Purpose Clear cell renal cell cancers frequently harbor Von Hippel-Lindau gene mutations, leading to stabilization of the hypoxia-inducible factors (HIFs) and their target genes. In this study, we investigated the relationship between vascular endothelial growth factor (VEGF), HIF-1α, HIF-2α, p53 positivity, microvessel density, and Ki-67 rates with prognostic histopathologic factors (Fuhrman nuclear grade, stage, and sarcomatoid differentiation) and survival in clear cell renal cell carcinomas.Material and Methods Seventy-two nephrectomy specimens diagnosed as clear cell renal cell carcinoma between 2000 and 2012 were reevaluated. Immunohistochemically VEGF, HIF-1α, HIF-2α, p53, CD34 (for microvessel density evaluation), and Ki-67 antibodies were applied to the tumor areas. The relationships of these antibodies with prognostic factors and survival rates were evaluated with statistical analyses.Results Mean survival time was 105.6 months in patients with ccRCC. Patients with high expression of VEGF, HIF-1α and HIF-2α positivity, a high Ki-67 proliferation index, and a high microvessel density evaluation score had a shorter survival time (p<0.05).Conclusions Our findings supported that with the use of these immunohistochemical markers, prognosis of renal cell carcinoma may be predicted at the first step of patient management. New treatment modalities targeted to HIF-1α and HIF-2α might be planned as well as VEGF-targeted therapies in the management of clear cell renal cell carcinomas.
Background:Gastrointestinal stromal tumors (GIST) have KIT or platelet-derived growth factor receptor α (PDGFRα) mutations affecting receptor tyrosine kinase activity and do not benefit from classic treatment regimens. Aims: The aim of this study was to review the algorithm that may be followed for the diagnosis and differential diagnosis in GISTs by investigating the histomorphological parameters and expression characteristics of classical immunohistochemical antibodies used in routine tests in addition to DOG1 expression. Study Design: Diagnostic accuracy study. Methods: We reevaluated the histological and immunohistochemical parameters of 37 GISTs. The standard immunohistochemical diagnosis and differential diagnosis panel antibodies (CD117, PDGFRα, CD34, vimentin, desmin, SMA, S-100, and Ki67) were studied on the tumor sections. We also used the popular marker DOG1 antibody with accepted sensitivity for GISTs in recent years and the PDGFRα immune marker for which the benefit in routine practice is discussed. Results: Classification according to progressive disease risk groups of the 37 cases revealed that 54% were in the high risk, 19% in the moderate risk, 16% in the low risk, 8% in the very low risk and 8% in the no risk group. Cytological atypia, necrosis, mucosal invasion and the Ki67 index were found to be related to the progressive disease risk groups of the tumors (p<0.05). Positive immunoreaction was observed with CD117 and PDGFRα in all GISTs in the study (100%). Positivity with the DOG1 antibody was found in 33 (89%) cases. CD34 was positive in 62% (23) of the cases. Conclusion: The CD117 antibody still plays a key role in GIST diagnosis. However, the use of DOG1 and PDGFRα antibodies combined with CD117 as sensitive markers can be beneficial.
Lymphovascular invasion (LVI) is an important prognostic factor in various solid tumors, however, data on the association between LVI and thyroid carcinomas are limited. In this study, we evaluated the relationship between LVI and clinicopathological features of papillary thyroid carcinoma (PTC). Six hundred seventy-eight patients diagnosed with PTC between 2012 and 2015 were included into the study. Patients were classified based on the presence or absence of LVI. Gender, age, ultrasonography (US), tumor size and multifocality, BRAFV600E mutation, perineural and capsular invasion, extrathyroid extension (ETE), nodal metastasis, and recurrences were evaluated, and risk analysis was performed for each parameter. The number of patients with LVI [LVI (+)] was 63, while the number of patients without LVI [LVI (-)] was 615. The female/male ratio was 564/114. LVI was present in 18.4% of male patients and in 7.4 % of female patients. In the age group between 17-25 years LVI was detected in 6/13 patients, and this result was statistically significant compared to other age groups (p = 0.004). Suspicious lymph nodes upon US, perineural or capsular invasion, ETE, tumor size, and nodal metastasis were significantly more frequent in LVI (+) group (p < 0.001). The frequency of BRAFV600E mutation was also significantly higher in LVI (+) group (p < 0.001). Overall, the presence of LVI was associated with gender, tumor size, age, lymph node metastasis, pathological lymph nodes, perineural and capsular invasion, ETE, and BRAFV600E mutation. These results suggest that in PTC patients undergoing thyroidectomy, the presence of LVI should be considered as an indicator of aggressive clinicopathological features and those patients should be followed up carefully for recurrences and metastasis.
