Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma: Correlation with clinical outcome

Graflund, Marianne; Sorbe, Bengt; Karlsson, Mats G.

doi:10.1046/j.1525-1438.2002.01113.x

Cited by 14 publications

(18 citation statements)

References 29 publications

(39 reference statements)

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“…p53-positive immunostaining is unexpected and may be caused by TP53 gene mutation or abnormal accumulation of an inefficient p53 protein in the absence of gene mutation (22). We have observed high p53 positivity in all groups, which corroborates its possible role in cervical carcinogenesis; however, p53 did not prove to be a good biomarker for distinguishing low-from high-grade lesions, as previously reported (24,25). However, this has not been the findings in many studies (7,9,23).…”

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confidence: 49%

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

Portari

Russomano

Camargo

et al. 2013

International Journal of Gynecological Pathology

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High-risk human papillomaviruses are closely associated with cervical cancer and its precursor lesions through interactions between the E6 and E7 oncoproteins and the cell-cycle regulatory proteins, such as p53 and pRb, respectively. As other molecules involved in the cell-cycle control seem to be important for human papillomavirus (HPV)-mediated cervical carcinogenesis, we have analyzed the expression of p53, p21, p16, cyclin D1, and Ki-67 and the presence of HPV (HPV pool and HPV-16) by immunohistochemical studies using tissue microarray in low squamous intraepithelial lesions (n=50), high squamous intraepithelial lesions (n=98), and cervical carcinoma (n=18). We have found a significant increase in the expression of p16 and p21 (P<0.001) from low- to high-grade lesions and cancer. In contrast, cyclin D1 expression showed a significant decrease in more severe lesions (P<0.001). p16, Ki-67, p21, and p53 positivity increased with the cell-layer level and the lesion severity, with stronger correlations being observed for p16 and Ki-67. High positivity for HPV pool (96.3%) and HPV-16 (77.5%) immunostaining was detected in all cases, with an association between p16 and cyclin D1 expression and HPV-16 infection. Our tissue microarray results corroborate the usefulness of the immunohistochemical assessment of cell-cycle biomarkers in distinguishing different groups of precursor lesions of the cervix and cervical carcinoma.

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confidence: 49%

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

Portari

Russomano

Camargo

et al. 2013

International Journal of Gynecological Pathology

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“…Cervix Cancer. Several reports, 18,[72][73][74][75][76][77][78][79] have addressed the significance of bcl-2 overexpression to treatment outcome for cervix cancer with similar disparity (Table 5) as reported for apoptotic index in Table 1.…”

Section: Assessment Of Apoptotic Cells ("Apoptotic Index")mentioning

confidence: 89%

Apoptosis Genes and Resistance to Cancer Therapy: What Does the Experimental and Clinical Data Tell Us?

Brown

Wilson²

2003

Cancer Biology & Therapy

109

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The dominant paradigm in cancer treatment is that cancer cells die from the common pathway of apoptosis subsequent to DNA damage by anticancer agents and that cells resistant to apoptosis are resistant to therapy. In this review we trace the logic that brought about this view and discuss whether the clinical and experimental data that have now accumulated over the past decade support the position. We show that there is support for the apoptosis model only for certain malignancies of hematopoietic origin. For the majority of cancers (which are of epithelial origin), even though some may exhibit apoptosis after treatment, there is little or no support for the concept that apoptosis, and the genes that govern it, determine the response to therapy. In general, whether apoptosis matters for overall tumor response depends on how soon after treatment apoptosis occurs. If it occurs early (within 4 to 6 hours after treatment), it is likely to be important for determining the overall response of the cell or tumor. This is the case for some tumors of myeloid and lymphoid origin. On the other hand, if apoptosis occurs long after exposure, 24-48 hrs, and usually after mitosis, then it is unlikely to be the determinant of cytotoxicity, and modifying it is unlikely to affect overall cell killing. This is the situation for most, if not all, tumors of epithelial or mesenchymal origin. What then causes cancer cells to die following treatment with anticancer agents? The evidence from ionizing radiation is clear: DNA damage leading to chromosome breaks. We argue that the situation is similar for most anticancer drugs. Indeed inability to repair the DNA damage produced by these agents, and the levels of the proteins involved in these repair processes, may explain the treatment sensitivity of some cancers. Further clinical studies in this area are needed.

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“…Studies of p21 expression in cervical cancer have reported higher levels of expression of p21 in cancer tissue compared to normal tissue [28,29], while others showed there is no association between the expression of p21 and the pathological features of cervical cancer [30]. After infection with HPV, the E6 protein of HPV promotes p53 degradation and thus inhibits p21 expression and function.…”

Section: Discussionmentioning

confidence: 99%

Association of p21 SNPs and risk of cervical cancer among Chinese women

Wang

Zhang

et al. 2012

BMC Cancer

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BackgroundThe p21 codon 31 single nucleotide polymorphism (SNP), rs1801270, has been linked to cervical cancer but with controversial results. The aims of this study were to investigate the role of p21 SNP-rs1801270 and other untested p21 SNPs in the risk of cervical cancer in a Chinese population.MethodsWe genotyped five p21 SNPs (rs762623, rs2395655, rs1801270, rs3176352, and rs1059234) using peripheral blood DNA from 393 cervical cancer patients and 434 controls.ResultsThe frequency of the rs1801270 A allele in patients (0.421) was significantly lower than that in controls (0.494, p = 0.003). The frequency of the rs3176352 C allele in cases (0.319) was significantly lower than that in controls (0.417, p < 0.001).The allele frequency of other three p21 SNPs showed not statistically significantly different between patients and controls. The rs1801270 AA genotype was associated with a decreased risk for the development of cervical cancer (OR = 0.583, 95%CI: 0.399 - 0.853, P = 0.005). We observed that the three p21 SNPs (rs1801270, rs3176352, and rs1059234) was in linkage disequilibrium (LD) and thus haplotype analysis was performed. The AGT haplotype (which includes the rs1801270A allele) was the most frequent haplotype among all subjects, and both homozygosity and heterozygosity for the AGT haplotype provided a protective effect from development of cervical cancer.ConclusionsWe show an association between the p21 SNP rs1801270A allele and a decreased risk for cervical cancer in a population of Chinese women. The AGT haplotype formed by three p21 SNPs in LD (rs1801270, rs3176352 and rs1059234) also provided a protective effect in development of cervical cancer in this population.

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Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma: Correlation with clinical outcome

Cited by 14 publications

References 29 publications

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

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

Apoptosis Genes and Resistance to Cancer Therapy: What Does the Experimental and Clinical Data Tell Us?

Association of p21 SNPs and risk of cervical cancer among Chinese women

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