Proliferation markers in tumours: interpretation and clinical value.

Diest, Paul J. van; Brugal, G.; Baak, J. P. A.

doi:10.1136/jcp.51.10.716

Cited by 187 publications

(148 citation statements)

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“…2 However, the growth fraction, i.e., the proportion of cells committed to the cycle, may be easily assessed by Ki-67 or MIB-1 antibodies, which identify antigens expressed in the G 1 , S and G 2 phases of the cell cycle. 3,4 In particular, SPF, besides being the gold standard technique, 5 can be assessed by immunohistochemical detection of PCNA, a 36 kDa auxiliary protein of DNA polymerase-delta nuclear protein involved in DNA synthesis, with a relevant correlation to the proliferative state of the cell. 6 Besides the relevance of studies on several markers, it was mandatory to investigate the risk factors of continued use of tobacco, alcohol misuse, diet and viral infections.…”

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confidence: 99%

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks

Muzio

D’Angelo

Procaccini

et al. 2005

Intl Journal of Cancer

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Our aim was to evaluate in oral squamous cell carcinoma (OSCC) the relationship between some cell cycle markers and HPV infection, conditionally to age, gender and certain habits of patients, and to assess the ability of fuzzy neural networks (FNNs) in building up an adequate predictive model based on logic inference rules. Eighteen cases of OSCC were examined by immunohistochemistry for MIB-1, PCNA and survivin expression; presence of HPV DNA was investigated in exfoliated oral mucosa cells by nested PCR (nPCR, MY09-MY11/GP5-GP6), and HPV genotype was determined by direct DNA sequencing. Data were analyzed by traditional statistics (TS) and FNNs. HPV DNA was found in 9/18 OSCCs (50.0 %) without any significant higher risk of HPV infection with respect to the sociodemographic variables considered ( p > 0.2), apart from tobacco smoking, reported in 44.4% of OSCC HPV-positive vs. 100% HPV-negative subjects ( p = 0.029). Regarding cell cycle markers, TS and FNN revealed that survivin was expressed significantly more in HPV-negative than in HPVpositive OSCC [root mean-square error (RMSE) = 5.89 3 10 -6 , % predicted 100.0]; furthermore, smoking played a protective role for survivin expression in HPV-positive cases (OR = 0.019, 95%CI 0.001-0.723, RMSE = 0.20, % of prevision 94.4). FNN, although on a small sample size, allowed us to confirm data by TS and to hypothesize a different cell cycle pattern for HPV-positive vs. HPV-negative OSCC. In the latter cases, the relevance of apoptotic vs. proliferative markers suggested that they may be related to the different supposed outcome of HPV-negative OSCC and that HPV may have a protective role in the expression level of survivin, especially in tobacco smokers. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; survivin; oral squamous cell carcinoma; fuzzy neural network; carcinogenesis OSCC is rapidly increasing in incidence and represents the most frequent malignant oral tumor. The incidence of metastasis depends on the degree of cellular differentiation, deep invasion and site of the primary tumor; however, outcome is difficult to predict if only standard clinicopathologic parameters are taken into account. Biologic markers that can help to identify lesions with an aggressive phenotype and worse prognosis need to be identified.Since the majority of human neoplasms are characterized by an imbalance of the regulatory cell cycle control processes, the study of OSCC using the expression of proteins involved in the critical checkpoints of cell apoptosis and growth starts by elucidating the processes of carcinogenesis and appears to have good prognostic value. 1 Indeed, we know that apoptosis, or programmed cell death, and its suppression are involved in the carcinogenesis of several tumors; this process, mediated by caspases and cysteine proteinases present as proenzymes, is inhibited by several proteins, such as those of the Bcl-2 and IAP families. Survivin is an IAP protein, which is abundantly expressed in most solid and hematologic malignancies but undetectable in ...

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confidence: 99%

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks

Muzio

D’Angelo

Procaccini

et al. 2005

Intl Journal of Cancer

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“…Correlation between high proliferative activity and worse prognosis for laryngeal and head and neck tumors has shown, particularly for neoplasms invading structures located adjacently to the tumor's site of origin 4,5,8,9 . This study aims to relate the immunohistochemical expression of gene p53 and antibody Ki-67 to established prognostic factors (age, histological grade, lymph node status, and disease staging) in patients with laryngeal epidermoid carcinoma.…”

Section: Introductionmentioning

confidence: 99%

“…Cell proliferation is also seen as a fundamental biologic mechanism in oncogenesis 8 and in the detection of cell growth fraction markers such as antibody Ki-67, used as a prognostic factor in a wide variety of tumors [9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Valor prognóstico da correlação imunoistoquímica do Ki-67 e p53 em carcinomas epidermóides da laringe

Rodrigues

Motta

Machado

et al. 2008

Rev. Bras. Otorrinolaringol.