Prophylactic lymph node dissection is still controversial due to the potentially surgery-related morbidity in management of papillary thyroid carcinomas. So, some histopathological predictors for lymph node metastasis in thyroidectomy specimens may reveal importance. The objective of this study was to define histomorphological indicators of lymph node metastasis in the patients who had been performed thyroidectomy without lymph node dissection. Clinicopathological features of patients archived in Department of Pathology at Trakya University Medical Faculty were reviewed. A total of 211 patients who had been diagnosed as papillary carcinoma and had been performed total thyroidectomy/lobectomy with central/cervical lymph node dissection were included in the study. Clinical features (age, gender, preoperative/postoperative clinical, and laboratory findings) and histopathological features (histological variant, tumor size, focality, extrathyroidal extension, tumor border, lateral tubular growth, intraglandular dissemination, stromal and lymphocytic tumor response, lymphocytic thyroiditis, lymphovascular invasion, lymph node metastasis, number of metastatic lymph nodes, extranodal extension, size of the metastatic foci) were evaluated. Male gender, conventional variant, tumor size greater than 10 mm, multifocality, extrathyroidal extension, lateral tubular growth, intraglandular dissemination, lymphocytic and stromal tumor response, and absence of lymphocytic thyroiditis were predictive, and older age (≥45 years) and follicular variant PTC were protective for lymph node metastasis. In order to optimize the management of papillary thyroid carcinomas, pathologists should search for the clues of lymph node metastasis particularly intraglandular dissemination, lateral tubular growth, tumor border and lymphocytic/stromal tumor response, multifocality, concomitant lymphocytic thyroiditis besides the actual prognostic criteria especially in younger aged male patients.
Incidental papillary thyroid carcinomas (IPTCs) consist of a significant portion of increasing incidence in papillary thyroid carcinomas. This study investigated the clinicopathological features of IPTCs from different perspectives and by comparing nonincidental PTCs (NIPTCs) in patients who underwent total thyroidectomy and lymph node dissection. Basic results were as follows. IPTC was present in 27.9% of 308 patients. IPTCs were significantly accompanied by lymphocytic thyroiditis (LT), particularly, multinodular hyperplasia (MNH). IPTCs were more common in older patients (51.3 years vs. 47.2 years) and in female patients. IPTCs significantly differed from NIPTCs in terms of smaller tumour size, lymphatic vessel invasion (2.6% vs. 97.4%), extrathyroidal extension (4.3% vs. 95.7%), lymph node metastasis (3.6% vs. 96.4%), multifocality (21.2% vs. 78.8%), bilaterality (5.3% vs. 94.7%), and BRAFV600 mutation (6.7% vs. 93.3%). Older age, bilaterality, encapsulation, and radioactive iodine (RAI) were significantly more common in IPTCs > 5 mm than in those ≤ 5 mm. In conclusion, IPTCs are more commonly associated with LT and MNH. IPTCs may have a more favourable prognosis than NIPTCs, and tumour size > 5 mm may predict bilaterality and need for RAI. Nevertheless, the patient-based clinical approach in IPTCs may have benefits in the management of IPTCs.
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