scholarly journals Detection of Human Cytomegalovirus in Patients with Epithelial Ovarian Cancer and its Impacts on Survival

2020 ◽  
Author(s):  
Min Yin ◽  
Aiping Chen ◽  
Fei Zhao ◽  
Xuechao Ji ◽  
Chuan Li ◽  
...  

Abstract Background: The cause of epithelial ovarian cancer(EOC) is not elucidated. Viral infection may induce chronic inflammatory infection and play a role in the pathogenesis of cancers. Some viruses are considered to be oncomodulatory, modulating cellular pathways such as cell proliferation, tumor progression, vascular disease development, and immune evasion. Human cytomegalovirus (HCMV) has been detected in several types of cancers including ovarian cancer. However, the role of HCMV in ovarian carcinogenesis remains controversial. Objective: To investigate the potential role of HCMV infection in EOC, we evaluated the prevalence of HCMV proteins in EOC tissue and its impacts on patients’ survival. Methods: Formalin-fixed, paraffin-embedded tissues from 66 patients with EOC and 30 patients with benign ovarian cystadenoma were studied. Specimens were detected for expression of HCMV immediate-early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Results: HCMV-IE protein expression was detected in 82% of EOC and 36% of benign tumors; pp65 was detected in 97% of EOC and 63% of benign tumors. Extensive expression of HCMV-IE protein was associated with higher stage of EOC. Reactivation of latent HCMV within the tumor at interval debulking surery may be induced by neoadjuvant chemotherapy before surgery. Extensive HCMV-IE expression was associated with shorter median overall survival than focal or negative expression (39 versus 41 months, P=0.03). Multivariate analysis indicated that HCMV-IE expression was an independent prognostic factor for overall survival (P = 0.034). Conclusions: This study demonstrate a high prevalence of HCMV proteins in tissue sections from patients with EOC. HCMV infection can be potential risk factor for EOC development. Extensive HCMV-IE expression indicated a poor prognosis. The relationship between HCMV and clinical outcomes highlight the need for further researches on the oncomodulatory of HCMV in ovarian cancer. Keywords: Epithelial ovarian cancer, Human cytomegalovirus, Viral carcinogenesis, Survival

2020 ◽  
Author(s):  
Min Yin ◽  
Aiping Chen ◽  
Fei Zhao ◽  
Xuechao Ji ◽  
Chuan Li ◽  
...  

Abstract Background: The cause of epithelial ovarian cancer(EOC) is not elucidated. Viral infection may induce chronic inflammatory infection and play a role in the pathogenesis of cancers. Some viruses are considered to be oncomodulatory, modulating cellular pathways such as cell proliferation, tumor progression, vascular disease development, and immune evasion. Human cytomegalovirus (HCMV) has been detected in several types of cancers including ovarian cancer. However, the role of HCMV in ovarian carcinogenesis remains controversial.Objective: To investigate the potential role of HCMV infection in EOC, we evaluated the prevalence of HCMV proteins in EOC tissue and its impacts on patients’ survival.Methods: Formalin-fixed paraffin-embedded tissues from 66 patients with EOC and 30 patients with benign ovarian cystadenoma were studied. Specimens were analyzed for expression of HCMV immediate early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Results: HCMV-IE protein expression was detected in 82% of EOC and 36% of benign tumors; pp65 was detected in 97% of EOC and 63% of benign tumors. Extensive HCMV-IE protein expression was associated with higher stage of EOC. Reactivation of latent HCMV within the tumor at interval debulking surgery may be induced by neoadjuvant chemotherapy before surgery. Extensive HCMV-IE expression was associated with shorter median overall survival than focal or negative expression (39 versus 41 months, P=0.03). Multivariate analysis indicated that HCMV-IE expression was an independent prognostic factor for overall survival (P = 0.034). Conclusions: This study demonstrate a high prevalence of HCMV proteins in tissue sections from patients with EOC. HCMV infection can be potential risk factor for EOC development. Extensive HCMV-IE expression indicated a poor prognosis. The relationship between HCMV and clinical outcomes highlight the need for further researches on the oncomodulatory role of HCMV in ovarian cancer.


2020 ◽  
Author(s):  
Min Yin ◽  
Aiping Chen ◽  
Fei Zhao ◽  
Xuechao Ji ◽  
Chuan Li ◽  
...  

