Immunohistochemical Expression of Bcl-2, Ki-67, and p21 in Patients with Papillary Thyroid Cancer

The thyroid cancer had an increasing frequency during the last decades mostly related to better and accessible detection methods. The papillary type has the major epidemiologic impact. We present a case with mixed symptoms before surgery, a rare combination of both thyrotoxicosis and thyroid malignancy and an unusual pathologic report in a 56-year-old female known with total hysterectomy at age of 42, diagnosed with toxic goiter 2 years ago and under intermittent therapy with thiamazol. She presented for unspecific hot flashes and palpitation at gynaecology and she was referred for endocrine evaluation that revealed unspecific cervical compression complains, and a large goiter. The Thyroid-Stimulating Hormone was normal under thiamazol and so were the thyroid antibodies and calcitonin. The computed tomography pointed an isthmus and left lobe nodule of maximum 7.28 cm with mass effect on trachea. Total thyroidectomy was performed without any significant complications. The patient was hospitalised for 4 days (less than 48 hours postoperatively). The pathological report showed a papillary thyroid cancer (stage III) with oxyphil variant and an insular and solid pattern component. A high proliferative index is detected by vessels invasion and a ki-67 of 15 %. She received radioiodine therapy and then she started suppression levothyroxine treatment. The insular and oxyphilic pattern as well as the large tumour size of 6 cm suggest a severe prognosis. On the other hand, it is still a matter of debate whether non-autoimmune hyperthyroidism and solid pathologic features subscribe to the hypothesis of an aggressive cancer phenotype. Lifelong follow up is needed.

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Immunohistochemical Expression of Estrogen Receptor-α and Progesterone Receptor in Patients with Papillary Thyroid Cancer

European Thyroid Journal ◽

10.1159/000452488 ◽

2016 ◽

Vol 5 (4) ◽

pp. 224-230 ◽

Cited By ~ 13

Author(s):

Giacomo Sturniolo ◽

Carles Zafon ◽

Mariacarla Moleti ◽

Josep Castellví ◽

Francesco Vermiglio ◽

...

Keyword(s):

Estrogen Receptor ◽

Thyroid Cancer ◽

Progesterone Receptor ◽

Papillary Thyroid Cancer ◽

Estrogen Receptor Α ◽

Papillary Thyroid ◽

Immunohistochemical Expression

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The Clinical Significance of Lymph Node Ratio and Ki-67 Expression in Papillary Thyroid Cancer

World Journal of Surgery ◽

10.1007/s00268-021-06070-y ◽

2021 ◽

Author(s):

Helene Lindfors ◽

Catharina Ihre Lundgren ◽

Jan Zedenius ◽

C. Christofer Juhlin ◽

Ivan Shabo

Keyword(s):

Thyroid Cancer ◽

Lymph Node ◽

Papillary Thyroid Cancer ◽

Tumor Recurrence ◽

Lymph Node Ratio ◽

Papillary Thyroid ◽

Ki 67 ◽

Node Ratio ◽

N Stage

Abstract Background The N stage in papillary thyroid cancer (PTC) is an important prognostic factor based on anatomical localization of cervical lymph nodes (LNs) only and not the extent of lymphatic metastasis. In this retrospective study, the clinical significance of lymph node ratio (LNR) and tumor cell proliferation in relation to the conventional classification of PTC was explored. Methods Patients diagnosed with PTC at the Karolinska University Hospital in Stockholm, Sweden, during the years 2009–2011 were included. The LNR, defined as the number of metastatic LNs divided by the total number of LNs investigated, and the Ki-67 index were analyzed in relation to clinical data. Results The median number of LN removed was 16 with the following N stage distribution: N0 (26%), N1a (45%), and N1b (29%). A Ki-67 index of ≥3% was significantly correlated with the presence of metastases and tumor recurrence with a sensitivity of 50% and specificity of 80% (p = 0.015). Lymph node ratio ≥21% was related to tumor recurrence with sensitivity of 89% and specificity of 70% (p = 0.006). Patients with LN metastases in the lateral cervical compartment only had significantly lower LNR (14.5%) compared to those with both central and lateral cervical metastases (39.5%) (p = 0.004) and exhibited no tumor recurrence. Increased Ki-67 index was significantly related to LNR ≥21% (p = 0.023) but was not associated with N stage. Conclusions The Ki-67 proliferation index and LNR may better reflect the malignant behavior of PTC compared to the anatomical classification of LN metastases solely.

