Cervical cancer is among the most commonly diagnosed cancer in women, supporting the need for identification of novel prognostic and predictive biomarkers to predict the risk of developing of this malignancy or predict the prognosis of patients. Against this background, the activation of the Wingless-type (Wnt)/β-catenin pathway has been suggested as the main dysregulated pathways, which is involved in the multistep process of cervical carcinogenesis, suggesting its value as a potential biomarker or therapeutic target. The aim of current review is to give an overview about the potential application of WNT pathway and its value which is differentially expressed in cervical cancer versus non-tumorigenic tissue as biomarker for risk stratification and predict the prognosis of patients with cervical cancer. J. Cell. Biochem. 118: 3028-3033, 2017. © 2017 Wiley Periodicals, Inc.
Cervical cancer (CC) is the third most common malignancy in women globally, and persistent infection with the oncogenic human papillomaviruses (HPV) is recognized as the major risk factor. The pathogenesis of CC relies on the interplay between the tumorigenic properties of the HPV and host factors. Host-related genetic factors, including the presence of susceptibility loci for cervix tumor is substantial importance. Preclinical and genome-wide association studies (GWAS) have reported the associations of genetic variations in several susceptibility loci for the development of cervical cancer. However, many of these reports are inconsistent. In this review, we discuss the findings to date of candidate gene association studies, and GWAS in cervical cancer. The associations between these genetic variations with response to chemotherapy are also discussed.
Aberrant activation of the HGF/c-Met signalling pathway is reported to be associated with cell proliferation, progression, and metastasis features of several tumor types, including cervical cancer, suggesting that it may be of potential value as a novel therapeutic target. Furthermore, HPV-positive patients had a higher serum level of HGF or c-Met protein, compared with HPV-negative patients. c-Met or HGF overexpression in lesions of cervical cancer is reported to be related to a poorer prognosis, and hence this may be of value as a prognostic and predictive biomarker. Several approaches have been developed for targeting HGF and/or c-Met. One of these is crizotinib (a dual c-Met/ALK inhibitor). This has been approved by FDA for the treatment of lung-cancer. Further investigations are required to evaluate and optimize the use of c-Met inhibitors in cervical cancer or parallel targeting signalling pathway associated/activated via MET/HGF pathway. The main aim of current review was to give an overview of the potential of the c-Met/HGF pathway as a prognostic, or predictive biomarker in cervical cancer.
BackgroundFinding a tumor marker to predict the aggressive behavior of molar pregnancy in early stages has yet been a topic for studies.ObjectivesIn this survey we planned to study patients with molar pregnancy to 1) assess the p53 and c-erbB-2 expression in trophoblastic tissue, 2) to study the relationship between their expression intensity and progression of a molar pregnancy to gestational trophoblastic neoplasia, and 3) to determine a cut off value for the amount of p53 and c-erbB-2 expression which might correlate with aggressive behavior of molar pregnancy.Patients and MethodsIn a prospective cross sectional study by using a high accuracy technique EnVision Tm system for immunohistochemistry staining of molar pregnancy samples, we evaluated p53 and c-erbB-2 expression in cytotrophoblast and syncytiotrophoblast and the correlation of their expression with progression of molar pregnancy to gestational trophoblastic neoplasia (GTN). Normal prostatic tissue and Breast cancer tissue were used as positive controls.ResultsWe studied 28 patients with simple molar pregnancy (SMP) and 30 with GTN. Cytotrophobalst had significantly higher expression of p53 and c-erbB-2 and syncytiotrophoblast had greater expression of p53 in GTN group as compared to SMP group. The cut off values for percentage of p53 positive immunostained cytotrophoblast and syncytiotrophoblast were 5.5% and 2.5%. In c-erbB-2 positive membranous stained cytotrophoblast the cut off was 12.5%.ConclusionsOur data suggests that over expression of p53 and c-erbB-2 is associated with malignant progression of molar pregnancy. We encountered that high expression of p53 and c-erbB-2 in trophoblastic cells could predict gestational trophoblastic neoplasia during the early stages.
Coronavirus (COVID-19) infection is a new major concern and a global emergency in almost all countries worldwide; due to the higher sensibility of cancer patients, they are more susceptible to severe and fatal infections, being nearly 10 times more likely than in healthy individuals infected with this virus. Although the aggressive nature of a cancer is a matter of concern, our exact role as oncologists in this time of restricted resources is not fully clarified. Regarding some consensus recommendation for postponing surgery, there is still an essential need for a single approved protocol regarding each type of malignancy. Iran, as one of the first involved countries in this crisis in Asia, which also has a high prevalence of gynecological malignancies, will certainly require an individualized decision-making schedule based on the most accepted global consensus opinion. Considering our restricted health system resources, herein we tried to introduce a logical gynecologic cancer management protocol based on the stage and survival expectancy of each tumor, along with reviewing all recent recommendations. The limited statistics published in this short period of time have obliged us to mainly focus on expert opinions, and the individualized clinical judgments should be agreed upon by multidisciplinary tumor board consensus. In conclusion, the COVID-19 pandemic overshadows all aspects of medicine, and decision making in gynecological oncology patients requires precise and appropriate judgment based on the available local resources.
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