An immunohistochemical study of cyclin D1 protein expression in laryngeal squamous cell carcinoma

Morshed, Kamal; Skomra, Danuta; Korobowicz, E; Szymański, Marcin; Polz‐Dacewicz, Małgorzata; Gołąbek, Wiesław

doi:10.1080/00016480601001957

Cited by 13 publications

(11 citation statements)

References 20 publications

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“…However, EGFR protein overexpression is a basis for FDA approved targeted chemotherapeutic strategies via monoclonal antibodies (cetuximab) and/or small tyrosine-kinase inhibitors (gefinitib, erotinib) [7]. Additionally, over activation of cell cycle control molecules, including cyclin D1 (CCND1 gene location: 11q13), leads to advanced disease, but there are controversial results regarding to its independent prognostic significance [8,9].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous over activation of EGFR, telomerase (h TERT), and cyclin D1 correlates with advanced disease in larynx squamous cell carcinoma: a tissue microarray analysis

Chrysovergis¹,

Gorgoulis

Giotakis³

et al. 2010

Med Oncol

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Overexpression of Epidermal Growth Factor Receptor (EGFR) and also of cell cycle control proteins, such as cyclin D1 is a frequent event in squamous cell carcinoma of the larynx (LSSC). Our aim was to correlate their protein levels with telomerase catalytic subunit (h-TERT) expression. Using tissue microarray technology, fifty-five paraffin embedded histologically confirmed primary LSSCs and also ten dysplastic lesions were cored at a diameter of 1.5 mm. Immunohistochemistry (IHC) was performed by the use of anti-EGFR, anti-cyclin D1, and anti-h TERT monoclonal antibodies. Chromogenic in situ hybridization (CISH) analysis was also applied using EGFR gene and chromosome 7 probes, respectively. EGFR, cyclin D1 and h-TERT protein overexpression was observed in 48/55 (87.2%), 19/55 (34.5%) and 21/55 (38.1%) carcinoma cases, respectively. EGFR protein expression was statistically associated with grade (P=0.01), and also with stage (P=0.001) of the examined tumors. Borderline statistical significance was assessed correlating overall cyclin D1 expression to h TERT expression (P=0.06). Simultaneous up regulation of the three proteins was established in 7/55 (12.7%) cases, correlated to the stage of the tumors (P=0.05). EGFR gene amplification was observed in 7/65 (10.7%) carcinomas and dysplasias, whereas chromosome 7 aneuploidy was detected in 4/65 (6.1%) of those cases.Simultaneous up regulation of EGFR, cyclin D1 and h TERT proteins correlates with advanced stage in LSCC. EGFR gene amplification and not only protein over expression maybe is the eligible criterion for targeted therapeutic strategies in those patients.

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Section: Introductionmentioning

confidence: 99%

Simultaneous over activation of EGFR, telomerase (h TERT), and cyclin D1 correlates with advanced disease in larynx squamous cell carcinoma: a tissue microarray analysis

Chrysovergis¹,

Gorgoulis

Giotakis³

et al. 2010

Med Oncol

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“…CyclinD1, G1 phase cyclin, is regulated by growth factors in the cell cycle. It can be combined with CDK4 or CDK6 to form complexes to promote cell proliferation, and lead to tumors when CyclinDl is expressed out of control[31]. In this study, the expression of genes EGFR, AKT, CDK-4, and CyclinD1 and the proteins AKT, p-AKT and CyclinD1 were found to show circadian rhythm on different dosing times.…”

Section: Discussionmentioning

confidence: 66%

Chronopharmacology and Mechanism of Antitumor Effect of Erlotinib in Lewis Tumor-Bearing Mice

