Underexpression of p27/Kip in Thyroid Papillary Microcarcinomas With Gross Metastatic Disease

Khoo, Mark L. C.; Freeman, Jeremy L.; Witterick, Ian J.; Irish, Jonathan C.; Rotstein, Lorne; Gullane, Patrick; Sylvia, L.

doi:10.1001/archotol.128.3.253

Cited by 56 publications

(34 citation statements)

References 21 publications

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“…[19][20][21] Our data showed that cyclin D1 expression is associated with lymph node metastasis, but not with macrometastasis or lateral node metastasis. And it failed to be independent predictive factor for lymph node metastasis, probably because of its strong association with tumor size (Po0.001).…”

Section: Discussionmentioning

confidence: 56%

“…However, to our knowledge, there have been few studies of the predictive factors for lymph node metastasis in papillary microcarcinomas, except for expression of cyclin D1 and p27, which were reported to be associated with lymph node metastasis. [19][20][21] In the present study, we investigated the predictive factors of lymph node metastasis in a large series of papillary microcarcinomas by analyzing clinicopathological variables, including patient age, tumor size (Z5 vs o5 mm), extrathyroidal extension, multifocality, histological subtype, sclerosis and encapsulation, expression of S100A4, cyclin D1, p27 and MUC1 and presence of the BRAF V600E mutation.…”

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confidence: 99%

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S100A4 expression is associated with lymph node metastasis in papillary microcarcinoma of the thyroid

et al. 2008

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The detection of papillary microcarcinomas of the thyroid is increasing due to frequent use of ultrasound and fine-needle aspiration biopsy. Although most of the papillary microcarcinomas remain quiescent and follow an indolent clinical course, some behave aggressively and metastasize early, giving rise to clinically significant disease. There have been few studies concerning factors predictive of lymph node metastasis in papillary microcarcinomas. We analyzed the expression of S100A4, cyclin D1, p27 and MUC1, the presence of the BRAF V600E mutation and the clinicopathological features of the tumors, including patient age, tumor size (Z5 vs o5 mm), extrathyroidal extension, multifocality, histological subtype, sclerosis and encapsulation, in a series of 198 papillary microcarcinomas in relation to lymph node metastasis to determine the predictive factors of lymph node metastasis. On univariate analysis, tumor size of 5 mm or more, extrathyroidal extension, multifocality, sclerosis and the expression of S100A4 and cyclin D1 predicted lymph node metastasis, whereas patient age, expression of p27 and MUC1 and the BRAF V600E mutation did not. Moreover, tumor size 5 mm or more, multifocality and expression of S100A4, especially its strong expression in the invasive fronts, were significantly associated with macrometastasis and lateral node metastasis. On multivariate analysis, multifocality and expression of S100A4 were found to be common independent predictive factors of lymph node metastasis, macrometastasis and lateral node metastasis. In conclusion, S100A4 expression in papillary microcarcinomas may indicate the presence of nodal metastasis. Thus, S100A4 immunohistochemistry may be valuable for predicting metastatic potential in papillary microcarcinomas.

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Section: Discussionmentioning

confidence: 56%

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confidence: 99%

S100A4 expression is associated with lymph node metastasis in papillary microcarcinoma of the thyroid

et al. 2008

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“…The BRAF V600E mutation has been shown to be associated with aggressive clinical behaviors of PTC by some investigators [37]; however, the evidence is still inconclusive, with contradictory reports [38]. Other molecular markers being investigated include cell-cycle regulators p27, p21, and cyclin D1 and immunohistochemical markers such as CEACAM-1 (carcinoembryonic antigenrelated cell adhesion molecule 1), OPN (osteopontin), and E-Cadh (E-cadherin) [39,40]. None of these markers have reached wide acceptance in clinical practice so far, including BRAF.…”

