E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: Analysis of 125 patients

Campos, Rodrigo Sousa Madeira; Lopes, Ademar; Guimarães, Gustavo Cardoso; Carvalho, André Lopes; Soares, Fernando Augusto

doi:10.1016/j.urology.2005.10.026

Cited by 69 publications

(10 citation statements)

References 20 publications

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“…It is therefore implicated in cancer metastases, particularly in squamous cell carcinoma [ 35 , 36 ]. Campos and colleagues [ 8 ], using the conventional, subjective expression ‘scoring’ technique, have suggested that two members of the MMP family (MMP2 and MMP9) are over-expressed in penile carcinoma. Similar to MMP7 [ 17 ], both MMP2 and MMP9 are likely targets of Wnt-ß-catenin transcription activation [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Mentrikoski et al [ 5 ], using conventional semi-quantitative scoring methods [ 6 ], have suggested that p53, CD1 and EGFR over-expression may contribute towards carcinogenesis; CD1 expression has also been co-related with tumor differentiation [ 7 ]. In a large sample cohort (125 patients) E-cadherin and MMPs 9 and 2, were found to be putative prognostic markers of PeCa [ 8 ]. Mutation in c-rasHa gene [ 9 ] and activity of cyclo-oxygenase 2 (COX2) [ 10 ] have been associated with metastatic PeCa.…”

Section: Introductionmentioning

confidence: 99%

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Targets of Wnt/ß-Catenin Transcription in Penile Carcinoma

et al. 2015

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Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p<0.01). Expression of all proteins, except CD1, showed a significant decrease in grade II compared to grade I tumors. High magnification, deconvolved confocal images were used to measure differences in co-localization between the four proteins. Significant (p<0.04-0.0001) differences were observed for various permutations of the combinations of proteins and state of the tissue (control, tumor grades I and II). Wnt signaling may play an important role in PeCa and proteins of the Wnt signaling network could be useful targets for diagnosis and prognostic stratification of disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targets of Wnt/ß-Catenin Transcription in Penile Carcinoma

et al. 2015

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“…Yang et al identified STAT3 as one of the top oncogenic pathways upregulated in PC 41 . Campos et al indicated that high MMP-9 expression was an independent risk factor for disease recurrence in PC 42 . Our present findings reveal that knockdown of CCL20 attenuated AKT and STAT3 signaling and reduced MMP2/9 secretion, suggesting the effect of CCL20 might result from its function in activating oncogenic signaling pathways (STAT3, AKT) and enhancing the expression of metastasis-related MMP2/9, thus promoting the tumor progression of PC.…”

Section: Discussionmentioning

confidence: 99%

High serum CCL20 is associated with tumor progression in penile cancer

Tong

Huang

et al. 2020

J. Cancer

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Serum cancer biomarker has been proven to be very valuable in cancer diagnosis, disease monitoring and prognosis assessment, despite there is still a lack of serum biomarker for penile cancer (PC). Our initial analysis on public GEO dataset identified CCL20 as a top C-C motif ligand (CCL) gene enriched in PC. The patients with PC exhibited markedly higher preoperative serum CCL20 level than healthy control. The area under the curve (AUC) was 0.855 with the sensitivity of 72.4%, and specificity of 93.5% to distinguish PC. Preoperative serum CCL20 level was significantly associated with clinicopathological characteristics including T stage ( P =0.005), nodal status ( P =0.008), and pelvic lymph node metastasis ( P =0.007). PC Patients with high serum CCL20 level had shorter disease-free survival compared to those with low level ( P <0.001). Cox regression analysis showed that serum CCL20 level could serve as an independent prognostic factor for disease-free survival with a HR of 3.980 (95% CI: 1.209-13.098, P =0.023). Furthermore, CCL20 expression was observed in PC tissues and cell lines. Knockdown of CCL20 expression markedly suppressed malignant phenotypes (cell proliferation, clonogenesis, apoptosis escape, migration and invasion), attenuated STAT3 and AKT signaling and reduced MMP2/9 secretion in PC cell lines. Consistently, CCL20 and its receptor CCR6 exhibited correlated expression pattern in PC tissues. In conclusion, serum CCL20 level might serve as a potential diagnostic and prognostic cancer biomarker for PC. CCL20 might activate multiple downstream oncogenic signaling pathways (STAT3, AKT, MMP2/9) to promote malignant progression of PC, which may warrant further investigation in the future.

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“…Markers that can be readily evaluated by IHC would be of great value to better select patients to inguinal node resection and adjuvant treatment. Although other markers have already been proposed [38,39], none is currently used in the clinical practice. We also observed that patients who presented AR cytoplasmic staining showed a lower overall survival (P = 0.032).…”

Section: Discussionmentioning

confidence: 99%

Nuclear loss and cytoplasmic expression of androgen receptor in penile carcinomas: role as a driver event and as a prognosis factor

et al. 2018

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Androgen receptor (AR) is a member of the steroid and nuclear family receptor that acts as transcription factor. AR signaling plays pivotal role in the development and progression of prostate cancer. However, the role of AR in penile cancer (PeCa) is poorly explored. Our previous molecular studies unveiled frequent AR mRNA loss in PeCa, which was further predicted as a major driver alteration in this neoplasm. Herein, we assessed the AR protein expression in 59 usual PeCa tissues and 42 surrounding normal tissues (SNT) by immunohistochemistry using a tissue microarray. In a paired analysis, we found a total absence of nuclear AR expression in PeCa while 95.2% of SNT samples presented strong nuclear AR expression (P < 0.001). Interestingly, 17 of 42 PeCa presented weak or moderate cytoplasmic AR staining, contrasting with 5 of 42 SNT (P = 0.008). Increased levels of AR cytoplasmic expression were related with poor prognosis features including advanced clinical staging (P = 0.044), compromised surgical margins (P = 0.005), and pathological inguinal node status (P = 0.047). Furthermore, AR cytoplasmic expression was also related with shorter overall survival (P = 0.032). In conclusion, the frequent loss of nuclear AR protein levels suggests a potential function in PeCa development. Based on this result, the androgen deprivation therapy is not indicated for PeCa patients. In addition, the AR cytoplasmic expression found in a significant number of cases (40.5%) showed prognostic value and pathways activated by the non-genomic AR signaling may represent a promising therapeutic strategy.

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E-cadherin, MMP-2, and MMP-9 as prognostic markers in penile cancer: Analysis of 125 patients

Cited by 69 publications

References 20 publications

Targets of Wnt/ß-Catenin Transcription in Penile Carcinoma

Targets of Wnt/ß-Catenin Transcription in Penile Carcinoma

High serum CCL20 is associated with tumor progression in penile cancer

Nuclear loss and cytoplasmic expression of androgen receptor in penile carcinomas: role as a driver event and as a prognosis factor

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