Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the oral cavity: clinicopathological and prognostic significance

Vicente, Juan Carlos de; Herrero-Zapatero, A; Fresno, Manuel; López-Arranz, Juan Sebastián

doi:10.1016/s1368-8375(01)00060-4

Cited by 82 publications

(80 citation statements)

References 27 publications

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“…In the present study, we analysed non-phosphorylated Rb and found, as predicted, lower expression in the cancerous stage, in accordance with other studies (17). Overexpression of cyclin D1 has been reported in oral cancer (18) and even in premalignant lesions (16) as being related to poor prognosis in the majority of studies (18)(19)(20). However, a study attempting to explain this overexpression by analysing two polymorphisms, A870G and C1722G (21), did not yield conclusive results.…”

Section: Discussionsupporting

confidence: 91%

Differences in the expression of five senescence markers in oral cancer, oral leukoplakia and control samples in humans

Bascones-Martínez¹,

López-Durán²,

Cano‐Sánchez³

et al. 2012

Oncology Letters

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Abstract. Oncogene-induced senescence (OIS) may be a response to oncogenic activation, acting as a natural barrier against carcinogenesis at a premalignant stage. Thus, numerous cells in premalignant lesions enter senescence, but none or few in malignant tumours. This event could be due to the loss of senescence pathway effectors, including p16 (INK4a)-pRb or ARF-p53. The aim of this study was to characterize and compare the expression of certain senescent markers between oral precancer and cancer tissue samples. The expression of cyclin D1, Rb, maspin, p53 and mouse double minute 2 (MDM2) was analyzed in 20 paraffin-embedded tissue samples of normal oral mucosa (NOM), 14 samples of oral leukoplakia without dysplasia (OLD-), 11 samples of leukoplakia with dysplasia (OLD+) and 15 samples of oral squamous cell carcinoma (OSCC) by immunohistochemistry in tissue arrays. The expression of p16-pRb pathway markers, cyclin D1, maspin and Rb, was more frequent in OLD+ samples than in OSCC samples, although a statistical significance was only observed for maspin (P=0.036). Cyclin D1 expression was also significantly more frequent in OLD-samples vs. NOM samples. For the ARF-p53 pathway, the expression of p53 and MDM2 was significantly more frequent in the OLD-samples compared to in the NOM ones. These findings may indicate a role for cellular senescence in oral carcinogenesis, considering maspin as a reliable senescence marker and prognostic factor in oral premalignant lesions.

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Section: Discussionsupporting

confidence: 91%

Differences in the expression of five senescence markers in oral cancer, oral leukoplakia and control samples in humans

Bascones-Martínez¹,

López-Durán²,

Cano‐Sánchez³

et al. 2012

Oncology Letters

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“…In our earlier study, Vora et al [19] also observed overexpression of cyclin D1 in tongue carcinoma. Similar to our results, Carlos de et al [20] and Bova et al [13] have reported higher accumulation of cyclin D1 in tongue cancer. Overexpression of cyclin D1 has been associated with a more aggressive tumor phenotype and reduced survival in patients with operable HNSCC from different anatomical sites [21,22,23].…”

Section: Details Of Clinicopathological Parameters and Their Associatsupporting

confidence: 93%

Identification of site-specific prognostic biomarkers in patients with oral squamous cell carcinoma

