Clinical significance of histone deacetylase (HDAC)-1, HDAC-2, HDAC-4, and HDAC-6 expression in human malignant and benign thyroid lesions

Abstract

Histone deacetylases (HDACs) have been associated with human malignant tumor development and progression, and HDAC inhibitors are currently being explored as anticancer agents in clinical trials. The present study aimed to evaluate the clinical significance of HDAC-1, HDAC-2, HDAC-4, and HDAC-6 proteins' expression in human malignant and benign thyroid lesions. HDAC-1, HDAC-2, HDAC-4, and HDAC-6 proteins' expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 74 patients with benign and malignant thyroid lesions. Enhanced HDAC-2 and HDAC-6 expression was significantly more frequently observed in malignant, compared to benign, thyroid lesions (p = 0.0042 and p = 0.0069, respectively). Enhanced HDAC-2, HDAC-4, and HDAC-6 expression was significantly more frequently observed in cases with papillary carcinoma compared to hyperplastic nodules (p = 0.0065, p = 0.0394, and p = 0.0061, respectively). In malignant thyroid lesions, HDAC-1, HDAC-4, and HDAC-6 expression was significantly associated with tumor size (p = 0.0169, p = 0.0056, and p = 0.0234, respectively); HDAC-2 expression with lymphatic and vascular invasion (p = 0.0299 and p = 0.0391, respectively); and HDAC-4 expression with capsular invasion (p = 0.0464). The cellular pattern of HDAC-1 and HDAC-2 distribution (nuclear vs. nuclear and cytoplasmic) presented a distinct discrimination between malignant and benign thyroid lesions (p = 0.0030 and p = 0.0028, respectively) as well as between papillary carcinoma and hyperplastic nodules (p = 0.0036 and p = 0.0028, respectively). HDAC-1, HDAC-2, HDAC-4, and HDAC-6 may be associated with the malignant thyroid transformation and could be considered as useful biomarkers and possible therapeutic targets in this neoplasia.

Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients

“…[19,36]. A mouse anti-human Ki-67 antigen; IgG1k antibody (clone MIB-1, Dakopatts, Glostrup, Denmark) were used to evaluate the tumor cells' proliferative capacity [36,37]. The expression of ER, PR and HER2 was assessed immunohistochemically, as previously described [38].…”

“…Finally, HuR and COX-2 expression was classified as low; if the total score was 0 or 2 and high; if the total score was ≥3. In this way, we ensure that each group has a more homogeneous and sufficient number of cases in order to be comparable with the other groups [19,36,37,39]. Staining for ER and PR was evaluated according to CAP/ ASCO recommendations, i.e.…”

“…The fraction of HER2 positive stained cells was scored according to CAP/ASCO guidelines [41]. Ki-67 immunoreactivity was classified according to the percentage of positively stained breast cancer cells exceeded the median percentage value into two categories (below and over mean value), as previously reported [19,36,37,39].…”

Baseline HDAC6 and TFF3 proteins overexpression as prognostic markers of lupus nephritis relapse

“…The intensity of staining was assessed as follows: 0 (no staining);1 (mild staining);2 (intermediate staining) and 3 (intense staining). The proteins' expression was classified as low (total score <3) and high (total score ≥3) (19,20).…”

Histone Deacetylase Inhibitors: A Novel Therapeutic Weapon Αgainst Medullary Thyroid Cancer?

“…In addition, HDAC activity is enhanced in both malignant and benign neoplasms (7). There are several HDAC groups among which HDAC-1, -4, -6 are related to tumor size; HDAC is also related to capsular invasion and HDAC-2 is related to lymphatic and vascular invasion in malignant neoplasms (14). It is now obvious why the use of HDAC inhibitors (HDACIs) appears promising in treating various neoplasms.…”