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KI-67 INDEX AND TYPE OF HSP70 EXPRESSION IN THE FORMATION OF PROGNOSTIC GROUPS OF PATIENTS WITH PAPILLARY THYROID CANCER

Russian Journal of Oncology ◽

10.18821/1028-9984-2018-23-2-90-95 ◽

2018 ◽

Vol 23 (2) ◽

pp. 90-95

Author(s):

Anatoliy A. Ivanov ◽

A. M Avdalyan ◽

E. L Lushnikova ◽

O. P Molodykh ◽

Yu. N Zorkina ◽

...

Keyword(s):

Thyroid Cancer ◽

Survival Rate ◽

Papillary Thyroid Cancer ◽

Mixed Type ◽

Hsp70 Expression ◽

Papillary Thyroid ◽

Ki 67 ◽

Favorable Prognosis ◽

Prognosis Group ◽

Cytoplasmic Type

The aim of our work was to determine the possibility of stratification of papillary thyroid cancer (PTC) patients into prognosis groups depending on the Ki-67 index and the type of HSP70 expression. The study included 89 patients with a known prognosis for the period of 2005-2017, treated for PTC over the period of 2005-2013. The immunohistochemical study was carried out with Ki-67 and HSP70 antibodies on the Ventana XT Steiner device using standard protocols. The method of tissue matrices was used to standardize the study. Different variants of PTC, depending on the level of Ki-67 expression in combination with the HSP70 response allowed identifying 3 groups of PTC prognosis. The favorable prognosis group included patients with samples with cytoplasmic type of HSP70 expression and Ki-67 response < 6.3%, with mixed type of HSP70 expression and Ki-67 response < 6.3%, with cytoplasmic HSP70 expression and Ki-67 response > 6.3%. The intermediate prognosis group consisted of patients with tumors with mixed type of HSP70 expression and Ki-67 response > 6.3%, with nuclear HSP70 expression and Ki-67 response < 6.3%. The group of poor prognosis included patients with nuclear HSP70 expression and Ki-67 response > 6.3%. In the group of favorable prognosis, the 10-year survival rate was 89.6 ± 3.5%. In the intermediate prognosis group, the 10-year survival rate was 45 ± 14.5% and in the unfavorable prognosis group, no patient survives 6 years.

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Loss of Integrase Interactor 1 (INI1) Expression in a Subset of Differentiated Thyroid Cancer

Diagnostics ◽

10.3390/diagnostics10050280 ◽

2020 ◽

Vol 10 (5) ◽

pp. 280 ◽

Cited By ~ 1

Author(s):

Kung-Chen Ho ◽

Jie-Jen Lee ◽

Chi-Hsin Lin ◽

Ching-Hsiang Leung ◽

Shih-Ping Cheng

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

The Cancer Genome Atlas ◽

Papillary Thyroid ◽

Immunohistochemical Expression ◽

Follicular Variant ◽

Chromatin Remodeling Complex ◽

Cancer Genome Atlas ◽

Integrase Interactor 1 ◽

Benign Thyroid

Alterations in the switching defective/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complex are enriched in advanced thyroid cancer. Integrase interactor 1 (INI1), encoded by the SMARCB1 gene on the long arm of chromosome 22, is one of the core subunits of the SWI/SNF complex. INI1 immunohistochemistry is frequently used for the diagnosis of malignant rhabdoid neoplasms. In the present study, we found normal and benign thyroid tissues generally had diffusely intense nuclear immunostaining. Loss of INI1 immunohistochemical expression was observed in 8% of papillary thyroid cancer and 30% of follicular thyroid cancer. Furthermore, loss of INI1 expression was associated with extrathyroidal extension (p < 0.001) and lymph node metastasis (p = 0.038). Analysis of The Cancer Genome Atlas database revealed that SMARCB1 underexpression was associated with the follicular variant subtype and aneuploidy in papillary thyroid cancer. We speculate that SMARCB1 is an important effector in addition to NF2 and CHEK2 inactivation among thyroid cancers with chromosome 22q loss.

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THE BRAF MUTATION V600E IN PAPILLARY THYROID CANCER, CLINICAL-MORPHOLOGICALPARALLELES AND PROGNOSIS

Russian Journal of Oncology ◽

10.18821/1028-9984-2017-22-1-15-20 ◽

2017 ◽

Vol 22 (1) ◽

pp. 15-20

Author(s):

A. A Ivanov ◽

A. M Avdalyan ◽

V. J Gerval’d ◽

E. L Lushnikova ◽

Yu. N Zorkina ◽

...

