Chronic Lymphocytic Thyroiditis with Oncocytic Metaplasia Influences PD-L1 Expression in Papillary Thyroid Carcinoma.

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.

Immunohistochemical and clinicopathologic features of estrogen receptor-negative, progesterone receptor-positive, HER-2 negative breast carcinomas.

OBJECTIVE: Currently, there is an ongoing debate whether progesterone receptor positive and estrogen receptor negative breast carcinomas represent a true distinct subtype of tumor or a mere immunohistochemical artifact. In this study, we conducted an immunohistochemistry panel with the antibodies TFF1, EGFR, and CK5 to reclassify this phenotype in a luminal or basal-like subtype. METHODS: Tumors estrogen receptor -/progesterone receptor +, Her-2 - from a large population of breast cancer patients were selected to be studied. Immunohistochemistry with the antibodies TFF1, EGFR, and CK5 was performed. Tumors showing positivity for TFF1, regardless of EGFR and CK5 results, were classified as luminal-like carcinomas. Those lesions that were negative for TFF1, but were positive for EGFR and/or CK5, were classified as basal-like triple-negative carcinomas. When the three markers were negative, tumors were classified as undetermined. Clinical pathologic characteristics of patients and tumor recurrence were evaluated. RESULTS: Out of 1188 breast carcinomas investigated, 30 cases (2.5%) presented the estrogen receptor -/progesterone receptor +/HER2- phenotype. Of them, 27 tumors (90%) were classified as basal-like triple-negative carcinomas, one as luminal-like (3.3%), and two as undetermined tumors (6.7%). The mean follow-up for the study group was 27.7 (2.7 to 50) months. Out of the 26 patients, 6 had cancer recurrence: 2 local and 4 systemic recurrences. The average time for recurrence was 17 (8 to 38) months. CONCLUSION: Estrogen receptor -/progesterone receptor +/tumors exhibit aggressive behavior, similar to triple-negative tumors. An appropriate categorization of these tumors should be made to improve their therapeutic management.

Overexpression of PIK3CA impacts global survival of patients with HER2 subtype breast carcinoma.

PURPOSE: To investigate the expression of proteins fosfatidilinositol-4,5-bifosfate 3-quinase (PIK3CA) and phosphatase and tensin homolog (PTEN) in HER2-positive breast cancer and verify their associations with clinical and pathological variables. METHODS: We assessed PTEN and PIK3CA status using immunohistochemistry (IHC), which was performed in formalin-fixed paraffin-embedded biopsies from 50 patients with HER2-positive breast cancer. Medical records were studied for collection of clinical-pathological information, including overall survival (OS). The HIC markers PTEN and PIK3CA were analyzed semi-quantitatively by two blinded independent researchers. The relationship between the variables were evaluated using the chi-square test and Kaplan-Meier curves plus log-rank test for survival. RESULTS: In IHC, the expression level of PIK3CA was 86%, and loss of PTEN expression was observed in 46% of the cases. The expression of the markers showed no significant correlation with each other or with the clinical and pathological parameters studied: tumor grade, staging, ER, PR, Ki67 and recurrence. The highest expression of PIK3CA was associated with lower number of deaths (p=0.016) and longer OS of patients (p=0.001). The PTEN marker showed no significant effect on OS. CONCLUSIONS: The PIK3CA expression showed a protective effect in relation to the OS of patients with HER2-positive breast cancer.

African-derived South American populations: A history of symmetrical and asymmetrical matings according to sex revealed by bi- and uni-parental genetic markers.

Estimates of African, European, and Amerindian contributions to the gene pool of 11 predominantly African-derived South American populations were obtained using five autosomal and one Y chromosome hypervariable loci, as well as mitochondrial DNA (sequences of the first hypervariable segment of the control region, plus two restriction sites and the presence or absence of the CoII/tRNA(Lys) intergenic 9-bp deletion). The three latter characteristics are reported here for the first time for 42 individuals living in three Brazilian populations. Thirty-eight sequences were identified in these persons; 17 (45%) could be classified as being of African, 4 (11%) of Amerindian, and 2 (5%) of European origin. Evidence for asymmetrical matings in relation to sex and ethnic group was obtained for nine of the 11 populations. The most consistent finding was the introduction of European genes through males, but the results differ in the several communities, indicating the importance of local factors in such interactions. Am. J. Hum. Biol. 11:551-563, 1999. Copyright 1999 Wiley-Liss, Inc.