Ovarian cancer molecular pathology

Abstract

Ovarian cancer (OVC) is the fourth leading cause of cancer mortality among women in Europe and the United States. Its early detection is difficult due to the lack of specificity of clinical symptoms. Unfortunately, late diagnosis is a major contributor to the poor survival rates for OVC, which can be attributed to the lack of specific sets of markers. Aside from patients sharing a strong family history of ovarian and breast cancer, including the BRCA1 and BRCA2 tumor suppressor genes mutations, the most used biomarker is the Cancer-antigen 125 (CA-125). CA-125 has a sensitivity of 80 % and a specificity of 97 % in epithelial cancer (stage III or IV). However, its sensitivity is 30 % in stage I cancer, as its increase is linked to several physiological phenomena and benign situations. CA-125 is particularly useful for at-risk population diagnosis and to assess response to treatment. It is clear that alone, CA-125 is inadequate as a biomarker for OVC diagnosis. There is an unmet need to identify additional biomarkers. Novel and more sensitive proteomic strategies such as MALDI mass spectrometry imaging studies are well suited to identify better markers for both diagnosis and prognosis. In the present review, we will focus on such proteomic strategies in regards to OVC signaling pathways, OVC development and escape from the immune response.

HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer

“…In particular, the failure to detect this "silent killer" disease early results in tumor progression to an advanced stage, accompanied by metastasis. Although dissemination of most cancer cells requires migration within the vasculature, the exfoliated ovarian carcinoma cells may be transported throughout the peritoneal cavity to adjacent organs by normal peritoneal fluid; this lack of an anatomical barrier further accelerates metastasis (Longuespee et al 2012). It is almost impossible to render patients free of the disease with surgery due to this diffuse feature, and ∼70% of patients present with disease that has spread beyond the ovaries.…”

Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system

“…Non-detection of specific early symptoms together with the absence of reliable screening strategies often leads to diagnosing ovarian cancer only in advanced stages, resulting in poor overall survival. Moreover, despite multimodal treatment options, high incidences of relapses occur [24][25][26][27]. Although improvements in surgical management and advances in cytotoxic therapy have been accomplished in the past decades, the overall 5-year survival rate for women with advanced disease can be as low as 13 % [24,25,28,29].…”

HFIP Extraction Followed by 2D CTAB/SDS-PAGE Separation: A New Methodology for Protein Identification from Tissue Sections after MALDI Mass Spectrometry Profiling for Personalized Medicine Research

“…Recent transcriptomic experiments demonstrated an increased expression of lamins A and C in ovarian cancer (Prokocimer et al, 2009), which is in line with our results. Transgelin is a protein associated with the cell migration and adhesion phenomena (Longuespee et al, 2012b), and vinculin is associated with tumor progression. Chaperon proteins (HSP90 and GRP78) have also been characterized.…”