Search

Background: Breast cancer (BC) is a significant burden on healthcare systems, especially in low- and middle-income countries where access to diagnosis and treatment is challenging. Objectives: The purpose of this study was to assess the diagnostic accuracy and cost using tissue microarray (TMA) instead of traditional immunohistochemical (IHC) evaluation for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and the proliferation marker Ki-67 and BC subtyping within the Brazilian public health system. Design: This is a retrospective cohort study comparing TMA slides with traditional whole-slide evaluation for IHC markers in 242 BC cases. Methods: We used formalin-fixed tissue blocks for TMA assembly. Clinical data and IHC scores for ER, PR, HER2, and Ki-67 were obtained from pathology reports. Cohen's kappa (k) was used to assess TMA performance. Results: BC samples were distributed in 10 TMAs and 968 cores were scored (242 BC cases × 4 markers). In 97% of these, TMA reached high quality to adequate IHC scoring with minimal technical issues. Inter-examiner agreement was almost perfect for all markers (ranging from 0.85 for HER2 to 0.91 for ER, p < 0.001). The intratumoral heterogeneity ranged from almost perfect agreement for ER and HER2 to moderate to substantial for PR and Ki-67. TMA offers substantial time and cost savings, with an approximately 11-fold reduction compared to traditional methods. The concordance between TMA and original reports was almost perfect, with 93% overall agreement (k = 0.81, p < 0.001). However, TMA performance varied between markers, with intratumoral heterogeneity significantly impacting discordant results, particularly for Ki-67 and HER2. This ultimately affected the accuracy of BC subtyping. TMA performed well in identifying luminal A and triple-negative cases, but misclassification was common for luminal B and HER2-positive cases. Conclusion: TMA offers accurate and lower-cost results in the individualized IHC assessment of BC markers. However, we do not recommend the use of TMA in the subtyping of BC, where analysis of the whole section remains necessary for more accurate results. We advocate more studies using the TMA approach in the Brazilian public health system to advance women's health care. [ABSTRACT FROM AUTHOR]

Background: Despite the increasing recognition of PD-L1 as predictor of immunotherapeutic response in various malignancies, its role and prognostic significance in thyroid cancer remain underexplored and subject to debate. This study begins to address this gap by comprehensively analyzing PD-L1 expression in papillary thyroid carcinoma (PTC) and investigating its correlation with key clinicopathological variables. Methods: We conducted immunohistochemistry (IHC) to assess PD-L1 expression in whole-tissue sections from 121 primary papillary thyroid carcinoma (PTC) cases. We then analyzed the correlations between PD-L1 expression and various clinicopathological variables. Results: PD-L1 expression was detected in 33.1% of papillary thyroid carcinomas (PTCs), predominantly exhibiting weak to moderate intensity. Notably, this study found no significant correlation between PD-L1 expression and various clinicopathological variables. The lack of association with traditional factors such as age, sex, histological subtype, and tumor size suggests the complex and multifaceted nature of PD-L1 regulation in PTC. Multivariate logistic regression analysis identified chronic lymphocytic thyroiditis with oncocytic metaplasia as the sole independent predictor of PD-L1 expression (P = 0.014), underlining the potential influence of the tumor microenvironment on immune checkpoint expression in PTC. Conclusions: Our study underscores the intricate interplay between chronic lymphocytic thyroiditis with oncocytic metaplasia and PD-L1 expression in papillary thyroid carcinoma. The observed link suggests a potential avenue for therapeutic intervention using anti-PD-1/PD-L1 therapies in surgery-refractory PTC. Understanding the dynamics of immune checkpoint regulation in the context of the tumor microenvironment is crucial for devising effective treatment strategies. Future research endeavors should delve deeper into the molecular mechanisms underlying this interaction and explore its implications for patient outcomes. As the field of immunotherapy continues to evolve, our findings contribute valuable insights into the complex immunological landscape of thyroid cancer. [ABSTRACT FROM AUTHOR]