Keyword(s):

Thyroid Cancer ◽

Lymph Nodes ◽

Papillary Thyroid Cancer ◽

Braf Mutation ◽

Negative Impact ◽

Morphological Characteristics ◽

Braf V600e ◽

Papillary Thyroid ◽

Ki 67 ◽

Regional Lymph Nodes

On the material of the 67 cases of papillary thyroid cancer (PTC) authors executed the study of the interrelationship between the BRAF mutation V600E and the forecast, biomolecular and morphological characteristics of the disease. There was implemented the analysis of samples for the presence of 7 KRAS gene mutations, 4 mutations of the PIK3CA gene, mutation BRAF V600E with the revealing of the interrelationship between such biomolecular markers for proliferation and apoptosis as Ki-67, p53, Bcl2. Also there was performed chromogenic hybridization (CISH method) in situ to study the status of the HER2 gene. There was determined the interrelationship between BRAF mutation V600E and clinical indices of prognosis: tumor sizes, capsule invasion, presence of metastases in regional lymph nodes. In addition, there was evaluated the interrelationship between BRAF mutation V600E and 10-years survival rate. No mutation were identified in KRAS, PI3K genes. BRAF mutation V600E was identified in 50 cases (75%). The frequency of V600E in women accounted of 75 ± 6.4%, in men - 67 ± 27.1%. In patients with the presence of V600E the size of a node was slightly less than in the absence of mutations and in 76% of cases did not reach the average value of 1.8 cm. Invasion into the capsule was identified in 35 ± 12.7% cases with a positive BRAF mutation V600E status and in 56 ± 8.4% - in cases with a negative status. Metastases in regional lymph nodes occurred in 36 ± 11.6% in patients with V600E and in 47 ± 18.9% of cases without this mutation. There was obtained the interrelationship between V600E and Ki-67: the average level of the proliferative activity in the presence of the given mutation was 4.4 ± 0.6%, in the absence - 9.4 ± 3.9%. No interrelationship was obtained between V600E and other biomolecular parameters or this interrelationship was tendentious in character. In terms of 10-years survival the groups with or without V600E statistically did not differ. Based on the data, it was possible to say about the absence of the negative impact of V600E on the prognosis in PTC patients

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Rosuvastatin induces apoptosis in cultured human papillary thyroid cancer cells

Journal of Endocrinology ◽

10.1530/joe-10-0411 ◽

2011 ◽

Vol 210 (1) ◽

pp. 105-115 ◽

Cited By ~ 25

Author(s):

N Dilara Zeybek ◽

Nese Ersoz Gulcelik ◽

F Figen Kaymaz ◽

Can Sarisozen ◽

Imran Vural ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Cancer Cells ◽

Papillary Thyroid Cancer ◽

Caspase 3 ◽

Thyroid Cell ◽

Papillary Thyroid ◽

Ki 67 ◽

Thyroid Cancer Cells

Statins show antiproliferative activity in various cancer cells. The aim of this study was to evaluate the effects of rosuvastatin treatment on papillary thyroid carcinoma. The papillary thyroid carcinoma (B-CPAP) and normal (Nthy-ori 3-1) thyroid cell lines were treated with rosuvastatin at 12.5, 18.5, 25, 50, 100, and 200 μM concentrations. After 48 and 72 h of rosuvastatin treatment, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, Ki-67 immunolabeling, FACS analysis, electron microscopy, caspase-3, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) analysis were performed. Decreased cell viability and G1 phase arrest were detected in papillary thyroid cell line treated with rosuvastatin. Positive immunoreactivity of Ki-67 and dose-dependent increase in S phase on Nthy-ori 3-1 cells were also detected. B-CPAP cells showed intense vacuolisation and autophagosomes with low concentrations and 48 h incubations, while Nthy-ori 3-1 cells showed these changes at higher concentrations. A decrease in the percentage of cells showing autophagy was determined with increasing concentrations of rosuvastatin in B-CPAP cells. Rosuvastatin treatment also caused a dose- and time-dependent increase in caspase-3 activity and apoptotic index by TUNEL assay in B-CPAP cells compared with the Nthy-ori 3-1 cells. Apoptotic cells with nuclear condensation and fragmentation were observed in B-CPAP cell line. Rosuvastatin induced autophagic changes in B-CPAP papillary thyroid cancer cells in lower doses and caused a shift from autophagy to apoptosis. Rosuvastatin may be an alternative treatment for refractory papillary thyroid cancer. Further in vivo studies are necessary to clarify the effects of rosuvastatin in papillary thyroid carcinoma and the clinical implications of rosuvastatin treatment.

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