Publications by authors named "Maria Rosa Bella Cueto"

6 Publications

  • Page 1 of 1

Genetic Determinants for Prediction of Outcome of Patients with Papillary Thyroid Carcinoma.

Cancers (Basel) 2021 Apr 23;13(9). Epub 2021 Apr 23.

IPATIMUP-Instituto de Patologia e Imunologia Molecular da Universidade do Porto, 4200-135 Porto, Portugal.

Papillary thyroid carcinoma (PTC) usually presents an excellent prognosis, but some patients present with aggressive metastatic disease. BRAF, RAS, and TERT promoter (TERTp) genes are altered in PTC, and their impact on patient outcomes remains controversial. We aimed to determine the role of genetic alterations in PTC patient outcomes (recurrent/persistent disease, structural disease, and disease-specific mortality (DSM)). The series included 241 PTC patients submitted to surgery, between 2002-2015, in a single hospital. DNA was extracted from tissue samples of 287 lesions (primary tumors and metastases). Molecular alterations were detected by Sanger sequencing. Primary tumors presented 143 BRAF, 16 TERTp, and 13 RAS mutations. Isolated TERTp showed increased risk of structural disease (HR = 7.0, < 0.001) and DSM (HR = 10.1, = 0.001). Combined genotypes, BRAF/TERTp (HR = 6.8, = 0.003), BRAF/TERTp (HR = 3.2, = 0.056) and BRAF/TERTp (HR = 2.2, = 0.023) showed increased risk of recurrent/persistent disease. Patients with tumors BRAF/TERTp (HR = 24.2, < 0.001) and BRAF/TERTp (HR = 11.5, = 0.002) showed increased risk of structural disease. DSM was significantly increased in patients with TERTp regardless of BRAF status (BRAF/TERTp, log-rank < 0.001; BRAF/TERTp, log-rank < 0.001). Our results indicate that molecular markers may have a role in predicting PTC patients' outcome. BRAF/TERTp tumors were prone to associate with local aggressiveness (recurrent/persistent disease), whereas TERTp tumors were predisposed to recurrent structural disease and DSM.
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April 2021

Clinicopathological Features as Prognostic Predictors of Poor Outcome in Papillary Thyroid Carcinoma.

Cancers (Basel) 2020 Oct 29;12(11). Epub 2020 Oct 29.

IPATIMUP-Instituto de Patologia e Imunologia Molecular, Universidade do Porto, 4200-135 Porto, Portugal.

Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients' outcomes and find which indicators are more adequate for tailoring surgical procedures and follow-up. We studied a series of 241 PTC patients submitted to surgery. All patients' files and histological tumor samples were reviewed. The 8th edition AJCC/UICC (American Joint Committee on Cancer/Union for International Cancer) Controlstaging system and the 2015 American Thyroid Association risk stratification system were used. Total thyroidectomy was performed in 228 patients, lymphadenectomy in 28 patients. Gross extrathyroidal extension (ETE) was present in 10 patients and 31 tumor resection margins were incomplete. Cervical lymph node metastases (LNMs) were present in 34 patients and distant metastases at diagnosis in four patients. In multivariate analysis, male gender (OR = 15.4, = 0.015), venous invasion (OR = 16.7, = 0.022), and lateral compartment LNM (OR = 26.7, = 0.004) were predictors of mortality; psammoma bodies (PBs) (OR = 4.5, = 0.008), lymph vessel invasion (OR = 6.9, < 0.001), and gross ETE (OR = 16.1, = 0.001) were predictors of structural disease status; male gender (OR = 2.9, = 0.011), lymph vessel invasion (OR = 2.8, = 0.006), and incomplete resection margins (OR = 4.6, < 0.001) were predictors of recurrent/persistent disease. Our study supports that the factors helping to tailor patient's surgery are male gender, presence of PBs, gross ETE, and lateral compartment LNM. Together with pathological factors, lymph vessel invasion, venous invasion, necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of patients.
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October 2020

[Tumors of the thyroid gland. Proposal for the management and study of samples from patients with thyroid neoplasms].

Rev Esp Patol 2020 Jan - Mar;53(1):27-36. Epub 2019 May 7.

IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal; Department of Pathology, Hospital de S. João, Porto, Portugal.

The recent changes in the classification and staging of thyroid tumors have arisen from the need to provide an adequate response to the exponential increase of thyroid cancer, which, however, has not been accompanied by an increase in mortality. These changes pretend to reduce overdiagnoses of malignancy, unnecessary treatment, side effects as well as cost for the health system. To this end, this article reviews recommendations for the management of thyroid surgical pathology samples with emphasis on the new terminology of the WHO classification. The basic criteria for the diagnosis of malignancy in well-differentiated thyroid carcinomas are reviewed and the criteria for NIFTP (non-invasive follicular tumor with papillary-like nuclear features) diagnosis are updated. Recommendations for the elaboration of the pathological report are also included.
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March 2021

Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome.

J Gastrointest Oncol 2017 Oct;8(5):E73-E79

Department of Hepatobiliopancreatic Surgery, Parc Taulí, Hospital Universitari, Sabadell, Barcelona, Spain.

Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and sebomatricoma. With the exception of one P-NET, all these conditions were associated with LS, as confirmed by immunohistochemistry (IHC) and polymerase chain reaction (PCR). LS is caused by a mutation of a mismatch repair (MMR) gene which leads to a loss of expression of its protein. CRC is the most common tumor, followed by EC. Pancreatic tumors have also been associated with LS. Diagnosis of LS is based on clinical criteria (Amsterdam II and Bethesda) and genetic study (MMR gene mutation). The association between LS and our patient's tumors was confirmed by IHC (loss of expression of proteins MLH1 and its dimer PMS2) and the detection of microsatellite instability (MSI) using PCR.
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October 2017

Ectopic thyroid tissue in the adrenal gland: a report of two cases with pathogenetic implications.

Thyroid 2013 Dec 25;23(12):1644-50. Epub 2013 Jul 25.

1 National Cancer Institute , Bogota, Colombia .

Background: Ectopic thyroid tissue is usually found anywhere along the embryonic descent pathway of the medial thyroid anlage from the tongue to the trachea (Wölfler area). However, ectopic thyroid tissue in the adrenal gland (ETTAG) is not easy to understand on the basis of thyroid embryology; because it is so rare, the possibility of metastasis should first be considered. Here, we describe two cases of ETTAG with pathogenetic implications and review the associated literature.

Patient Findings: Two cases of ETTAG presented as incidental cystic adrenal masses in adult females, one having a congenital hernia of Morgagni. The ETTAG was histologically indistinguishable from normal orthotopic thyroid tissue, and its follicular nature was confirmed by immunohistochemical positivity for thyroglobulin, thyroperoxidase, thyroid transcription factor-1 (TTF-1/Titf-1/Nkx2.1), cytokeratin AE1/AE3, cytokeratin 7, pendrin, human sodium iodide symporter, paired box gene 8, and forkhead box E1 (TTF-2), as well as positivity for the messenger RNA of the thyroglobulin gene by in situ hybridization analysis. No C cells (negativity for calcitonin, chromogranin, and synaptophysin) were present. Neither BRAF nor KRAS mutations were detected with real-time polymerase chain reaction analysis. Further work-up did not show evidence of thyroid malignancy.

Summary: ETTAG is a rare finding, with only seven cases reported; women are much more frequently affected than men (8:1), and it usually presents in the fifth decade (mean age 54, range 38-67) as a cystic adrenal mass incidentally discovered on abdominal ultrasonography and/or in computed tomography images. ETTAG is composed of normal follicular cells without C cells. The expression of some transcription factors (TTF-1, paired box gene 8, and FOXE1) involved in development and/or migration of the medial thyroid anlage is preserved. Coexistence of a congenital hernia of Morgagni in one patient suggests an overdescent of medial thyroid anlage-derived cells in its pathogenesis.

Conclusion: Although ETTAG pathogenesis remains unknown, the lack of C cells together with the coexistence of a congenital defect of the anterior diaphragm (hernia of Morgagni) in one of our patients could suggest an overdescent of medial thyroid anlage-derived cells in the origin of this heterotopia.
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December 2013

Real-time PCR improves Helicobacter pylori detection in patients with peptic ulcer bleeding.

PLoS One 2011 20;6(5):e20009. Epub 2011 May 20.

Digestive Diseases Department, Hospital de Sabadell, Institut Universitari Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Spain.

Background And Aims: Histological and rapid urease tests to detect H. pylori in biopsy specimens obtained during peptic ulcer bleeding episodes (PUB) often produce false-negative results. We aimed to examine whether immunohistochemistry and real-time PCR can improve the sensitivity of these biopsies.

Patients And Methods: We selected 52 histology-negative formalin-fixed paraffin-embedded biopsy specimens obtained during PUB episodes. Additional tests showed 10 were true negatives and 42 were false negatives. We also selected 17 histology-positive biopsy specimens obtained during PUB to use as controls. We performed immunohistochemistry staining and real-time PCR for 16S rRNA, ureA, and 23S rRNA for H. pylori genes on all specimens.

Results: All controls were positive for H. pylori on all PCR assays and immunohistochemical staining. Regarding the 52 initially negative biopsies, all PCR tests were significantly more sensitive than immunohistochemical staining (p<0.01). Sensitivity and specificity were 55% and 80% for 16S rRNA PCR, 43% and 90% for ureA PCR, 41% and 80% for 23S rRNA PCR, and 7% and 100% for immunohistochemical staining, respectively. Combined analysis of PCR assays for two genes were significantly more sensitive than ureA or 23S rRNA PCR tests alone (p<0.05) and marginally better than 16S rRNA PCR alone. The best combination was 16S rRNA+ureA, with a sensitivity of 64% and a specificity of 80%.

Conclusions: Real-time PCR improves the detection of H. pylori infection in histology-negative formalin-fixed paraffin-embedded biopsy samples obtained during PUB episodes. The low reported prevalence of H. pylori in PUB may be due to the failure of conventional tests to detect infection.
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October 2011