Immunohistochemical signaling pathways of triple negative and triple positive breast cancers: What is new?

BACKGROUND: Breast cancer (BC) is a heterogeneous disease with different clinically heterogeneous phenotypes. Triple negative BC (TNBC) (ER-/PR-/HER2-) and triple positive BC (TPBC) (ER+/PR+/HER2+) are characterized by unique clinical behavior and therapeutic challenges. However, their exact molecular pathogenesis is not well studied. This study aims to evaluate the immunohistochemical expression of androgen receptor (AR) and c-Myc in TPBCs and TNBCs, correlate their expression with the clinicopathologic features, and assess the correlation between AR and c-Myc expression in TPBCs and TNBCs. MATERIAL AND METHODS: AR and c-Myc were immunohistochemically assessed in 45 TNBC and 15 TPBC specimens. RESULTS: AR expression was detected in 17.7% of TNBC and in all TPBC specimens. c-Myc was expressed in 46.7% of TNBC and in all TPBC specimens. AR and c-Myc expression in TNBC was not associated with any of the clinicopathological features. In TPBC, AR expression was higher in older age, larger size, higher stage, and lymph node metastasis while c-Myc expression was higher in tumors with perineural invasion. This is the first study that reported a significant positive correlation between AR and c-Myc expression in TNBC and TPBC. CONCLUSION: The current results suggested that AR and c-Myc proteins may contribute to the pathogenesis of TNBC and TPBC. The positive correlation between the two proteins in these subtypes sheds new light on a distinct pathway by which BC cells can modulate their proliferation. Targeting both molecules may provide new therapeutic approaches to improve therapeutic sensitivity and patients' outcomes of these subtypes.

Identification of Genotypes and Allelic Frequencies of Vitamin D Receptor Gene Polymorphism (TaqI) in Egyptian Melasma Patients.

BACKGROUND: Melasma is a characteristic pattern of facial hyperpigmentation, occurring primarily on the forehead, cheeks, and chin, in a mask-like distribution. The pathogenesis of melasma is not fully understood. Vitamin D plays a role in skin pigmentation. It exerts its effect through vitamin D receptor (VDR), which is expressed in variable cells including normal melanocytes. AIM AND OBJECTIVE: The aim of the current work was to investigate if VDR gene polymorphism (TaqI) confers susceptibility to melasma in Egyptian patients. MATERIALS AND METHODS: A total of 45 female patients with melasma were recruited and 50 healthy subjects that were matched on age, sex, body mass index, and skin phototype, were included as a control group. TaqI polymorphism was investigated using restriction fragment length polymorphism polymerase chain reaction (RFLP PCR). RESULTS: Presence of (t) allele and (tt) genotype was significantly associated with melasma cases compared with control group (P < 0.001 for both). No significant association was found between (tt) genotype or (t) allele and clinical data of the studied cases. CONCLUSION: TaqI polymorphism is associated with melasma. Further, large-scale studies are recommended to underscore and validate the current findings. It is also necessary for future studies to extend the research to other populations and ethnicities. Investigating other VDR gene polymorphisms in melasma is also warranted. Since melasma is a multifactorial disease, gene-gene and gene-environment interactions should be considered in future genetic-epidemiologic researches to apply more comprehensive insight into the role of VDR gene in its pathogenesis.

BCL6 mRNA Expression Level in Invasive Duct Carcinoma not otherwise Specified.

INTRODUCTION: B-Cell Lymphoma 6 (BCL6) has an oncogenic role in tumourigenesis of various malignancies. It represses genes involved in terminal differentiation and plays complementary role with Signal Transducer and Activator of Transcription 3 (STAT3) in triple-negative breast cancer cellular function. AIM: To evaluate the expression of BCL6 in cancer breast and determine its correlation with the clinico-pathological features including the molecular subtype of breast carcinoma. MATERIALS AND METHODS: This prospective case control study was carried out on 150 patients, divided into 100 cases of invasive duct carcinoma not otherwise specified and 50 benign breast lesions including fibroadenoma and fibrocystic disease. Fresh tissues were excised, which were then subjected to RNA extraction. The BCL6 mRNA level was assessed using real-time reverse transcription Polymerase Chain Reaction (PCR). RESULTS: There was a significant higher levels of BCL6 mRNA in malignant cases compared to benign ones (p<0.001). The level of BCL6 mRNA was higher in cases showing advanced tumor stage (p<0.04), triple negative subtype and associated in situ component (p<0.001) compared to cases with an early stage, luminal or Her 2-neu positive subtypes and those lacking in situ component. CONCLUSION: BCL6 is up-regulated in breast cancer and is associated with poor prognostic features such as advanced stage and triple negative molecular subtype. BCL6 inhibitors might be considered as targeted therapy for breast cancer.