodies. The expression of Ep-ICD and EpEx was correlated with clinico- pathological parameters and disease free survival (DFS). Results Reduced expression of nuclear Ep-ICD and membrane EpEx was observed in PCa in comparison with BPH and normal prostate tissues (p = 0.006, p 0.001 respectively). For patients who had PCa with Gleason Score less than 7, preserved nuclear Ep-ICD emerged as the most significant marker in RGD (Arg-Gly-Asp) Peptides multivariate analysis for prolonged DFS, where these patients did not have recurrence during follow up of up to 12 years (p = 0.001). Conclusion Reduced expression of nuclear Ep-ICD was associated with shorter disease free survival in patients with a Gleason Score less than 7 and may be useful Rabbit Polyclonal to CREB (phospho-Thr100) in identifying patients likely to have aggressive tumors with poor prognosis. Furthermore, nuclear Ep-ICD can differentiate between normal and prostate cancer tissues for ambiguous cases. Introduction Prostate cancer (PCa) is the second most common cancer in the world, with an estimated 900,000 cases and 258,000 deaths in 2008 [1]. The United States will have an estimated 239,000 new cases, and 29,700 deaths in 2013 alone [2]. The ideal treatment for PCa continues to be a challenge for oncologists worldwide. There are curative treatments for PCa however, these are associated with increased patient morbidity; some of these patients are over-treated while others are under-treated. The incidence of PCa continues to rise with increased use of the screening tool, prostate specific antigen (PSA) resulting in an increase in indolent tumors that are managed by active surveillance, where patients would get biopsied periodically to detect disease progression [3]. Management of PCa relies heavily on a variety of factors namely, physical examination, PSA level, Gleason score (GS), clinical stage, tumor extent, invasion and imaging. Even with these clinical factors, prognosis is hard to define. Usually the size of tumor and appearance under microscope would mandate the patients treatment; some patients with good prognosis get the same treatment as patients with poor prognosis leading to under- or over- treatment. Furthermore, some PCa cases have diagnostic uncertainty where the pathology reports state suspicious for cancer [4]. The patients with these diagnoses are usually sent for a repeat biopsy, causing more distress. Thus, there is an unmet need for newer and better diagnostic and prognostic markers for more effective disease management. Epithelial cell adhesion molecule (EpCAM) has been widely explored as an epithelial cancer antigen [5]. It is a glycosylated, 30- to 40-kDa type I membrane protein, expressed in several human epithelial tissues, and overexpressed in cancers as well as in progenitors and stem cells [5C9]. EpCAM is comprised of an extracellular domain (EpEx) with epidermal growth factor (EGF) and thyroglobulin repeat-like domains, a single transmembrane domain, and a short 26-amino acid intracellular domain called Ep-ICD. In normal cells, this full length EpCAM protein is sequestered in tight junctions and therefore less accessible to antibodies, whereas in cancer cells it is homogeneously distributed on the cancer cell surface and has been explored as a surface-binding site for therapeutic antibodies. EpCAM is expressed in majority of human epithelial cancers, including breast, colon, gastric, head and neck, prostate, pancreas, ovarian and lung cancer and is one of the most widely investigated protein for its diagnostic and therapeutic potential [10C13]. Increased EpCAM expression is a poor prognostic marker in breast and gall bladder cancers [14,15], while it is associated with favorable prognosis in colorectal and gastric cancers [16C19]. This paradoxical association of EpCAM expression with prognosis RGD (Arg-Gly-Asp) Peptides in different cancers may be explained by the functional studies of EpCAM biology.