Wang

Zhuang

et al. 2014

PLoS ONE

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The epidermal growth factor receptor (EGFR), a ubiquitously expressed receptor tyrosine kinase, is recognized as a key mediator of tumorigenesis in many human epithelial tumors. Erlotinib is tyrosine kinase inhibitor approved by FDA for use in oncology. It inhibits the intracellular phosphorylation of tyrosine kinase associated with the EGFR to restrain the development of the tumor. To investigate the antitumor effect of erlotinib at different dosing times and the underlying molecular mechanism via the PI3K/AKT pathway, we established a mouse model of Lewis lung cancer xenografts. The tumor-bearing mice were housed four or five per cage under standardized light-dark cycle conditions (light on at 7:00 AM, 500 Lux, off at 7:00 PM, 0 Lux) with food and water provided ad libitum. The mice were observed for quality of life, their body weight and tumor volume measured, and the tumor growth curves drawn. After being bled, the mice were sacrificed by cervical dislocation. The tumor masses were removed at different time points and weighed. The mRNA expression of EGFR, AKT, Cyclin D1 and CDK-4 were assayed by quantitative real-time PCR (qRT-PCR). Protein expression levels of AKT, P-AKT and Cyclin D1 were determined by Western blot analysis. The results suggest that erlotinib has a significant antitumor effect on xenografts of non-small cell lung cancer in mice, and its efficacy and toxicity is dependent on the time of day of administration. Its molecular mechanism of action might be related to the EGFR-AKT-Cyclin D1-CDK-4 pathway which plays a crucial role in the development of pathology. Therefore, our findings suggest that the time of day of administration of Erlotinib may be a clinically important variable.

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“…The over-expression of cyclin Dl and its association with clinico-pathological features in LSCC has been analysed in various studies. [20][21][22][23] Although cyclin D1 as per our analysis showed no significant difference in the intensity as the T-stage, N-stage or grade of tumor advances, it showed statistically significant intense expression in tumors with ECS (92.3%) as well as PNI (94.7%) (p<0.0001).…”

Section: Cyclin D1mentioning

confidence: 85%

“…In support to the present finding various studies in literature also represented no correlation with survival and expression of cyclin D1. 23,26,27 Literature stated that intense cyclin D1 expression has been associated with increased risk of death and its over-expression has been correlated very well with bad prognosis among laryngeal tumors. 3,10,[28][29][30] Cyclin D1 plays an important role in cell cycle and that might be the reason for worse prognosis of its over-expression.…”

Section: Cyclin D1mentioning

confidence: 99%

Expression of proliferation markers in laryngeal squamous cell carcinoma: an association with clinico-pathological factors and treatment outcomes

Iype

Balakrishna

Subhadradevi

et al. 2020

Int J Otorhinolaryngol Head Neck Surg

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Background: The study was done with the objective to study the expression of epidermal growth factor receptor (EGFR), cyclin D1 and Ki-67 in laryngeal squamous cell carcinoma and to assess the correlation of all three proliferation markers with various clinic-pathological parameters, the treatment outcomes as well as survival.Methods: We prospectively evaluated the surgical specimens of 72 laryngeal squamous cell carcinoma (LSCC) patients, treated with primary surgery and post-operative adjuvant therapy. Tumor tissue samples were analysed for the expression of EGFR, cyclin D1 and Ki-67 markers and analysis were done by immune-histochemistry and western blot test. Results: EGFR showed significant expression in 67.6% and was insignificant in 31.9% patients in our analysis of 72 tumor samples. Cyclin D1 showed intense expression in 43%, and was insignificant in 57% patients. Ki-67 was intensely expressed in 43% patients. There was no correlation between expression of these markers with age, T-stage and N-stage. However, all the three markers showed significantly intense expression in tumours with extra capsular disease as well as perineural invasion (PNI) both of which are features of invasiveness of the tumor.Conclusions: Estimation of biomarkers such as EGFR, cyclin Dl, and Ki-67 could be beneficial in predicting tumor aggressiveness, prognosis and survival in LSCC patients. Thus, all the three proliferation markers can be categorized as markers of invasiveness. Combination of proliferation markers-EGFR, cyclin D1 and Ki-67 is useful pre-operatively in planning surgical strategies so as to decide a more radical approach for the resection of the primary as well as neck dissection.

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An immunohistochemical study of cyclin D1 protein expression in laryngeal squamous cell carcinoma

Cited by 13 publications

References 20 publications

Simultaneous over activation of EGFR, telomerase (h TERT), and cyclin D1 correlates with advanced disease in larynx squamous cell carcinoma: a tissue microarray analysis

Simultaneous over activation of EGFR, telomerase (h TERT), and cyclin D1 correlates with advanced disease in larynx squamous cell carcinoma: a tissue microarray analysis

Chronopharmacology and Mechanism of Antitumor Effect of Erlotinib in Lewis Tumor-Bearing Mice

Expression of proliferation markers in laryngeal squamous cell carcinoma: an association with clinico-pathological factors and treatment outcomes

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