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Prognost ic histological factors may contribute to determine the evolution of this neoplasia. Aim: To correlate p53 and Ki-67 immunohistochemical expression with age, histological degree, lymph node involvement and pathological staging in patients with laryngeal epidermoid carcinomas. Methods:We assessed thirty consecutive cases of laryngeal epidermoid carcinomas submitted to immunohistochemistry to check the expression of p53 e Ki-67 antibodies. Results: Mean age was of 56.2 years and the immunoexpression of the markers was observed in the group with more than 50 years of age, especially that o the ki-67 antibody (p=0.032). There was no relation between p53 and Ki-67 with lymph node involvement. Ki-67 was expressed in 70% of the high histology level cases and in 80% in the low histology ones; while p53 was of 70% only in the high level cases. Pathology staging showed that in the group of advanced carcinomas, p53 expression was of 61.5%, while Ki-67 proved positive for the early cases (100%) and advanced (73.1%). Conclusion: There were no significant differences between p53 and Ki-67 immunoexpression in laryngeal epidermoid carcinoma, except in the group of patients with more than 50 years of age, when Ki-67 expression was significantly higher.

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“…Essa proteína não está envolvida no sistema de reparação do DNA, e sua expressão restringe-se aos compartimentos proliferativos dos tecidos. Adicionalmente, o Ki-67 não sofre influências marcantes da fixação e do processamento histológicos ou da diluição do anticorpo (6,10,19,28,29) . Nossos resultados demonstraram que não houve diferença estatisticamente significativa entre os dois grupos analisados (p = 0,72), fato este também verificado por Donofrio et al (3) , que não encontraram correlação entre presença de HPV e índices aumentados de proliferação celular em lesões cancerizáveis (displasias leves, moderadas e severas) e OSCCs microinvasivos.…”

Section: Discussionunclassified

Análise comparativa da proliferação celular entre carcinomas de células escamosas orais HPV-positivos e HPV-negativos

Rocha¹,

Souza²,

Pinto³

2007

J. Bras. Patol. Med. Lab.

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Introdução: O carcinoma de células escamosas oral (OSCC) representa a neoplasia maligna mais freqüente em boca, e, entre os agentes etiológicos implicados, o papilomavírus humano (HPV) tem sido extensivamente estudado nos últimos anos. Objetivo: Analisar comparativamente os índices de proliferação celular em OSCCs HPV-negativos e HPV-positivos. Material e método: A amostra consistiu em 11 casos de OSCCs HPV-positivos (10 infectados por HPV-18 e um por HPV-16 e 18) e 13 HPVnegativos, previamente analisados quanto à presença ou ausência, bem quanto à tipagem viral por proteína C reativa (PCR) (primers GP5+/GP6+) e hibridização dot blot, respectivamente. No método imunoistoquímico utilizou-se a técnica da estreptoavidina-biotina, com anticorpo para a proteína nuclear Ki-67. Resultados: O teste estatístico não-paramétrico de Mann-Whitney revelou que não houve diferença estatisticamente significativa entre os grupos HPV-positivo e HPV-negativo (p = 0,72). Discussão: Os estudos semelhantes a estes são poucos e não são concordantes em demonstrar maior atividade proliferativa tumoral nos casos HPV-positivos em relação aos HPV-negativos, seja através da análise da expressão de proteínas relacionadas ao ciclo celular, seja na análise direta da fração proliferativa tumoral. Conclusão: Não houve diferença no índice de proliferação celular entre os grupos de OSCCs HPV-positivo e HPV-negativos. abstract resumo Background: Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor in the mouth, and the human papillomavirus (HPV) has been hardly studied as a possible etiologic agent. Objectives: The aim of this study was to compare the rates of cell proliferation in HPV-positive and HPV-negative OSCC, using the immunohistochemical antibody Ki-67. Material and method: The sample consisted of 11 cases HPV-positive OSCC (10 cases infected with HPV-18 and 1 case infected with HPV-16 and 18) and 13 cases HPV-negative OSCCs, previously analyzed regarding the presence or absence of HPV, as well as the viral type, using PCR (primers GP5+/GP6+) and dot blot hybridization, respectively. Immunohistochemical study was performed by streptoavidin-biotin technique with antibody against nuclear protein

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Proliferation markers in tumours: interpretation and clinical value.

Cited by 187 publications

References 135 publications

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks

Expression of cell cycle markers and human papillomavirus infection in oral squamous cell carcinoma: Use of fuzzy neural networks

Valor prognóstico da correlação imunoistoquímica do Ki-67 e p53 em carcinomas epidermóides da laringe

Análise comparativa da proliferação celular entre carcinomas de células escamosas orais HPV-positivos e HPV-negativos

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