Trivedi¹,

Tankshali²,

Goswami³

et al. 2011

neo

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The purpose of the present study was to identify site-specific prognostic biomarkers in patients with oral squamous cell carcinoma (OSCC). For this purpose, Epidermal growth factor receptor (EGFR), Stat3, H-ras, c-myc, p53, cyclin D1, p16, Rb and Bcl-2 were localized immunohistochemically in buccal mucosa carcinoma (n=74) and tongue carcinoma (n=61) patients. Expression of markers was compared between buccal mucosa and tongue carcinoma and assessed for their prognostic value in site-specific manner. On comparison, only cyclin D1 showed significant difference in expression with higher accumulation in tongue tumors (r=+0.177, p=0.039). Moreover, univariate survival analysis showed that in buccal mucosa patients, loss of p16 and overexpression of H-ras were significant prognosticators for relapse-free survival (RFS) and overall survival (OS), respectively. However, in Cox multivariate analysis, they lost their significance after adjusting for significant clinicopathological parameters. On the other hand, in tongue cancer patients, Cox multivariate analysis showed that for RFS, Stat3 and c-myc, and for OS, Stat3, Bcl-2 and p53 were significant prognosticators after adjusting for significant confounding factors. Our findings indicated that buccal mucosa and tongue carcinoma exhibit different biological behavior which is reflected in prognosis. Therefore, this approach might be helpful to precisely identify patients for more effectively tailored treatment strategy.

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“…Epidermal growth factor receptor (EGFR) is a potent membrane-bound tyrosine kinase that promotes cellular proliferation, and overexpression of EGFR has been reported to be of prognostic value in head and neck carcinoma (5). Cyclin D1 is a cell cycle regulatory molecule in the G 1 to S-phase control and has been shown to be associated with increased lymph node stage in anterior tongue cancer (6,7). Ki-67 is a proliferation marker, and the Ki-67 index has been reported to be correlated with poor prognosis in oral tongue squamous cell carcinoma (8).…”

Section: Introductionmentioning

confidence: 99%

Predictive Markers for Late Cervical Metastasis in Stage I and II Invasive Squamous Cell Carcinoma of the Oral Tongue

Lim

Zhang

Ishii

et al. 2004

Clinical Cancer Research

241

200

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Purpose: Patients with oral tongue carcinoma treated by intraoral excision only should be followed up carefully for cervical lymph node metastasis and salvaged immediately if found, because some patients have a more aggressive clinical course. The purpose of this study was to find useful markers for predicting late cervical metastasis in patients with stage I and II invasive squamous cell carcinoma of the oral tongue.Experimental Design: We investigated clinicopathologic factors and immunohistochemical biomarkers predicting late cervical metastasis in surgical specimens from 56 patients with T 1-2 N 0 M 0 invasive squamous cell carcinoma of the oral tongue who did not undergo elective neck dissection. Histopathologic factors including tumor thickness, mode of invasion, Broders grade, total score of three different malignancy grading systems, eight other clinicopathologic parameters, and immunohistochemical expression of p53, cyclin D1, Ki-67, epidermal growth factor receptor, microvessel density, cyclooxygenase-2, MUC1, laminin-5 ␥2, E-cadherin, and ␤-catenin were examined. All of the clinicopathologic factors and immunohistochemical expression of biomarkers were compared in terms of survival.Results: In the univariate analysis, tumor thickness (P ‫؍‬ 0.009), Broders grade (P ‫؍‬ 0.017), nest shape (P ‫؍‬ 0.005), mode of invasion (P < 0.001), Anneroth score (P ‫؍‬ 0.029), Bryne score (P < 0.001), and E-cadherin expression (P ‫؍‬ 0.003) were correlated with late cervical metastasis. Multivariate analysis on late cervical metastasis revealed that tumor thickness >4 mm, mode of invasion grade 3 or 4, and E-cadherin expression were independent factors. Late cervical metastasis was the only prognostic factor for overall survival (P ‫؍‬ 0.002).Conclusions: Our results indicate that patients with stage I and II invasive squamous cell carcinoma of the oral tongue with tumor thickness >4 mm, mode of invasion grade 3 or 4, and low expression of E-cadherin should be considered a high-risk group for late cervical metastasis when a wait-and-see policy for the neck is adopted.

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Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the oral cavity: clinicopathological and prognostic significance

Cited by 82 publications

References 27 publications

Differences in the expression of five senescence markers in oral cancer, oral leukoplakia and control samples in humans

Differences in the expression of five senescence markers in oral cancer, oral leukoplakia and control samples in humans

Identification of site-specific prognostic biomarkers in patients with oral squamous cell carcinoma

Predictive Markers for Late Cervical Metastasis in Stage I and II Invasive Squamous Cell Carcinoma of the Oral Tongue

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