scholarly journals RAS Mutations Are the Predominant Molecular Alteration in Poorly Differentiated Thyroid Carcinomas and Bear Prognostic Impact

2009 ◽  
Vol 23 (10) ◽  
pp. 1715-1715
Author(s):  
Marco Volante ◽  
Ida Rapa ◽  
Manoj Gandhi ◽  
Gianni Bussolati ◽  
Daniela Giachino ◽  
...  

ABSTRACT Context Poorly differentiated carcinomas represent an aggressive group of thyroid tumors with controversial classification placement and poorly understood pathogenesis. Molecular data in this group of tumors are extremely heterogeneous, possibly reflecting different inclusion criteria. Recently homogeneous diagnostic criteria have been proposed by our group (Turin proposal) that need to be complemented by detailed molecular characterization. Objective The objective of the study was to define a comprehensive molecular typing of poorly differentiated thyroid carcinomas classified following homogeneous diagnostic criteria. Design Sixty-five cases of poorly differentiated carcinoma selected following the Turin proposal have been screened for N-, K-, H-RAS, BRAF, RET/PTC1 and 3, and PAX8/PPARγ mutations-rearrangements using alternative techniques and in two different laboratories. Molecular data were compared with clinical pathological parameters and survival by univariate and multivariate analysis. Results RAS mutations in codon 61 were by far the most common genetic alteration in poorly differentiated carcinomas (23% of cases), with all mutation in NRAS except one in the HRAS gene. A single BRAF mutation was found in a poorly differentiated carcinoma with a residual component of a tall cell variant of papillary carcinoma. No KRAS, RET/PTC, or PAX8/PPARγ genetic alteration was detected. In this series, the presence of RAS mutations was a unique negative prognostic parameter at multivariate analysis. Conclusions The present study demonstrates that strictly classified poorly differentiated carcinomas are genetically homogeneous, RAS mutations being the almost exclusive genetic event. Moreover, the detection of RAS mutations might be clinically relevant for the prognostic stratification of these tumors.

2009 ◽  
Vol 94 (12) ◽  
pp. 4735-4741 ◽  
Author(s):  
Marco Volante ◽  
Ida Rapa ◽  
Manoj Gandhi ◽  
Gianni Bussolati ◽  
Daniela Giachino ◽  
...  

2009 ◽  
Vol 30 (6) ◽  
pp. 747-747
Author(s):  
Marco Volante ◽  
Ida Rapa ◽  
Manoj Gandhi ◽  
Gianni Bussolati ◽  
Daniela Giachino ◽  
...  

2009 ◽  
Vol 133 (5) ◽  
pp. 683-691
Author(s):  
Ronald Ghossein

Abstract Context.—Despite past and recent efforts, many problems and controversies remain in the classification of thyroid carcinomas of follicular cell origin. These controversies have an impact on the prognosis and therapy of patients with thyroid carcinoma as well as on the development of robust cutting-edge research aimed at better outcome and quality of life. Objective.—To focus on 3 contentious areas with significant clinical value: the follicular variant of papillary thyroid carcinoma, the extent of invasion in follicular carcinoma, and the poorly differentiated thyroid carcinomas. Data Sources.—The published English language literature was reviewed. Conclusions.—Recent data show that prognosis and therapy for many disease entities can be better delineated if a meticulous microscopic examination is performed. An accurate assessment of the extent of invasion (especially vascular) is crucial. Proliferative grading (ie, mitosis and necrosis) is of high prognostic value and should be looked for in every specimen. In addition, molecular data gathered to date can help reassess these tumors at the histologic level. Classification proposals based on personal experience rather than adequate and careful clinical follow-up should be discouraged.


2021 ◽  
Vol 15 (1) ◽  
pp. 77-81
Author(s):  
Mahwish Niaz ◽  

Background: Thyroid cancer is the leading cause of death both in developing and developed countries. Patients present with enlarged thyroid. Radiology shows hot and cold nodules. Thyroidectomy or lobectomy is done to rule out malignancy. Objective: To determine the incidence of thyroid carcinomas and other pathologies in thyroidectomy specimen of different age group patients presenting with clinically enlarged thyroid. Study Design: Cross-sectional study. Settings: Department of Histopathology, Foundation University Medical College (FUMC), Islamabad and Department of surgery, Fauji Foundation Hospital (FFH), Rawalpindi Pakistan. Duration: from Jan 2012 to March 2019. Methodology: All the thyroidectomies specimens send from Surgery department of FFH to Histopathology Department of FUMC during study period and fulfilling the pre-set criteria were included in the study. All the data and results were analyzed using SPSS version 17.0. Results: Out of 500 total patients, 89% (n=445) were diagnosed as having multinodular goiter, 2.6% (n=13) thyroiditis, 2.2% (n=11) follicular adenoma, 0.8% (n=4) Hurthle cell adenoma, 0.2%(n=1) hyalinizing trabacular adenoma and thyroid carcinomas. The carcinomas comprised 2.6%(n=13) papillary carcinoma, 0.8%(n=4) poorly differentiated carcinoma,0.8%(n=4) anaplastic carcinoma,0.6%(n=3) medullary carcinoma and 0.4%(n=2) follicular carcinoma. In 445 patients of multinodular goiter 158 patients were in the age range of 41-50 years, in 13 cases of thyroiditis 7 were in the age range of 31-40 years, in 11 cases of follicular adenoma 4 patients were in the age range of 31-40 years, in 4 cases of hurthle cell adenoma 3 patients were in the age range of 41-50 years, in 13 cases of papillary thyroid carcinoma 5 patients were in the age range of 31-40 years, in 4 cases of poorly differentiated carcinoma 2 patients were in the age range of 41-50 years and in 4 cases of anaplastic carcinoma 2 patients were in the age range of 61-70 years. Conclusion: The study concluded that thyroid carcinomas collectively constituted 5.20% of the study cases. Papillary carcinoma was the most frequent malignant neoplasm constituting 2.6 % and occurring mostly in the age range of 31-40 years, while anaplastic carcinoma comprised of 0.8% of malignant lesions occurring in the age range of 61-70 years. The most frequent cause of thyroid enlargement was multinodular goiter (89%) with majority of the patients in the age range of 41-50 years.


