The role of perineural invasion in penile cancer: a meta-analysis and systematic review

Zhou, Xiang; Qi, Feng; Zhou, Ruhua; Wang, Shangqian; Wang, Yamin; Wang, Yichuan; Chen, Chen; Wang, Yichun; Yang, Jie; Song, Ninghong

doi:10.1042/bsr20180333

Cited by 19 publications

(13 citation statements)

References 37 publications

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“…They also added higher neutrophil-to-lymphocyte ratios (NLR) and squamous cell carcinoma antigen (SCC-Ag) overexpression to the above list of biochemical predictors (23). Zhou et al performed a meta-analysis of exclusively perineural invasion and its ability to predict inguinal lymph node metastasis; they showed a statistically significant higher rate of LNM in penile SCC with perineural invasion compared to that in which nerve invasion is absent (25).…”

Section: Pertinent Meta-analysesmentioning

confidence: 99%

Prognostic predictors of lymph node metastasis in penile cancer: a systematic review

et al. 2021

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Purpose: Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with signifi cant morbidity and mortality. A crucial prognostic factor is the presence of inguinal lymph node metastases (ILNM) at the time of diagnosis. At least 25% of cases have micrometastases at the time of diagnosis. Therefore, we performed a literature review of studies evaluating factors, both clinical and pathological, predictive of lymph node metastases in penile SCC. Materials and methods: Studies were identifi ed using PubMed and search terms included the following: penile cancer, penile tumor, penile neoplasm, penile squamous cell carcinoma, inguinal lymph node metastasis, lymph node metastases, nodal metastasis, inguinal node metastasis, inguinal lymph node involvement, predictors, and predictive factor. The number of patients and predictive factors were identifi ed for each study based on OR, HR, or RR in multivariate analyses, as well as their respective signifi cance values. These were compiled to generate a single body of evidence supportive of factors predictive of ILNM in penile SCC. Results: We identifi ed 31 studies, both original articles and meta-analyses, which identifi ed factors predictive of metastases in penile SCC. The following clinical factors were predictive of ILNM in penile SCC: lymphovascular invasion (LVI), increased grade, increased stage (both clinical and pathological), infi ltrative and reticular invasion, increased depth of invasion, perineural invasion, and younger patient age at diagnosis. Biochemically, overexpression of p53, SOD2, Ki-67, and ID1 were associated with spread of SCC to inguinal lymph nodes. Diffuse PD-L1 expression, increased SCC-Ag expression, increased NLR, and CRP >20 were also associated with increased ILNM. Conclusions: A multitude of factors are associated with metastasis of SCC of the penis to inguinal lymph nodes, which is associated with poor clinical outcomes. The above factors, most strongly LVI, grade, and node positivity, may be considered when constructing a nomogram to risk-stratify patients and determine eligibility for prophylactic inguinal lymphadenectomy.

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Section: Pertinent Meta-analysesmentioning

confidence: 99%

Prognostic predictors of lymph node metastasis in penile cancer: a systematic review

et al. 2021

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“…9 Yet differing outcomes between studies warrant validation of the role of LVI as an independent prognostic indicator of reduced survival in patients with penile carcinoma. 9 Studies have demonstrated clinicopathological variables, such as inguinal lymph node metastases, perineural invasion, tumor stage, and grade, to be predictors of poor survival [10][11][12] ; however, there are socioeconomic and psychosocial factors that influence survival risk. Demographic and socioeconomic predictors, such as lower education attainment, African-American, and Hispanic ethnicity, have been shown to be associated with poor survival.…”

Section: Introductionmentioning

confidence: 99%

Novel Prognostic Models for Patients With Penile Carcinoma

et al. 2020

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Although penile carcinoma is a rare malignancy, there is still an unmet need to identify prognostic factors associated with poor survival. In this study, we utilized demographic and clinical information to identify the most informative variables associated with overall survival in patients with penile cancer. From a full model including all covariates found to be statistically significant in univariable analyses, we identified a parsimonious reduced model containing tumor site (penis glans: hazard ratio [HR] = 0.48; 95% CI: 0.28-0.85 and penis not otherwise specified: HR = 0.45; 95% CI: 0.25-0.84), undetermined tumor differentiation (HR = 0.48; 95% CI: 0.27-0.86), and TNM stage III/IV (HR = 2.83; 95% CI: 1.68-4.75). When all of the covariates from the full model were subjected to classification and regression tree analysis, we identified 6 novel risk groups. Of particular interest, we found marriage was associated with substantial improvement in survival among men with the same stage and disease site. Specifically, among single/widowed/divorced men with TNM stage 0-II and prepuce/penis corpus/overlapping lesions had worse survival (5-year survival = 18.2%) versus married men (5-year survival = 62.5%). Since marital status is linked to social support, these findings warrant a deeper investigation into the relationships between disease prognosis and social support in patients with penile carcinoma.

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“…The data presented in this work demonstrate that miR-145 is a potential biomarker of perineural invasion (PNI). In previous studies, PNI has been recognized as a prognostic indicator of poor survival in patients with PC (27). The downregulation of miR-145 is associated with poor PFS (progression-free survival) in patients with lung cancer, colorectal cancer, esophageal cancer, breast cancer, and glioma (28).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-145 is associated with perineural invasion in penile carcinoma

et al. 2021

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Background: Human papillomavirus (HPV) infection is a risk factor for penile cancer (PC). The miR-145 expression has been correlated to this virus genomic amplification. In this context, this work aims to determine the expression level of miR-145 in penile tumors infected by high-risk HPV and correlate it with the clinicopathological characteristics of the tumor and protein expression of p53.Methods: Formalin-fixed paraffin-embedded from 52 patients with PC, at diagnosis and prior to any cancer treatment, were obtained. HPV identification was performed by nested type PCR, and miR-145 expression was obtained by qRT-PCR. Immunohistochemical analysis of p53 and Ki-67 was performed.Results: Tumoral miR-145 expression was significantly lower compared to adjacent tissue. Additionally, there was a significant reduction of miR-145 expression in invasion perineural, histological associated HPV, and absence of p53 expression in positive HPV cases. HPV infection was detected in 86.5%, the most frequent HPV16. Reduced disease-free survival was observed in patients with low expression of miR-145.Conclusions: Our data suggest that the underexpression of miR-145 may be triggered by HPV action, decreasing protein expression of p53, and being correlated with perineural invasion. Therefore, the deregulation of miR-145 provides clues as to the potential role in penile carcinogenesis and is also a potential candidate for validation in noninvasive samples.

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The role of perineural invasion in penile cancer: a meta-analysis and systematic review

Cited by 19 publications

References 37 publications

Prognostic predictors of lymph node metastasis in penile cancer: a systematic review

Prognostic predictors of lymph node metastasis in penile cancer: a systematic review

Novel Prognostic Models for Patients With Penile Carcinoma

Downregulation of miR-145 is associated with perineural invasion in penile carcinoma

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