Expression of BAG-1 and PARP-1 in Precursor Lesions and Invasive Cervical Cancer Associated with Human Papillomavirus (HPV)

Hassumi‐Fukasawa, Marcela Kazue; Miranda-Camargo, Fabiana Alves; Zanetti, Bruna Riedo; Galano, Denise Faria; Ribeiro‐Silva, Alfredo; Soares, Edson García

doi:10.1007/s12253-012-9523-y

Cited by 28 publications

(16 citation statements)

References 26 publications

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“…Notably, the present study similarly demonstrated that PARP-1 expression levels were significantly increased in H. pylori infected gastric cancer cells. Regarding pathogenic infection, Hassumi-Fukasawa et al (51) demonstrated a significant positive association between PARP-1 expression levels and human papilloma virus positivity, in high-grade squamous intraepithelial lesions of the uterine cervix. Therefore, PARP-1 expression levels may be involved in host cell responses to pathogen infection.…”

Section: Discussionmentioning

confidence: 99%

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

Liu

Zhao

et al. 2016

Oncology Letters

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Poly (adenosine diphosphate-ribose) polymerase 1 (PARP-1) was previously demonstrated to be overexpressed in numerous malignant tumors and associated with invasiveness and poor prognosis. However, the expression of the PARP-1 protein in gastric cancer and its association with clinical outcomes requires further investigation. In the present study, the expression of PARP-1 in 564 gastric cancer tissues and 335 tumor-adjacent control tissues is investigated, using tissue microarray-based immunohistochemistry. PARP-1 expression levels were demonstrated to be significantly higher in gastric cancer tissue samples, as compared with control tissue samples. In gastric cancer, high PARP-1 expression levels were significantly associated with Helicobacter pylori (H. pylori) infection (P=0.032), decreased differentiation (P<0.001), increased depth of invasion (P=0.037), presence of lymphatic invasion (P<0.001), presence of lymph node metastasis (P<0.001), and advanced tumor-node-metastasis (TNM) stage (P=0.015). High PARP-1 expression levels were associated with a significantly shorter overall survival rate (P<0.001) and disease-free survival rate (P=0.001) in patients with gastric cancer, particularly a subset of patients with H. pylori infection or an advanced TNM stage. In addition, univariate analysis indicated that PARP-1 high expression levels were significantly associated with a poor prognosis in gastric cancer. These results suggest that PARP-1 expression may be involved in the progression and prognosis of gastric cancer, particularly H. pylori-positive or advanced-stage gastric cancer.

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Section: Discussionmentioning

confidence: 99%

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

Liu

Zhao

et al. 2016

Oncology Letters

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“…In contrast, PARP-1 was easily detected by immunohistochemistry in 86%, 77.5%, and 94% of patients with low-grade SIL (50 samples), high-grade SIL (HSIL, 50 samples), and invasive squamous cell carcinoma (SCC, 50 samples), respectively. 7 In the HSIL group, HPVpositive cells seem to express PARP-1 to a higher degree than HPV-negative cells. Moreover, in invasive cancer tissues, a significantly higher immunostaining of PARP-1 compared with HSIL was found (P = 0.001).…”

Section: Parp-1 Expression In Cervical Precancer and Cancermentioning

confidence: 89%

“…In a study by Hassumi-Fukasawa et al, 7 the immunohistochemical staining of normal cervical tissues revealed no PARP-1 expression or only light staining in the areas of the basal and parabasal layer cells of the ectocervix. In contrast, PARP-1 was easily detected by immunohistochemistry in 86%, 77.5%, and 94% of patients with low-grade SIL (50 samples), high-grade SIL (HSIL, 50 samples), and invasive squamous cell carcinoma (SCC, 50 samples), respectively.…”

Section: Parp-1 Expression In Cervical Precancer and Cancermentioning

confidence: 94%

“…Moreover, in invasive cancer tissues, a significantly higher immunostaining of PARP-1 compared with HSIL was found (P = 0.001). 7 Although the first article demonstrating that PARP activity was almost twice as high in cervical cancer cell nuclei compared with normal cervical cell nuclei was published more than 30 years ago, 8 the current knowledge regarding the expression and activity of PARPs in invasive cervical cancer still remains obscure. High levels of PARP-1 and its product PAR were found in cisplatin-resistant HeLa and other cancer cell lines compared with their cisplatin-sensitive counterparts, suggesting that PARP activity was implicated in cisplatin resistance and that the resistant cells were hyperdependent on PARP activity for survival.…”

Section: Parp-1 Expression In Cervical Precancer and Cancermentioning

confidence: 99%

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Poly(ADP-Ribose) Polymerase in Cervical Cancer Pathogenesis: Mechanism and Potential Role for PARP Inhibitors