Background: The most frequent site of recurrence of differentiated thyroid cancer (DTC) is cervical lymph nodes (LNs), which often necessitates repeated surgical interventions and morbidity in a generally indolent disease. Data on active surveillance (AS) of small cervical nodal metastasis are still scarce, particularly in real-world clinical settings. In this study, we evaluated the DTC outcomes of AS of metastatic cervical LNs and explored factors associated with disease progression. Methods: We conducted a retrospective cohort study, including DTC patients with biopsy-proven metastatic cervical LNs, who were followed on AS in a tertiary care, university-based institution in Brazil. The inclusion criteria were cervical metastasis ≤2.0 cm and an AS duration of at least 6 months. We excluded lesions with aggressive histology, those in close proximity to or invading local structures. The primary outcome was disease progression (enlargement ≥3 mm in any diameter or a new cervical metastasis). Results: Data from 40 patients were analyzed. Most were female (77.5%) and had papillary thyroid cancer (97.5%). The mean age was 47.0 (± standard deviation 15.8) years. The 8th edition of the tumor, node, metastasis stage (TNM8) staging for DTC was as follows: 29 in stage I (74.4%), 8 in stage II (20.5%), and 2 in stage IV (5.0%). The median maximum LN diameter was 0.9 (interquartile range [IQR], 0.8–1.3) cm, and the median AS follow-up duration was 27.5 (IQR, 16.5–47.3) months. Disease progression occurred in 14 (35%) patients: 7 (17.5%) due to enlargement ≥3 mm, and 7 (17.5%) had new cervical metastasis. The cervical progression-free survival was 51.0 (confidence interval, 47.0–55.0) months. No demographic, oncological, or biochemical factors were associated with disease progression. Of the 14 patients with disease progression, 8 were referred for surgery. No permanent surgical complications were reported. Of the six patients who remained on AS despite disease progression, five showed no further progression during subsequent follow-up (range 6–40 months). Conclusions: We observed that most small metastatic cervical LNs remained stable and were safely managed with AS. Nevertheless, these observations are limited by the retrospective design, small sample size, and short follow-up. Further prospective and long-term studies are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Mutations in the ESR1 gene (ESR1 m) are important mechanisms of resistance to endocrine therapy in estrogen receptor–positive (ER+) metastatic breast cancer and have been studied as a potential therapeutic target, as well as a predictive and prognostic biomarker. Nonetheless, the role of ESR1 m as a possible mechanism of primary endocrine resistance, as well as whether it also occurs in tumors that are resistant to ET administered in early-stage disease as (neo)adjuvant, has not been adequately studied. In this study, we evaluated the prevalence of ESR1 m in tumor samples from patients with ER+ breast cancer resistant to neoadjuvant aromatase inhibitor therapy. Methods: We followed a prospective cohort of patients with ER+ HER2– stages II and III breast cancer treated with neoadjuvant endocrine therapy (NET). Tumor samples from patients with a pattern of primary endocrine resistance [defined as a Preoperative Endocrine Prognostic Index (PEPI) score of ≥4] were identified and analyzed for the presence of ESR1 m. Results: One hundred twenty-seven patients were included in the cohort, of which 100 (79%) had completed NET and underwent surgery. Among these patients, the PEPI score ranged from 0 to 3 in 70% (70/100), whereas 30% (30/100) had a PEPI score of 4 or more. Twenty-three of these patients were included in the analysis. ESR1 mutations were not identified in any of the 23 patients with early-stage ER+ breast cancer resistant to NET. Discussion: Growing evidence supports the notion that there are different mechanisms for primary and secondary endocrine resistance. Our study suggests that ESR1 mutations do not evolve rapidly and do not represent a common mechanism of primary endocrine resistance in the neoadjuvant setting. Therefore, ESR1 m should be considered a mechanism of acquired endocrine resistance in the context of advanced disease. Further research should be conducted to identify factors associated with intrinsic resistance to ET. [ABSTRACT FROM AUTHOR]

Background: The role of serum TSH concentrations as a predictor of malignancy of thyroid nodule remains unclear. Objective: To prospectively evaluate the usefulness of serum TSH levels as a predictor of malignancy in thyroid nodules. Methods: Patients with thyroid nodule(s) who underwent fine-needle aspiration biopsy under ultrasonographic guidance in a tertiary, university-based hospital were consecutively evaluated. Patients with known thyroid cancer and/or patients receiving thyroid medication were excluded. Serum TSH levels were measured by two differents methodologies, chemiluminescent (CLIA) and electrochemiluminscent immunoassay (ECLIA). Anatomopathological exam of tissue samples obtained at thyroidectomy was considered the gold standard for the diagnosis of thyroid cancer. Results: A total of 615 patients participated in the study. The mean age was 55.9±14.7 years, and 544(88.5%) were female. The median TSH values were 1.48 and 1.55 μU/mL, using CLIA and ECLIA, respectively. One-hundred-sixty patients underwent thyroidectomy and the final diagnoses were malignant in 47(29.4%) patients. TSH levels were higher in patients with malignant than in those with benign nodules in both TSH assays: 2.25 vs. 1.50; P = 0.04 (CLIA) and 2.33 vs. 1.27; P = 0.03 (ECLIA). Further analysis using binary logistic regression identified elevated TSH levels, a family history of thyroid cancer, the presence of microcalcifications, and solitary nodule on US as independent risk factors for malignancy in patients with thyroid nodules. Additional analyses using TSH levels as a categorical variable, defined by ROC curve analysis, showed that the risk of malignancy was approximately 3-fold higher in patients with TSH levels ≥2.26 μU/mL than in patients with lower TSH levels (P = 0.00). Conclusions: Higher serum TSH levels are associated with an increased risk of thyroid cancer in patients with thyroid nodules. Using TSH levels as an adjunctive diagnostic test for stratifying the risk of malignancy associated with a thyroid nodule may help on defining the best therapeutic approaches. [ABSTRACT FROM AUTHOR]

Thyroid hormones (THs) are critical regulators of cellular processes, while changes in their levels impact all the hallmarks of cancer. Disturbed expression of type 3 deiodinase (DIO3), the main TH-inactivating enzyme, occurs in several human neoplasms and has been associated with adverse outcomes. Here, we investigated the patterns of DIO3 expression and its prognostic significance in breast cancer. DIO3 expression was evaluated by immunohistochemistry in a primary cohort of patients with breast cancer and validated in a second cohort using RNA sequencing data from the TCGA database. DNA methylation data were obtained from the same database. DIO3 expression was present in normal and tumoral breast tissue. Low levels of DIO3 expression were associated with increased mortality in the primary cohort. Accordingly, low DIO3 mRNA levels were associated with an increased risk of death in a multivariate model in the validation cohort. DNA methylation analysis revealed that the DIO3 gene promoter is hypermethylated in tumors when compared to normal tissue. In conclusion, DIO3 is expressed in normal and tumoral breast tissue, while decreased expression relates to poor overall survival in breast cancer patients. Finally, loss of DIO3 expression is associated with hypermethylation of the gene promoter and might have therapeutic implications. [ABSTRACT FROM AUTHOR]