The expression of metaloproteinases-2 and -9 is different according to the patterns of growth and invasion in squamous cell carcinoma of the penis

Soares, Fernando Augusto; Cunha, Isabela Werneck da; Guimarães, Gustavo Cardoso; Nonogaki, Sueli; Campos, Rodrigo Sousa Madeira; Lopes, Ademar

doi:10.1007/s00428-006-0299-x

Cited by 7 publications

(6 citation statements)

References 42 publications

(41 reference statements)

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“…As activation of TGF-β/Smad2/3 pathway has already been demonstrated to be involved in the malignant progression and dissemination of various cancer types, it would be reasonable to propose that the effects of CEACAM19 might partly result from its function in regulating the Smad2/3 activation, thus promoting the metastasis of penile cancer 34. Soares et al showed that penile cancers with over-expression of two metastasis-related molecules MMP2 and MMP9 were deeply invasive 35. Similarly, we observed that the secretion of MMP2 and MMP9 was markedly down-regulated in Penl1 cells with CEACAM19 knockdown or treated with TGF-β/Smad2/3 inhibitor SB431542, suggesting CEACAM19 might regulate the metastatic phenotype of penile cancer via modulating Smad2/3 and its downstream MMP2/9 expression.…”

Section: Discussionmentioning

confidence: 99%

Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer

Hu¹,

Chen²,

Li³

et al. 2019

CMAR

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ObjectiveA greater knowledge of the mechanisms of the pathogenesis of penile cancers may assist in the development of more tailored targeted therapy. Herein, we aimed to evaluate the expression of CEACAM19 in penile cancer and to explore its regulatory mechanisms.Material and methodsThis retrospective study enrolled 64 penile cancer patients who underwent penectomy between 2011 and 2015. CEACAM19 expression in tissues was detected by immunohistochemistry, which was analyzed in association with clinicopathological parameters. Kaplan–Meier analysis was performed to evaluate the relationship between CEACAM19 expression and prognosis of patients with penile cancer. Cell Counting Kit-8 assay and clonogenic assay were used to evaluate the cell viability and tumorigenic potential of penile cancer cell line, respectively; wound healing assay and transwell invasion assay were conducted to evaluate the effect of CEACAM19 depletion on cell migration and invasion in penile cancer cells; CEACAM19 protein expression was analyzed by Western blotting. Culture supranatant matrix metalloproteinase 2/9 (MMP2/9) was detected by ELISA.ResultsCEACAM19 was differentially expressed in non-cancerous and penile cancer tissues. Over-expression of CEACAM19 was significantly associated with nodal and distant metastasis, and predicted unfavorable cancer-specific survival in penile cancer. Depletion of CEACAM19 expression suppressed cell proliferation, reduced colony formation, and attenuated cell migration and invasion in Penl1 cells. Furthermore, knockdown of CEACAM19 expression attenuated the levels of p-Smad2/3 and reduced secretion of MMP2/9 in Penl1 cells. The effects of CEACAM19 might result from its function in regulating the Smad2/3 activation, as inhibition on Smad2/3 activation suppressed cell migration and invasion and reduced MMP2/9 secretion in Penl1 cells.ConclusionOver-expression of CEACAM19 might serve as a potential prognostic biomarker for clinical management of penile cancer. Strategies targeting CEACAM19-regulated signaling pathways may have a therapeutic benefit in penile cancer.

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Section: Discussionmentioning

confidence: 99%

Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer

Hu¹,

Chen²,

Li³

et al. 2019

CMAR

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“…Lymph node metastases (RR = 57.9; 95% CI = 7.4 -453.9), urethral infiltration (RR = 3.5; 95% CI = 1.3 -9.2) and MMP-9 immunoreactivity (RR = 3.2; 95% CI = 1.2 -8.3) were considered independent risk factors for disease recurrence. Soares et al [112] examined whether the expression of MMP-2 and MMP-9 is different according to the patterns of tumor growth and invasion in 115 patients with SCC of the penis. The findings of this series allowed it to be concluded that less differentiated tumors, which are more invasive and with a pattern of invasion in small group of cells, are associated with the overexpression of MMPs.…”

Section: Tumor Markers and Prognosismentioning

confidence: 99%

“…Papers analyzing even the most common molecules involved with carcinogenesis, tumor progression and metastases are scarce in the literature. Almost nothing is known about penile SCC genetics and molecular markers, especially when compared with knowledge about SCC from other sites, such as cervical and head/neck tumors [112] . The author's department, from 1953 to 2000, has recorded 799 patients with penile carcinoma.…”

