Cyclin D1 and p27 Expression as Prognostic Factor in Papillary Carcinoma of the Thyroid: Association with Clinicopathological Parameters

Pešutić-Pisac, Valdi; Punda, Ante; Glunčić, Ivo; Bedeković, Vladimir; Pranić-Kragić, Anka; Kunac, Nenad

doi:10.3325/cmj.2008.5.643

Cited by 36 publications

(29 citation statements)

References 24 publications

(26 reference statements)

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“…All of the tumors chosen for this study were cyclin D1 positive and these results are consistent with a previous study conducted by Saiz et al 19 Overexpression of cyclin D1 has been identified as a predictor of lymph node metastasis in papillary thyroid carcinoma; 7,8,10 however, we found no significant correlation between its overexpression (more than 25% of positively staining tumor cells) and lymph node metastasis (P ¼ 0.061). The isolated glands, which are defined as individual glands of papillary thyroid carcinoma cells found in the extra-tumoral region, are distinctive histological features of papillary thyroid carcinoma and should not be confused with the tumor multifocal foci.…”

Section: Discussionsupporting

confidence: 67%

“…In some studies, cyclin D1 expression was not an independent predictive factor for lymph node metastasis during multivariate analysis, although it has been found to be associated with lymph node metastasis in univariate analysis. 10,11 BRAF V600E mutation has frequently been detected in papillary thyroid carcinoma, but has not been identified in benign thyroid lesions. 12,13 In Korea, the prevalence of the BRAF V600E mutation accounts for up to 87% of all cases of papillary thyroid carcinoma.…”

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confidence: 99%

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Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma

et al. 2010

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Although many attempts have been made to predict the occurrence of lymph node metastases from papillary thyroid carcinoma, there are currently no reliable means to accurately predict cervical nodal metastasis. In this study, we present a novel prediction system for the lymph node metastasis based on the histological and cyclin D1 staining features. The frequency of lymph node metastases from a series of 210 papillary thyroid carcinomas was analyzed according to the clinicopathological variables, cyclin D1 staining patterns and BRAF V600E mutation in tumor tissue. A total of 113 (54%) patients had lymph node metastasis. Cyclin D1 was constantly expressed at the invasive tumor front and revealed well-defined isolated glands of tumor cells in the extratumoral region (isolated glands) and laterally spreading tubular growth along the fibrous septa around the invasive front of the tumor (lateral tubular growth). Upon univariate analysis, an age of less than 45 years (Po0.001), tumor size of 10 mm or more (Po0.001), non-follicular variant (P ¼ 0.005), invasive growth pattern (P ¼ 0.007), extrathyroid extension (P ¼ 0.006), isolated glands (Po0.001), lateral tubular growth (Po0.001) and tumor multiplicity (P ¼ 0.005) predicted lymph node metastasis, whereas BRAF V600E mutation did not. Upon multivariate analysis, age (P ¼ 0.001, odds ratio (OR) ¼ 5.146), tumor size (P ¼ 0.034, OR ¼ 3.119), isolated glands (Po0.001, OR ¼ 21.042) and lateral tubular growth (Po0.001, OR ¼ 24.652) were found to be strong independent predictors of lymph node metastasis. Cyclin D1 staining of papillary thyroid carcinoma is very useful for identifying the intrathyroidal spreading or multifocality of the tumors. Tumor growth patterns verified by cyclin D1 staining can be used for the identification of papillary thyroid carcinomas with metastatic potential.

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Section: Discussionsupporting

confidence: 67%

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confidence: 99%

Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma

et al. 2010

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“…PTCs with increased cyclin D1 and decreased p27 expression have been linked to metastatic nodal disease [25][26][27][28][29]. In a previous study, HBME-1 expression has been linked to the prediction of lymph node metastasis even within the RASlike PTCs [29].…”

Section: Discussionmentioning

confidence: 97%

The Value of HBME-1 and Claudin-1 Expression Profile in the Distinction of BRAF-Like and RAS-Like Phenotypes in Papillary Thyroid Carcinoma

et al. 2016

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This study compared the expression profile of HBME-1 and claudin-1 in 90 papillary thyroid carcinomas (PTCs) with respect to the tumor architecture and invasive growth as reflected in 46 BRAF-like, 31 non-invasive RAS, and 13 invasive RAS-like phenotypes. Individual tumors were given an expression score (max 300) by multiplying the percent positive tumor cells by the intensity score (range 0-3). The higher expression of HBME-1 and claudin-1 distinguished BRAF-like phenotype from RAS-like phenotype. The same correlation was also retained for both markers when comparing BRAF-like phenotype with non-invasive and invasive RAS-like phenotypes. The expression scores and positivity rates for both markers did not yield any statistical difference among BRAF-like PTCs. Except the higher positivity rate of HBME-1, invasive RAS-like tumors were not statistically different than their non-invasive counterparts with respect to the positivity rate of claudin-1 and the expression scores of both markers. A central lymph node dissection or selective lymph node sampling was available in 20 specimens. The absence of claudin-1 expression has not been a feature of lymph node metastasis in this series. Despite the limited number of nodal sampling, BRAF-like phenotype and claudin-1 positivity status have been considered the best determinants of positive predictive value and negative predictive value in the prediction of lymph node metastasis among variables, respectively. Adoption of the simplified architectural classification approach to PTCs showed distinct biomarker expression profile in this series; however, immunohistochemistry for HBME-1 and claudin-1 does not seem to be useful in the distinction of invasive RAS-like PTCs from their non-invasive counterparts. Given the overlapping molecular signatures within the RAS-like phenotype, further studies with additional biomarkers are still needed to identify distinct protein expression signatures of non-invasive RAS-like phenotype as this diagnostic category still remains a surgical diagnosis at this time.

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“…Cyclin-D1 in tumors was labeled as negative if <10%, moderately positive between 10% and 50%, and strongly positive if >50%, tumor cells expressed the antigen. [7,8] Assessment of tumor response was done by clinical examination, radiologic investigations (computed tomography [CT]-scan) 4-6 weeks after completion of treatment. Biopsy or fine needle aspiration cytology to determine pathologic response was not performed routinely; it was done only in case of partial response (PR)/suspected lesion to confirm the presence of disease.…”

Section: Methodsmentioning

confidence: 99%

Prognostics of Cyclin-D1 expression with chemoradiation response in patients of locally advanced oral squamous cell carcinoma

Khan¹,

Gupta²,

Husain³

et al. 2014

J Can Res Ther

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Cyclin D1 and p27 Expression as Prognostic Factor in Papillary Carcinoma of the Thyroid: Association with Clinicopathological Parameters

Cited by 36 publications

References 24 publications

Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma

Unique patterns of tumor growth related with the risk of lymph node metastasis in papillary thyroid carcinoma

The Value of HBME-1 and Claudin-1 Expression Profile in the Distinction of BRAF-Like and RAS-Like Phenotypes in Papillary Thyroid Carcinoma

Prognostics of Cyclin-D1 expression with chemoradiation response in patients of locally advanced oral squamous cell carcinoma

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