Expression of p21WAF1/CIP1 in adenocarcinoma of the uterine cervix

Lu, Xuanyong; Toki, Toshihiko; Konishi, Ikuo; Nikaido, Toshio; Fujii, Shingo

doi:10.1002/(sici)1097-0142(19980615)82:12<2409::aid-cncr15>3.0.co;2-t

Cited by 65 publications

(16 citation statements)

References 35 publications

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“…In a study without HPV analysis, Lu et al [18] found enhanced expression of these cell-cycle inhibitors in most cervical adenocarcinomas relative to normal endocervical glands. However, to enhance our understanding of the role of these proteins in cervical cancer, the papillomavirus infections which influence their expression or function should be considered.…”

Section: Introductionsupporting

confidence: 40%

“…Detectable p16 expression has been described in 58% of cervical adenocarcinomas in a prior study [18]. The higher percentage of p16-positive tumors found by us is probably due to the highly sensitive immunohistochemistry protocol used in this study.…”

Section: Discussionmentioning

confidence: 99%

“…It is now widely accepted that nearly 100% of cervical squamous cell carcinomas (SCC) are associated with certain highrisk human papillomavirus types, mainly HPV 16,18,31,33,35,45 [34]. Malignant transformation of the cervical epithelial cells is associated with expression of the viral oncogenes E6 and E7 with dramatic implications for cell cycle regulation, differentiation, and genomic stability [32,40].…”

Section: Introductionmentioning

confidence: 99%

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Expression of cyclin-dependent kinase inhibitors p16MTS1, p21WAF1, and p27KIP1 in HPV-positive and HPV-negative cervical adenocarcinomas

et al. 2001

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Inactivation or down-regulation of the cell-cycle inhibitors p16MTS1, p21WAF1, and p27KIP1 is involved in the carcinogenesis of various human tumors. In cervical squamous cell carcinomas that are associated with human papillomavirus (HPV) infection, the expression or function of these proteins is impaired by the action of viral oncoproteins E6 and E7. Comparably less is known about the role of these cyclin-dependent kinase inhibitors in cervical adenocarcinomas, 15-40% of which are HPV negative. Therefore, we studied the expression of p16MTS1, p21WAF1, and p27KIP1 by immunohistochemistry in 60 cervical adenocarcinomas. HPV infection was determined by PCR, and HPV 16 and 18 E6/E7 oncogene expression was analyzed by RNA-RNA in situ hybridization. We found significant correlations of strong p16 expression with HPV 16/18 infection and HPV 16/18 E6/E7 oncogene expression (P=0.001). Moderate or strong p16 expression was also observed in 41% of HPV-negative carcinomas, indicating that HPV-independent mechanisms might also lead to p16 overexpression. In addition, stronger p21 and p27 expression was significantly associated with the detection of HPV 16 or 18 E6/E7 transcripts (P=0.015 and 0.030, respectively). Obviously, the tumor suppressor action of these proteins can be overcome in HPV-positive lesions. In contrast, absent or low p16, p21, and p27 immunostaining was observed in most HPV-negative cervical adenocarcinomas and might contribute to carcinogenesis in these tumors.

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Section: Introductionsupporting

confidence: 40%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of cyclin-dependent kinase inhibitors p16MTS1, p21WAF1, and p27KIP1 in HPV-positive and HPV-negative cervical adenocarcinomas

et al. 2001

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“…adenocarcinoma of the cervix had a statistically significant correlation with poor outcome. Conversely, Lu et al (4) reported that p53 expression was not correlated with the prognosis of cervical adenocarcinoma. In our study, p53 overexpression has no significant association with outcome of cervical SCC treated with cCRT.…”

Section: Discussionmentioning

confidence: 99%

“…A study by Kihara et al (3) showed that overexpression of the c-erbB2 proto-oncogene product was greater in patients with advanced clinical stage disease and indicated a poor prognosis. Lu et al (4) reported that expression of the p21/waf1/cip1 product correlated with a favorable prognosis. The cellcycle-associated proteins p53, p21/waf1/cip1, molecular immunology borstel-1 (MIB-1), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2) and Bcl-2, commonly reported as prognostic factors in many other sites, were the subjects of this immunohistochemical study.…”

Section: Introductionmentioning

confidence: 99%