The potential diagnostic value of Rac1 immunohistochemistry in follicular thyroid carcinoma.

INTRODUCTION: Rac1 and Galectin-3 has been suggested to involve in the invasion and aggressive behaviour of several cancers. The aim of this study is to evaluate the immunoreactivity of Rac1 and Galectin-3 in follicular adenoma (FA) and follicular thyroid carcinoma (FC) in an attempt to investigate its association with the invasion of FC and its immunohistochemical diagnostic value to discriminate FA and FC. MATERIALS AND METHODS: This study included 120 selected paraffin embedded tissue blocks from surgically resected follicular thyroid neoplasms, consists of 60 cases of FA and 60 cases of FC. Immunohistochemistry staining for Rac1 and Galectin-3 were performed on all cases. The diagnostic value of these immunohistochemical markers to determine invasion in FC were calculated. RESULTS: Positive immunoreactivity of Rac1 were found in 25/60 (41.67%) cases of FA and 56/60 (93.3%) cases of FC (p=0.0001). Positive immunoreactivity of Galectin-3 was found in 8/60 (13.3%) cases of FA and 47/60 (78.3%) cases of FC (p=0.0001). The sensitivity of Rac1 in distinguishing FA from FC were 93.3% with specificity, PPV, NPV, and overall accuracy were 58.3%, 69.1%, 89.7%, and 75.8% consecutively. The sensitivity of combination Rac1 and Galectin-3 were 73.3% with specificity, PPV, NPV, and overall accuracy were 96.7%, 95.7%, 78.4%, and 85% consecutively. CONCLUSIONS: Rac1 immunohistochemistry is a sensitive marker in discriminating FA from FC, but its specificity and accuracy are low. Combination of Rac1 and Galectin-3 gives more specific and higher diagnostic accuracy. Combination of Rac1 and Galectin-3 may be useful to determine invasion and diagnose FC.

Rationale behind using valproic acid for Non-Hodgkin lymphoma: a biomolecular perspective.

OBJECTIVE: Non-Hodgkin lymphoma (NHL) is a hematological malignancy with a high rate of relapse and refractory cases. It is believed to be caused by resistance to standard treatment modalities. Valproic acid (VPA), previously used as a broad-spectrum anticonvulsant drug, has been proposed for NHL owing to its action of epigenetic modification by inhibiting histone deacetylase. However, VPA studies on NHL are limited. This review describes the rationale behind the use of VPA for NHL treatment, particularly focusing on its molecular mechanism of action. MATERIALS AND METHODS: This is a narrative review. The literature search strategy for indexed Scopus articles was performed randomly using PubMed and MEDLINE as the primary sources. No specific term was used. RESULTS: Several mechanisms are responsible for NHL development. VPA can modulate these mechanisms via epigenetic and nonepigenetic modifications. It may also have an impact on the proteins responsible for treatment resistance. The mechanisms of action of VPA in NHL are as follows: the induction of cell cycle arrest via the upregulation of cyclin-dependent protein kinase inhibitors; induction of Apo2 ligand or tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis; inactivation of B-cell lymphoma 6; inhibition of Janus kinase/signal transducer and activator of transcription, phosphoinositide 3-kinase/Akt, and nuclear factor kappa B signaling pathways; upregulation of tumor antigen as the primary target of immunotherapy; and strengthening of tumor immunosurveillance. CONCLUSIONS: Based on its biomolecular mechanism of action, VPA appears to be a promising initial treatment before initiating the standard treatment in patients with NHL to overcome resistance.