Immunohistochemical Expression of Cyclin D1, p16Ink4a, p21WAF1, and Ki-67 Correlates With the Severity of Cervical Neoplasia

Portari, Elyzabeth Avvad; Russomano, Fábio Bastos; Camargo, Maria José de; Gayer, Carlos R. Machado; Guillobel, Heloísa Carneiro da Rocha; Santos-Rebouças, Cíntia Barros; Macedo, Jacyara Maria Brito

doi:10.1097/pgp.0b013e31826f5cf6

Cited by 28 publications

(25 citation statements)

References 33 publications

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“…CDKN1A was found to be hypermethylated in less than 10% of cervical cancer samples [31]. This is consistent with the reports of high levels of p21 in cervical cancer samples, which was also shown to be associated with the progression of lesions in several studies [23,24,86,87].…”

Section: Cell Cycle Regulation and Dna Repairsupporting

confidence: 86%

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Cardoso

Castelletti

Lima-Filho

et al. 2017

Mutation Research/Reviews in Mutation Research

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Cervical cancer is primarily caused by Human papillomavirus (HPV) infection, but other factors such as smoking habits, co-infections and genetic background, can also contribute to its development. Although this cancer is avoidable, it is the fourth most frequent type of cancer in females worldwide and can only be treated with chemotherapy and radical surgery. There is a need for biomarkers that will enable early diagnosis and targeted therapy for this type of cancer. Therefore, a systems biology pipeline was applied in order to identify potential biomarkers for cervical cancer, which show significant reports in three molecular aspects: DNA sequence variants, DNA methylation pattern and alterations in mRNA/protein expression levels. CDH1, CDKN2A, RB1 and TP53 genes were selected as putative biomarkers, being involved in metastasis, cell cycle regulation and tumour suppression. Other ten genes (CDH13, FHIT, PTEN, MLH1, TP73, CDKN1A, CACNA2D2, TERT, WIF1, APC) seemed to play a role in cervical cancer, but the lack of studies prevented their inclusion as possible biomarkers. Our results highlight the importance of these genes. However, further studies should be performed to elucidate the impact of DNA sequence variants and/or epigenetic deregulation and altered expression of these genes in cervical carcinogenesis and their potential as biomarkers for cervical cancer diagnosis and prognosis.

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Section: Cell Cycle Regulation and Dna Repairsupporting

confidence: 86%

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Cardoso

Castelletti

Lima-Filho

et al. 2017

Mutation Research/Reviews in Mutation Research

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“…It has been shown that cell cycle proteins p16, Ki‐67, cyclin D1, p53 and ProEx C are altered in 144 cervical tissue samples, showing increased proliferation . Molecules related to cell proliferation have a significant increase from low‐grade to high‐grade lesions and cancer in HPV‐associated cancers .…”

Section: The Consequences Of Signaling Alterations In Human Papillomamentioning

confidence: 99%

Signaling pathways in HPV‐associated cancers and therapeutic implications

Chen

2015

Reviews in Medical Virology

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Human papillomaviruses (HPVs) are small double-stranded circular DNA viruses with 8 kb genomes. So far, more than 150 HPVs have been identified, and 12 types of HPVs have been conclusively linked to cancer by the International Agency for Research on Cancer/World Health Organization. Expression of HPV E5, E6 and E7 oncoproteins can alter multiple signaling pathways to cause cancer. In this review, the signaling pathways activated by these oncoproteins are summarized, and targeted therapy against key signaling molecules is described. E6 can inactivate tumor protein 53 and PDZ (post synaptic density protein-drosophila disk large tumor suppressor-zonula occludens-1 proteins) while stimulating phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), Wnt and Notch pathways. E7 can inhibit retinoblastoma protein and stimulate the PI3K/Akt pathway. Both E6 and E7 can deregulate cellular microRNA expression, which can alter cellular signaling pathways. E5 can sensitize epidermal growth factor receptor to epidermal growth factor to increase activation of PI3K/Akt and mitogen-activated protein kinase pathways. E5 can also inhibit the extrinsic apoptotic pathway. These altered signaling pathways could be critical for the initiation and maintenance of HPVassociated cancers. Therefore, targeted therapy against the key signaling molecules has therapeutic implications. Among these, the possibilities of targeting PI3K/Akt, mammalian target of rapamycin, epidermal growth factor receptor and vascular endothelial growth factor have been extensively studied in many cancers. Some inhibitors have been studied in cervical cancer in both animal models and clinical trials. Although the results are promising, further investigation is warranted.

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“…In a nested study by Carozzi and colleagues, it was shown that p16 overexpression is a marker for CIN2 or worse or for its development within 3 years in HPV-positive women 123. Ki-67 and p16 are complimentary alternative biomarkers for HPV-related neoplasia 124,125. Cytokeratin (CK) 17 is a useful marker for endocervical reserve stem cells, which gives rise to metaplasia and antibody to CK17 is used to differentiate between immature squamous metaplasia and high-grade CIN (CIN III) 126.…”

Section: Biomarkers Used In Hiv-associated Cervical Cancer Diagnosis/mentioning

confidence: 99%

Biomarkers of HIV-associated Cancer

et al. 2014

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Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin’s lymphoma, and invasive cervical cancer.

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Immunohistochemical Expression of Cyclin D1, p16Ink4a, p21WAF1, and Ki-67 Correlates With the Severity of Cervical Neoplasia

Cited by 28 publications

References 33 publications

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Signaling pathways in HPV‐associated cancers and therapeutic implications

Biomarkers of HIV-associated Cancer

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