Section: Expert Opinionmentioning

confidence: 99%

Prognostic factors and biomarkers of penile carcinoma

Lopes

2008

Expert Opinion on Medical Diagnostics

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Penile squamous cell carcinoma (SCC) is a rare malignancy with highest incidence in underdeveloped and developing countries. Oncogenic human papilloma virus (HPV) DNA, mainly types 16 and 18, are found in ∼ 100% of patients with uterine cervix carcinoma. The incidence of this virus in SCC and its variations range from 30.5 to 80%. Despite controversies, contrary to the cervical carcinoma, in the carcinogenesis and disease progression of SCC, HPV-dependent and HPV-independent tumors need to be considered. Lymphadenectomies continue to be the gold standard treatment of lymph node metastases. Undesirable accuracy on staging system methods and high rates of lymphadenectomy complications are the principal objections to these surgical procedures; therefore, the main issue in patients with SCC is to know who should or should not undergo lymphadenectomy. The search for primary tumor anatomopathological and biomarker risk factors for lymph node metastases, such as has occurred in other tumors, may be an important tool to select lymphadenectomies candidates better. Histological subtypes, tumor grade, growth pattern, tumor thickness, lymphatic embolization by neoplasic cells and depth of infiltration have been reported as important prognostic factors for lymph node metastases. In our series, lymphatic vascular permeation, palpable lymph node after primary tumor control (cN stage), pattern of invasion, p53 and PCNA immunoreactivity are independent lymph node metastases risk factors in the multivariate model. It is strongly recommended that patients be concentrated in specialized centers or cancer hospitals and multi-centric prospective studies carried out on tumor markers in this rare disease, in order to stage better lymph node disease and avoid unnecessary surgeries with high morbidity rates.

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“…Foi analisado o percentual de células neoplásicas coradas, considerando apenas expressão citoplasmática nas células tumorais. Os casos foram graduados conforme o seguinte critério: 0 -negativa: < 5% de células; 1 -positividade fraca: 5% a 20% das células; 2 -positividade moderada: 21% a 50% das células; 3 -positividade forte: > 50% (32) .…”

Section: Análise Imuno-histoquímicaunclassified

“…Assim, a invasão de um tumor epitelial é uma etapa essencial para a progressão do câncer, incluindo os tumores de esôfago (6) . Nesse sentido, a degradação dos componentes da matriz extracelular confere ao tumor de esôfago a possibilidade de invasão local para tecidos adjacentes, além de permitir o acesso aos vasos sanguíneos e linfáti-cos, proporcionando a disseminação a distância (5,32,36) . A degradação dos componentes da matriz extracelular é mediada por uma família de enzimas proteolíticas, denominadas metaloproteinases de matriz (MMPs).…”

Section: Introductionunclassified

Expressão imuno-histoquímica das metaloproteinases 2 e 9 não está associada à progressão do carcinoma de células escamosas de esôfago

Felin¹,

Grivicich²,

Felin³

et al. 2009

J. Bras. Patol. Med. Lab.

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Introdução: O carcinoma de células escamosas do esôfago está entre os tipos mais agressivos de câncer e de pior prognóstico. As metaloproteinases de matriz (MMPs), especialmente as MMP-2 e MMP-9, vêm sendo utilizadas para avaliação prognóstica do câncer, associadas a invasão, tamanho e crescimento tumoral. Objetivo: O presente estudo visa investigar as expressões imuno-histoquímicas de MMP-2 e MMP-9, avaliando se existe correlação entre sua expressão e o estadiamento tumoral, invasão vascular, invasão local (pT) e diferenciação tumoral no carcinoma de células escamosas de esôfago. Material e Método: Foi realizado um estudo retrospectivo utilizando 31 blocos de parafina contendo tumores de carcinoma escamoso esofágico, obtidas por esofagectomias realizadas entre 1998 e 2003, no Hospital Universitário de Santa Maria (HUSM). Os cortes histológicos foram submetidos à reação imuno-histoquímica, com sistema de amplificação por polímero não-biotinilado Novolink para detecção de MMP-2 e MMP-9. Resultados: A avaliação da MMP-2 apresentou positividade fraca em apenas cinco casos, não demonstrando correlação com as variáveis estudadas. Também não foram observadas associações significativas entre as variáveis do estudo e o grau de expressão imuno-histoquímica da MMP-9. Conclusão: A expressão imuno-histoquímica das MMP-2 e MMP-9 não parece ser influenciada pelos parâmetros investigados. Nesse sentido, estudos adicionais são necessários para melhor compreensão de sua associação aos fatores prognósticos do carcinoma de células escamosas de esôfago.

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The expression of metaloproteinases-2 and -9 is different according to the patterns of growth and invasion in squamous cell carcinoma of the penis

Cited by 7 publications

References 42 publications

Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer

Aberrant CEACAM19 expression is associated with metastatic phenotype in penile cancer

Prognostic factors and biomarkers of penile carcinoma

Expressão imuno-histoquímica das metaloproteinases 2 e 9 não está associada à progressão do carcinoma de células escamosas de esôfago

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