Abstract Background: The cause of epithelial ovarian cancer(EOC) is not elucidated. It has been proved that infectious agents could contribute to ovarian carcinogenesis. Human cytomegalovirus (HCMV) has been detected in several types of tumors. Objective: To investigate the potential role of HCMV infection in EOC, we evaluated the prevalence of HCMV proteins in EOC tissue sections and its impacts on patients’ survival. Methods: Formalin-fixed, paraffin-embedded tissues from 66 patients with EOC and 30 patients with benign ovarian cystadenoma were studied. Specimens were detected for expression of HCMV immediate-early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Results: HCMV-IE protein expression was detected in 82% of EOC and 36% of benign tumors; pp65 was detected in 97% of EOC and 63% of benign tumors. Extensive expression of HCMV-IE protein was associated with higher stage of EOC. Reactivation of latent HCMV within the tumor at interval debulking surery may be induced by neoadjuvant chemotherapy before surgery. Extensive HCMV-IE expression was associated with shorter median overall survival than focal or negative expression (39 versus 41 months, P = 0.03). Conclusions: This study demonstrate a high prevalence of HCMV proteins in tissue sections from patients with EOC. HCMV infections can be potential risks for EOC development. The relationship between HCMV and clinical outcomes highlight the need for further researches on the oncomodulatory role of HCMV in ovarian cancer.


2012 ◽  
Vol 22 (6) ◽  
pp. 987-992 ◽  
Author(s):  
Augusto Pereira ◽  
Tirso Pérez-Medina ◽  
Javier F. Magrina ◽  
Paul M. Magtibay ◽  
Isabel Millan ◽  
...  

ObjectiveTo evaluate the therapeutic role of pelvic and aortic lymphadenectomy in patients with epithelial ovarian cancer (EOC) and positive nodes (stages IIIC and IV).MethodsRetrospective chart review. Data from all consecutive patients with EOC and positive retroperitoneal lymph nodes (stage IIIC and IV) in Mayo Clinic from 1996 to 2000 were included. To evaluate the impact of nodal metastases, the extent of lymphadenectomy was compared according to the number of nodes removed and positive nodes resected. Multivariable Cox regression and Kaplan-Meier survival curves were used for analysis.ResultsThe median number of nodes removed was 31 (pelvic, 21.5, and aortic, 10), and the median number of positive nodes was 5. The 5-year overall survival was 44.8%. On multivariate analysis, only the extent of peritoneal metastases before surgery was a significant factor for survival (P = 0.001 for stage IIIC and P = 0.004 for stage IV). Analysis of 83 patients with advanced peritoneal disease more than 2 cm demonstrated before debulking, removal of more than 40 lymph nodes was a significant prognostic factor for overall survival (hazard ratio, 0.52; P = 0.032; 95% confidence interval, 0.29–0.35). In 29 patients with advanced peritoneal disease and no residual disease after debulking, removal of more than 10 positive was a factor for survival.ConclusionsThere was a survival benefit in patients with EOC with advanced peritoneal disease more than 2 cm before debulking when more than 40 lymph nodes were removed. There was an additional survival benefit in those patients with no residual disease after debulking when more than 10 positive nodes were removed.


Oncotarget ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1085-1095 ◽  
Author(s):  
Patricia Ferreira ◽  
Rosimeire Aparecida Roela ◽  
Rossana Veronica Mendoza Lopez ◽  
Maria Del Pilar Estevez-Diz

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Zhe Wang ◽  
Jun Cai ◽  
Mingming Zhang ◽  
Xiaojing Wang ◽  
Hongjie Chi ◽  
...  

Previous studies showed that human cytomegalovirus (HCMV) is associated with atherosclerosis. However, local vascular atherosclerosis related HCMV infection and protein expression remain unclear. This study aimed to assess the relationship between HCMV infection and atherosclerosis. Formalin-fixed, paraffin-embedded peripheral artery specimens were obtained from 15 patients with atherosclerosis undergoing vascular surgery from 2008 to 2010 at Zhongnan Hospital, Wuhan University. Pathological analyses were carried out after hematoxylin and eosin (H&E) and Masson trichrome staining. In situ hybridization and immunohistochemistry with two different monoclonal antibodies were employed to detect HCMV nucleic acids and proteins, respectively. H&E and Masson trichrome staining showed homogeneous extracellular matrix in femoral artery, while smooth muscle fibers were interlaced with collagen fibers; in carotid artery, inflammatory cell infiltration, foam cell vascular change, cholesterol crystals, and layered collagen fibers were observed. In situ hybridization showed no expression of HCMV nucleic acids in all 15 cases. Immunohistochemical staining for protein immediate-early protein (IE1 72) was negative in all cases, while phosphoprotein 65 (pp65) expression was detected in 14 cases. A high rate of positive pp65 signals was found in patients with atherosclerosis, suggesting that local HCMV infection may be associated with the pathogenesis of atherosclerosis. Further studies on this relationship are warranted.


2011 ◽  
Vol 21 (9) ◽  
pp. 1592-1600 ◽  
Author(s):  
Karina Dahl Steffensen ◽  
Marianne Waldstrøm ◽  
Anni Grove ◽  
Bente Lund ◽  
Niels Pallisgård ◽  
...  

