Expression of p16 in non-small cell lung cancer and its prognostic significance: A meta-analysis of published literatures

Tong, Jiayi; Sun, Xinchen; Cheng, Hongyan; Zhao, Di; Ma, Jingfei; Zhen, Qing; Cao, Yukun; Zhu, Huiping; Bai, Jianling

doi:10.1016/j.lungcan.2011.04.019

Cited by 38 publications

(20 citation statements)

References 51 publications

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“…The positivity for p16 INK4a has been proposed as a prognostic marker for a more favorable outcome in head and neck squamous cell carcinoma and in lung cancer [31], [32]. Some authors have suggested that p16 INK4a plays a major role not only in suppression of cell division but also in suppression of lymphangiogenesis and lymphatic metastasis [30].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Overexpressed p16INK4a in Patients with Cervical Cancer: A Meta-Analysis

et al. 2014

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Backgroundp16INK4a is a tumor suppressor protein which is induced in cells upon the interaction of high-risk HPV E7 with the retinoblastoma protein by a positive feedback loop, but cannot exert its suppressing effect. Previous reports suggested that p16INK4a immunostaining allows precise identification of even small CIN or cervical cancer lesions in biopsies. The prognostic value of overexpressed p16INK4a in cervical cancer has been evaluated for several years while the results remain controversial. We performed a systematic review and meta-analysis of studies assessing the clinical and prognostic significance of overexpression of p16INK4a in cervical cancer.MethodsIdentification and review of publications assessing clinical or prognostic significance of p16INK4a overexpression in cervical cancer until March 1, 2014. A meta-analysis was performed to clarify the association between p16INK4a overexpression and clinical outcomes.ResultsA total of 15 publications met the criteria and comprised 1633 cases. Analysis of these data showed that p16INK4a overexpression was not significantly associated with tumor TNM staging (I+II vs. III+IV) (OR = 0.75, 95% confidence interval [CI]: 0.35–1.63, P = 0.47), the tumor grade (G1+ G2 vs. G3) (OR = 0.78, 95% CI: 0.39–1.57, P = 0.49), the tumor size (<4 vs. ≥4 cm) (OR = 1.10, 95% CI: 0.45–2.69, P = 0.83), or vascular invasion (OR = 1.20, 95% CI: 0.69–2.08, P = 0.52). However, in the identified studies, overexpression of p16INK4a was highly correlated with no lymph node metastasis (OR = 0.51, 95% CI: 0.28–0.95, P = 0.04), increased overall survival (relative risk [RR]: 0.42, 95% CI: 0.24–0.72, P = 0.002) and increased disease free survival (RR: 0.60, 95% CI: 0.44–0.82, P = 0.001).ConclusionsThis meta-analysis shows overexpression of p16INK4a in cervical cancer is connected with increased overall and disease free survival and thus marks a better prognosis.

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Section: Discussionmentioning

confidence: 99%

Prognostic Significance of Overexpressed p16INK4a in Patients with Cervical Cancer: A Meta-Analysis

et al. 2014

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“…We will cite only those that have been studied with meta-analyses or pooled analyses of selected trials, although published data generally do not allow the study of the independent value of the possible prognostic marker. The following features have been suggested to be associated with a more favourable prognosis: p53 normal status [18]; no EGFR expression [19]; low microvessel count [20]; low VEGF expression [21]; no overexpression of c-erbB-2 [22] with an effect possibly restricted to non-squamous histology [23]; Bcl-2 expression [24]; low KI67 expression [25]; absence of KRAS mutation [26]; TTF-1 positivity [27]; high level of p16 expression [28]; low or no ERCC1 expression (advanced NSCLC treated with platinum-based chemotherapy) [29]; low class III b-tubulin expression, in resected patients [30]; low survivin expression, in resected patients only [31]; and low lymphatic microvessel density, in surgically treated patients [32]. Regarding the prognostic value of angiogenesis, microvessel count was confirmed as prognostic factor in a meta-analysis based on individual data, only if assessed by the Chalkley method [33].…”

Section: Other Biomarkersmentioning

confidence: 99%

Prognostic and predictive factors for lung cancer

Paesmans

2012

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“…For example, in sinonasal undifferentiated carcinomas, most of the tumors overexpress p16 but none have been found to harbor HPV [17]. Similarly, in several types of lung non-small cell carcinoma, p16 is overexpressed in as many as 60% of cases, unassociated with the presence of HPV [18]. However, different cancer types and organ systems are biologically unique, so extrapolation to other tumors and subsites is not necessarily helpful or useful.…”

Section: Introductionmentioning

confidence: 99%

p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

Lewis

2012

Head and Neck Pathol

210

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It is widely acknowledged that human papillomavirus (HPV)-related oropharyngeal carcinoma is a biologically unique form of head and neck cancer that should be singled out and treated differently. It is now incumbent to find a test (or combination of tests) that accurately identifies cancers with the associated favorable prognosis for proper patient counseling and management and for placing patients in the correct treatment arms in the emerging clinical trials that are attempting to establish unique treatment types and approaches. The test (or combination of tests) that are utilized must be widely available, reliable, easy to interpret, and wellvalidated. While HPV-specific testing seems completely logical to use as a single test or one of a combination of tests, it turns out to be quite complicated in practice. Because of the different forms of the virus, the differing types of HPV-specific tests can give different information. HPV DNA, RNA, and protein assays have varying sensitivities for virus detection and also varying availability from formalin-fixed, paraffin-embedded tissue. Since p16 protein over expression is very sensitive for the presence of transcriptionally-active HPV and since it correlates strongly with patient outcomes, is widely available, and easy to interpret, it appears to currently be the single test that combines all of the desired attributes in a risk stratification marker for widespread implementation in clinical and research study settings. This article will review the literature on p16 immunohistochemistry and its relation to HPV-specific testing, discuss some practical issues related to its implementation, and present the case for why it should be the single test used for this purpose.

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Expression of p16 in non-small cell lung cancer and its prognostic significance: A meta-analysis of published literatures

Cited by 38 publications

References 51 publications

Prognostic Significance of Overexpressed p16INK4a in Patients with Cervical Cancer: A Meta-Analysis

Prognostic Significance of Overexpressed p16INK4a in Patients with Cervical Cancer: A Meta-Analysis

Prognostic and predictive factors for lung cancer

p16 Immunohistochemistry As a Standalone Test for Risk Stratification in Oropharyngeal Squamous Cell Carcinoma

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