Kotsopoulos¹,

Kucukmetin²,

Mukhopadhyay³

et al. 2016

Int J Gynecol Cancer

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Treatment options for disease recurrence of women treated for locally advanced and advanced cervical cancer are very limited-largely palliative chemotherapy. The low efficacy of the currently available drugs raises the need for new targeted agents. Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) have emerged as a promising class of chemotherapeutic agents in cancers associated with defects in DNA repair. Their therapeutic potential in cervical cancer is currently being evaluated in 3 ongoing clinical trials. Here we review the available information regarding all the aspects of PARP in cervical intraepithelial neoplasia and invasive cervical cancer, from expression and the mechanism of action to the role of the polymorphisms in the pathogenesis of the disease, as well as the potential of the inhibitors. We finally propose a new unifying theory regarding the role of PARPs in the development of cervical carcinomas.

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“…It has been reported that some viruses associate with the genesis of various benign disorders and some malignant tumours such as cervical cancer (26)(27)(28)(29). Although uterine cervix malignancy is reported to be the fifth most common cancer among Iranian females (30), in many other countries, cervical squamous cell carcinoma is the second most prevalent malignancy (31,32). For a long time, HPV infections have been considered one of the most important aetiological factors in the development of uterine cervix SCC.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Expression of Apoptosis Regulators in Squamous Cell Carcinoma of the Cervix and Their Association with Human Papillomavirus 16/18 Subtypes

Ayatollahi¹,

Sharifi²,

Sadeghian³

et al. 2014

Balkan Med J

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Squamous cell carcinoma (SCC) of the cervix is one of the most frequent female genital tract cancers, which causes a high level of malignancy-related mortality, affecting a large population worldwide. All of the effects of Human papilloma virus (HPV) infection, which is an important aetiological factor in the development of cervical carcinoma, remain to be clarified completely (1). Compared to studies focused on high risk HPVs in squamous cell carcinoma of the cervix, there are few studies about the mechanisms of carcinogenesis in cervical SCCs lacking HPV.There are about 40 subtypes of HPV affecting the genital tract, some of them have a high association with SCC of the cervix (2). Although more than 20 types of HPV have been found in these tumours, 4 types are responsible for more than 80% of cases (3, 4) and HPV 16 is the most frequent. HPV 16 and 18 are the most oncogenic and virulent types, and altogether are responsible for 70% of uterine cervix cancer (5, 6). Sexual intercourse is the main route of transmission of HPV infection; the frequency of HPV infection in different populations and countries varies widely (7). High risk HPVs, especially HPV 16 and 18, probably impose their early carcinogenesis effect by impairing the cell cycle through modulation of different genes' expression, including E6/E7 proteins (8). These early proteins, E6 and E7, bind and inactivate a tumoursuppressor gene product, p53, and the retinoblastoma tumoursuppressor protein, respectively. In cervical lesions caused by HPVs, the increased proliferation of suprabasal epithelial cells is attributed to the expression of the viral oncogenes, E6 and E7. E7 associates with Rb protein and other members of the pocket protein family, and disrupts the association Background: Human papillomavirus (HPV) infection is an important aetiological factor in squamous cell carcinoma (SCC) of the cervix. Limited studies have been focused on the differences between carcinogenesis of SCCs with and without HPV infection. Aims: The main goal of this study is to determine the expression of some of the apoptotic pathway regulators, including P53, Bax and Bcl2 in SCCs with and without high risk HPV 16/18 infection. Study Design: Cross sectional study. Methods: A total of 42 paraffin-embedded blocks with the histopathological diagnosis of invasive SCC with determined HPV 16/18 status were selected; half of them were HPV positive and the rest were negative. Afterwards, immunohistochemistry stained slides for p53, Bcl2 and Bax were evaluated with H-score, multiplicative and Additive Quick score by two pathologists; in cases of controversy about the results, the mean results were recorded. Results:Mean results and percentage of expression of our three markers were significantly higher in the HPV 16/18 infected group than in uninfected individuals: Respectively, the mean score for Bcl2, Bax and p53 staining according to H-scoring method was 68.5, 234, 106.4 in the HPV 16/18 infected group and 4.5, 218.8, 5.07 in the uninfected group; and the Multiplicative Quick ...

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Expression of BAG-1 and PARP-1 in Precursor Lesions and Invasive Cervical Cancer Associated with Human Papillomavirus (HPV)

Cited by 28 publications

References 26 publications

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

High PARP-1 expression is associated with tumor invasion and poor prognosis in gastric cancer

Poly(ADP-Ribose) Polymerase in Cervical Cancer Pathogenesis: Mechanism and Potential Role for PARP Inhibitors

Immunohistochemical Expression of Apoptosis Regulators in Squamous Cell Carcinoma of the Cervix and Their Association with Human Papillomavirus 16/18 Subtypes

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