Apoptosis in Breast Carcinoma

González‐Cámpora, Ricardo; Ruiz, María Rosa Galera; Ramírez, Francisco Vázquez; Ríos-Martín, Juan José; Santos, José María Fernández; Martos, María del Mar Ramos; Pascual, Alfons

doi:10.1016/s0344-0338(00)80097-7

Cited by 26 publications

(24 citation statements)

References 41 publications

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“…Furthermore, in gastric cancer significant relationships between TUNEL, Ki67 and grade have been reported (Jesionek-Kupnicka et al, 2002), whereas in oral leukoplakia higher levels of TUNEL, Ki67 and p53 have been reported, indicating increased instability of the genome and higher severity of the dysplasia and the clinical stage (Kovesi and Szende, 2004). Ki67 and p53 were strongly expressed in high-grade prostate cancer tumours (Szabo et al, 2000), and higher grade breast carcinoma tumours have been reported as characterised by higher levels of p53 and TUNEL staining (Gonzalez-Campora et al, 2000). Bladder cancer grade, p53, Ki67, TUNEL and poor survival have been positively correlated (Shiina et al, 1999) and similar results have been found for both non-Hodgkin's lymphoma.…”

Section: Discussionmentioning

confidence: 99%

TUNEL – an efficient prognosis predictor of salivary malignancies

et al. 2007

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Biological markers are necessary for predicting prognosis of salivary malignancies and better understanding the pathogenesis of salivary cancer. We analysed terminal deoxynucleotidyl transferase (TdT)-mediated biotinylated deoxyuridine-triphosphate (dUTP)-biotin nick-end labelling (TUNEL), p53 and Ki67 expression in 66 patients with malignant salivary tumours by immonohistochemistry, and correlated the data with survival, disease-free survival, tumour grade, stage, and local and distant metastasis. TUNEL efficiently predicted poor prognosis in salivary malignancies. The 5-year (5Y) survival probability dropped significantly with the level of TUNEL staining (from 83% in negatively stained tumours to 57 and 24% in TUNEL positively stained levels 1 and 2, respectively), (P ¼ 0.042). Extensive Ki67 staining (in addition to TUNEL) reduced the 5Y-survival rate even further and addition of positively stained p53 dropped the 5Y-survival rate to 0. The correlation rates between TUNEL and Ki67 was 58% (P ¼ 0.0001), and between TUNEL and p53 it was 50% (P ¼ 0.035). Concurrently, TUNEL correlated with metastasis, extracapsular spread, grade and stage. The correlation between TUNEL, p53 and Ki67 staining and survival probabilities, and the pathological grade, stage and metastasis spread of salivary malignancies makes this a highly effective tool in patient follow-up and prognosis.

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Section: Discussionmentioning

confidence: 99%

TUNEL – an efficient prognosis predictor of salivary malignancies

et al. 2007

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“…Our data indicate that tumors with activated Akt exhibit a 21 Several studies conducted on the possible prognostic value of apoptotic markers revealed varying results. While some studies report high levels of apoptosis to be associated with worse survival, [22][23][24] the majority fail to demonstrate an independent prognostic value. [25][26][27][28] In contrast, Tanaka et al 29 demonstrated that loss of apoptosis due to the expression of an apoptosis inhibitor (survivin) was an independent prognostic parameter in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Prognostic relevance of activated Akt kinase in node-negative breast cancer: a clinicopathological study of 99 cases