ObjectiveAn increasing body of evidence has suggested that epithelial ovarian cancer (EOC) patients can broadly be divided into 2 groups on the basis of histopathologic parameters and molecular profiles. Type 1 tumors are slow-growing tumors with inherent mutations such as KRAS or BRAF mutations, whereas type 2 tumors are more rapidly growing tumors of which many contain TP53 mutations. In the present study, we performed a comprehensive study in a large Danish material to evaluate the clinical importance.Materials and MethodsA total of 512 tissue samples were included (430 EOCs, 34 borderline, 28 benign tumors, and 20 normal ovaries). KRAS mutations (codon 12/13) and BRAF codon 600 mutations were analyzed from formalin-fixed paraffin-embedded tissue by ARMS qPCR. p53 expression was examined by immunohistochemistry.ResultsOf the EOC patients, 25% had histopathologically classified type 1 tumors, and of these, 44% were either KRAS or BRAF mutated. Of patients with histopathologic type 2 tumors, 66% showed p53 protein overexpression, whereas 4 (1.5%) patients contained a KRAS mutation. In a univariate survival analysis, a large difference in survival was seen between patients with type 1 and type 2 tumors. Patients with type histologic 2 tumors had significantly worse survival compared with patients with type 1 tumors (P< 10−5). International Federation of Gynecology and Obstetrics (FIGO) stage, tumor grade, residual tumor, and KRAS/BRAF mutation were independent predictors of overall survival in the multivariate analysis. Patients with KRAS/BRAF mutated carcinomas showed independent decreased overall survival with a hazard ratio of 2.01 (95% confidence interval, 1.13–3.57;P= 0.018).ConclusionsKRAS/BRAF mutations are with very few exceptions constrained to patients with histopathologic type 1 tumors, whereas p53 overexpression is very frequent in type 2 tumors. KRAS/BRAF mutations had independent prognostic importance. The classification presented here should have a major therapeutic implication and serve as a hallmark of future clinical trials.


Author(s):  
Andrijono ◽  
Heru Prasetyo ◽  
Eka R Gunardi ◽  
Gatot Purwoto ◽  
Hariyono Winarto

Objective: To determine whether thrombocytosis is a prognostic factor for epithelial ovarian cancer and its relationship with 3-year overall survival in epithelial ovarian cancer patients.Methods: This study is a retrospective cohort study using medical record of patients with epithelial ovarian cancer registered in cancer registry of Oncology Division in Obstetrics and Gynecology Department, Dr. Cipto Mangunkusumo National General Hospital from January 2014 - July 2016. Data were collected when subjects were first until diseases outcomes identified in 3 years.Results: : Out of 220 subjects, 132 (60%) were patients with advanced stage epithelial ovarian cancer (stage II/III/IV). 94 (42.7%) subjects had thrombocytosis. Patients with advanced stage of disease had higher risk of having thrombocytosis than the ones with earlier stage (p=0.005; OR=2.329). Correlation between thrombocytosis and 3-year overall survival was known to be insignificant (p=0.555). There was shorter mean time survival between patients with thrombocytosis and the ones without but the there was no significant difference in hazard ratio between the two groups (p  = 0.399).Conclusion :Thrombocytosis is not a prognostic factor in patients with epithelial ovarian cancer. There is also no significant difference of 3-year overall survival between patients with or without thrombocytosis.Keywords: epithelial ovarian carcinoma, prognosis,  thrombocytosis.   Abstrak Tujuan: Membuktikan bahwa trombositosis sebagai faktor prognosis kesintasan pada pasien kanker ovarium jenis epitelial dan hubungannya terhadap kesintasan 3 tahun pasien kanker ovarium  jenis epitelial.Metode: Penelitian ini merupakan studi kohort retrospektif menggunakan data rekam medis pasien kanker ovarium epitelial yang terdaftar pada cancer registry Departemen Obstetri dan Ginekologi Divisi Onkologi Rumah Sakit Cipto Mangunkusumo pada tahun Januari 2014-Juli 2016. Pengamatan dilakukan saat subjek pertama kali didiagnosis akhir pengamatan selama 3 tahun.Hasil: Didapatkan 220 subjek penelitian yang merupakan populasi terjangkau dan memenuhi kriteria inklusi dan eksklusi. Dari 220 subjek penelitian, 132 (60%) dari 220 subjek penelitian merupakan pasien dengan kanker ovarium stadium lanjut (Stadium II/III/IV). Trombositosis didapatkan pada 94 orang subjek penelitian (42,7%). Pasien dengan kanker stadium lanjut memiliki risiko trombositosis yang lebih tinggi dibandingkan subjek pada stadium awal (p=0,005;OR=2,329). Trombositosis secara statistik tidak bermakna pada kesintasan 3 tahun (p=0,555). Terdapat mean time survival yang lebih rendah pada pasien dengan trombositosis tetapi tidak ada perbedaan hazard ratio yang bermakna antara subjek dengan atau tanpa trombositosis (p=0,399).Kesimpulan : Trombositosis bukan merupakan faktor prognostik pada pasien kanker ovarium jenis epitelial dan tidak terdapat hubungan antara trombositosis dan 3 tahun pada pasien dengan kanker ovarium jenis epithelial.Kata kunci: karsinoma ovarium epithelial,  prognosis, trombositosis


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