Section: Microrna In Staging and Prognosticationmentioning

confidence: 99%

MicroRNA Expression Profiles in the Management of Papillary Thyroid Cancer

et al. 2014

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Papillary thyroid cancer (PTC) is the major contributor to the dramatically increasing incidence of thyroid cancer. Low-risk PTC shows the most rapid rate of increase because of changing trends in neck imaging and the use of fine needle aspiration to investigate thyroid nodules. The need for a paradigm shift in the management of these patients, to provide personalized treatment and surveillance plans, has led to the focus on molecular biomarker research. MicroRNAs (miRNAs) compose a class of molecules with promising applications for every stage of PTC management, including diagnosis, prognosis, treatment, and surveillance. Although most of the miRNA studies are currently preclinical, given the rapid progress of scientific discovery, clinical trials will not be far away.Thyroid clinicians will be expected to have good insights into the current status of PTC-related molecular translational research.This article focuses on the potential roles of miRNA in PTC management in the context of contemporary recommended clinical practice.

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“…We also investigated p27 expression in this group of microcarcinomas and found it to be expressed in 63.4% of cases, confi rming the previously described fi nding that lymph node metastases showed a statistically signifi cant correlation with cyclin D1 expression and p27 non-expression (p=0.093) (Table 3). Similarly, Khoo et al report on a decreased level of p27 expression in papillary microcarcinomas with lymph node metastases as compared with those without lymph node metastases 27 . Th ese results confi rmed the importance of evaluating p27, cyclin D1 and RET expression, suggesting their potential usefulness in the evaluation of microcarcinoma behavior.…”

Section: Discussionmentioning

confidence: 84%

Cyclin D1, RET and p27 Expression in Papillary Thyroid Microcarcinoma

Barić

Marković

Eterović

et al. 2017

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SUMMARY -Th e aim of the study was to determine the infl uence of RET, p27 and cyclin D1 on regional lymph node metastases in papillary microcarcinoma. Th e analysis included 70 patients with papillary thyroid microcarcinoma that underwent surgery at Split University Hospital Center between 1999 and 2001. Immunohistochemistry was performed on formalin-fi xed, paraffi n-embedded tissue by the RET, p27 and cyclin D1 antibodies. Quantifi cation was based on the intensity and distribution of nuclear staining, dividing tumors into those that showed expression (expressors) and those that showed no expression (non-expressors). Univariate analysis using χ²-test and Fisher exact test was performed with the level of statistical signifi cance set at p<0.05. Th ere was no statistically signifi cant diff erence in the incidence of metastases according to the expression or non-expression of RET mutation (χ²-test: p=0.459; Fisher exact test: p=0.672). Among 25 cases with cyclin D1 expression, 6 had metastases, whereas only 2 of 45 cases with no cyclin D expression had metastases (χ²-test: p=0.014; Fisher exact test: p=0.021), indicating that the expression of cyclin D1 is not crucial for the development of metastases in lymph nodes. In contrast, analysis of p27 expression showed it to be signifi cantly associated with lymph node metastasis because 3 of 45 patients with p27 expression had metastases, indicating a statistically signifi cant correlation between p27 expression and lymph node metastases (χ²-test: p=0.093; Fisher exact test: p=0.124). Th is study confi rmed the importance of the evaluation of RET, p27 and cyclin D1 expression and demonstrated the validity of their application in the assessment of microcarcinoma behavior.

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Underexpression of p27/Kip in Thyroid Papillary Microcarcinomas With Gross Metastatic Disease

Abstract: Our results suggest that p27 immunohistochemical analysis may be a valuable diagnostic tool in predicting aggressive potential in PMCs.

Cited by 56 publications

References 21 publications

S100A4 expression is associated with lymph node metastasis in papillary microcarcinoma of the thyroid

S100A4 expression is associated with lymph node metastasis in papillary microcarcinoma of the thyroid

MicroRNA Expression Profiles in the Management of Papillary Thyroid Cancer

Cyclin D1, RET and p27 Expression in Papillary Thyroid Microcarcinoma

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