Schmitz

Otterbach

Callies³

et al. 2003

Mod Pathol

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Patients with lymphnode-negative breast cancer show a 10-year tumor recurrence rate of approximately 30%. Therefore, it is important to identify high-risk patients who would benefit from further adjuvant therapy. For this purpose, we examined the activation state of two kinases important in the regulation of cell proliferation and apoptosis in a series of 99 node-negative breast cancer cases with a mean follow-up of 10 years: Akt and extracellular regulated kinase (ERK1/2). The activation of Akt and ERK1/2 was investigated by immunohistochemistry using phospho-specific antibodies. The results were correlated with HER-2/neu expression, histological grading, receptor status, overall survival (OS) as well as with cell proliferation (Ki67 immunoreactivity, mitotic count) and tumor apoptosis assessed by TUNEL staining. Activation of Akt (pAkt) but not activation of ERK1/2 (pERK1/2) correlated with HER-2/neu overexpression (Po0.05) and was related to reduced tumor apoptosis (Po0.05). No association was found between pAkt or pERK1/2 with cell proliferation assessed by Ki67 and mitotic count (MC). Survival analysis of receptor status, HER2/neu expression, histological grading, MC and pAkt immunoexpression showed a significant correlation with decreased OS, but only pAkt reached statistical significance in the multivariate Cox regression analysis (P ¼ 0.015). Activation of Akt in node-negative breast cancer may indicate aggressive tumor behavior and may constitute an independent prognostic factor of OS. The determination of pAkt status may be of value in identifying high-risk patients, who would benefit from adjuvant therapy, and gives a rationale to investigate new therapy strategies by specific inhibition of the Akt signaling pathway in breast cancer.

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“…As alterações moleculares que são observadas nas células do paciente com câncer, começam a ser compreendidas e estão relacionadas com os mecanismos que regulam a divisão celular normal, a sobrevivência e a morte celular 17,18 . A morte celular programada, também chamada de apoptose, tem um papel importante na determinação do crescimento tumoral e sua agressividade 19 . Sendo assim, a apoptose é considerada um mecanismo celular intrínseco e regulado, através do qual há um controle entre a produção de novas células e a capacidade individual das células em se autodestruírem 20,21,22 .…”

Section: Introductionunclassified

“…Segundo O'Donavan et al 24 , a marcação da caspase-3 pode ser usada no controle da resposta aos tratamentos quimioterápicos quanto a possível resistência da droga, onde a diminuição da expressão pode indicar um mecanismo importante de sobrevivência celular em pacientes com câncer de mama 27,10 . Wu, Shao e Jiang 26 mostraram que o índice de apoptose é um fator prognóstico independente, mas Gonzáles-Cámpora et al 19 demonstraram que a estimativa da apoptose é um fator de prognóstico independente, assim como os índices de proliferação celular ou a expressão da proteína bcl-2 (inibidor da apoptose) ou p53 (indutor da apoptose). Sendo assim, a mensuração da proliferação e da apoptose podem promover um prognóstico real do comportamento tumoral 27 .…”

Section: Introductionunclassified

Avaliação da caspase-3 e Ki-67 como marcadores prognósticos nas neoplasias mamárias em cadelas

Terzian

Zuccari

Pereira

et al. 2007

Braz. J. Vet. Res. Anim. Sci.

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A apoptose e a proliferação celular possuem uma participação importante na tumorigênese, determinando o crescimento tumoral e consequentemente sua agressividade. O presente estudo teve como objetivo avaliar a ocorrência da apoptose associada a proliferação celular em neoplasias mamárias em cadelas e a elas a evolução clínica do paciente. Setenta animais foram submetidos à exérese cirúrgica do tumor, sendo este submetido ao diagnóstico histopatológico e marcação imuno-histoquímica para caspase-3 e Ki-67. Estes marcadores de apoptose e proliferação celular demonstraram grande expressão nas neoplasias malignas, principalmente nos carcinomas, considerado o mais maligno dos tumores. Estes resultados corroboram os dados da literatura e contribuem para um prognóstico tumoral criterioso que complementa a classificação tumoral existente proporcionando uma melhor e maior sobrevida devido a uma adequação do procedimento terapêutico de cada paciente.

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Apoptosis in Breast Carcinoma

Cited by 26 publications

References 41 publications

TUNEL – an efficient prognosis predictor of salivary malignancies

TUNEL – an efficient prognosis predictor of salivary malignancies

Prognostic relevance of activated Akt kinase in node-negative breast cancer: a clinicopathological study of 99 cases

Avaliação da caspase-3 e Ki-67 como marcadores prognósticos nas neoplasias mamárias em cadelas

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