2021 ◽  
pp. 106689692110195
Author(s):  
Grosse Claudia ◽  
Grosse Alexandra

Nuclear protein in testis (NUT) carcinoma represents a highly aggressive, poorly differentiated carcinoma that is genetically defined by rearrangement of NUT gene. The histomorphological appearance ranges from entirely undifferentiated carcinoma to carcinoma with prominent squamous differentiation. NUT carcinoma can display neuroendocrine features. Although it is typically distributed along the midline axis, it may manifest in nonmidline locations. The majority of patients develop rapidly disseminated disease. We illustrate 2 cases of NUT carcinoma, one located in the lung, which closely resembled a neuroendocrine carcinoma, and the other one with assumed lung origin demonstrating metastatic dissemination with diffuse bone involvement, which was clinically first suspected to be a hematological malignancy. Due to its undifferentiated nature, NUT carcinoma may be confused with many entities. NUT immunohistochemistry is considered to be sufficient for the diagnosis. Fluorescence in-situ hybridization analysis and next-generation sequencing are currently used to confirm the diagnosis.


2006 ◽  
Vol 13 (1) ◽  
pp. 257-269 ◽  
Author(s):  
G Riesco-Eizaguirre ◽  
P Gutiérrez-Martínez ◽  
M A García-Cabezas ◽  
M Nistal ◽  
P Santisteban

The oncogene BRAFV600E is the most frequent genetic event in papillary thyroid carcinoma (PTC) but its prognostic impact still remains to be elucidated. We evaluated a representative series of 67 individuals with PTC who underwent total thyroidectomy. BRAF-positive tumours correlated with early recurrences (32% vs 7.6%; P=0.02) during a median postoperative follow-up period of 3 years. Interestingly, within the recurrences, a significant majority had negative radioiodine (131I) total body scans, predicting a poorer outcome as treatment with 131I is not effective. This last observation led us to investigate the role of BRAFV600E and the MEK-ERK pathway in thyroid dedifferentiation, particularly in Na+/I− symporter (NIS) impairment, as this thyroid-specific plasma membrane glycoprotein mediates active transport of I− into the thyroid follicular cells. A subset of 60 PTC samples was evaluated for NIS immunoreactivity and, accordingly, we confirmed a significant low NIS expression and impaired targeting to membranes in BRAF-positive samples (3.5% vs 30%; P=0.005). Furthermore, experiments with differentiated PCCl3 thyroid cells demonstrated that transient expression of BRAFV600E sharply impaired both NIS expression and targeting to membrane and, surprisingly, this impairment was not totally dependent on the MEK-ERK pathway. We have concluded that BRAFV600E is a new prognostic factor in PTC that correlates with a high risk of recurrences and less differentiated tumours due to the loss of NIS-mediated 131I uptake.


2004 ◽  
Vol 89 (5) ◽  
pp. 2414-2420 ◽  
Author(s):  
Efisio Puxeddu ◽  
Sonia Moretti ◽  
Rossella Elisei ◽  
Cristina Romei ◽  
Raffaela Pascucci ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Agnieszka Halon ◽  
Piotr Donizy ◽  
Przemyslaw Biecek ◽  
Julia Rudno-Rudzinska ◽  
Wojciech Kielan ◽  
...  

The role of HER-2 expression as a prognostic factor in gastric cancer (GC) is still controversial. The aim of the study was to asses HER-2 status, its correlations with clinicopathological parameters, and prognostic impact in GC patients. Tumor samples were collected from 78 patients who had undergone curative surgery. In order to evaluate the intensity of immunohistochemical (IHC) reactions two scales were applied: the immunoreactive score according to Remmele modified by the authors and standardised Hercep test score modified for GC by Hofmann et al. The HER-2 overexpression was detected by IHC in 23 (29.5%) tumors in Hercep test (score 2+/3+) and in 24 (30.7%) in IRS scale (IRS 4–12). The overexpression of HER-2 was associated with poorly differentiated tumors, but this correlation was not significant (P=0.064). No relationship was found between HER-2 expression and primary tumor size and degree of spread to regional lymph nodes. Both univariate and multivariate analyses revealed that TNM stage and patient’s age were the crucial negative prognostic factors. No correlation was observed between patient survival and expression of HER-2 estimated using both scales. This research did not confirm HER-2 expression (evaluated with immunohistochemistry) value as a prognostic tool in GC.


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