Metformin alleviates neurocognitive impairment in aging via activation of AMPK/BDNF/PI3K pathway.

Slowing down age-related neurocognitive impairment has been a challenge. We evaluated the therapeutic effects of metformin in D-galactose-induced aging. Additionally, we studied the potential molecular mechanisms that could be responsible for metformin's anti-aging effects. Thirty male rats were equally divided into: 1-control group, which received saline solution, 2-D-galactose (D-gal) group, which received D-galactose (100 mg/kg/day) by gastric lavage for eight weeks, and 3-D-galactose + Metformin (D-gal + Met) treated group, which received D-galactose + metformin (200 mg/kg/day) by gastric lavage for eight weeks. Neurocognitive assessment was done. Measurement of inflammatory, oxidative stress, and BDNF biomarkers was performed. AMPK and PI3K genes expression were assessed. Hippocampal tissues were dissected for histopathological and immunohistochemical studies. D-gal resulted in neurocognitive impairments, elevation of inflammatory biomarkers, altered oxidative stress markers, decreased BDNF, decreased expression of synaptophysin and Bcl2 with increased expression of Caspase-3, and down-regulation of AMPK and PI3K genes. Neurodegenerative changes were present in the hippocampus. Metformin restored significantly D-gal induced neurodegenerative changes. We concluded that metformin could alleviate age-induced neurocognitive deficit via amelioration of neuroinflammation, attenuation of oxidative stress, reduction of apoptosis, as well as promotion of synaptic plasticity. These mechanisms could be mediated via the activation of the AMPK/BDNF/PI3K pathway.

Immunohistochemical expression of Axin-2, as an implication of the role of stem cell in scar pathogenesis and prognosis.

BACKGROUND: Wound healing is a multi-phased process. A disruption in these phases could result in a persistent wound or an atypical scar. Wounding activates wingless proteins (Wnt) signaling, which aids in the healing process. Axis inhibition protein-2 regulates a variety of cellular activities through the Wnt and other pathways. AIM: To assess the role of Axin-2 in patients with abnormal scars, using immunohistochemical study. METHODS: This case-control study enrolled a total of 60 participants: 30 patients with abnormal scars (12 hypertrophic scars, 13 atrophic scars, and 5 keloid scars) and 30 age, sex, and site matched, apparently healthy controls. For immunohistochemistry examination of Axin-2 expression, skin samples were obtained from (i) lesional and (ii) perilesional skin of patients with aberrant scars, as well as (iii) normal control's skin. RESULTS: Epidermal Axin-2 expression positivity, cellular topography, intensity, and H score showed significant differences between the groups (p < 0.05). In the dermis (fibroblast/myofibroblast), there were significant differences in Axin-2 expression positivity, location, intensity, and H score (p < 0.001 for all). The epidermal Axin-2 H score and the Manchester scale had a significant positive correlation (r = 0.832, p = 0.001). The epidermal Axin-2 H score and age (r = -0.576, p = 0.001), and the Stony Brook scale (r = -0.419, p = 0.021), had significant negative correlations. CONCLUSION: Axin-2 overexpression might be accused in pathogenesis of abnormal scar and clinical worse scar outcome. In order to deprive scars of their regenerative cell pools, future scar therapies may target Axin-2 as a stem cell marker.

Krox20 expression in abnormal scars: An immunohistochemical study.

BACKGROUND: Scars are the end outcome of healing. They are grouped into several types, the common of which are keloids, hypertrophic, and atrophic scars. The role of Krox20 in skin and hair physiology and pathology had emerged. Overexpression of Krox20 was sufficient to stimulate collagen gene expression and myofibroblast differentiation and is necessary for transforming growth factor-ß (TGF-ß) induced profibrotic responses. OBJECTIVE: To investigate the role of Krox20 in abnormal scar pathogenesis. Hopefully, this insight can set the route for newer therapeutic approaches. MATERIALS AND METHOD: This study was carried out on 30 cases (10 cases of keloids, 10 cases of atrophic scars, and 10 cases with hypertrophic scars [HTS]) and 10 age and gender-matched apparently healthy subjects as a control group. Thirty biopsies were taken from perilesional areas. Evaluation of Krox20 expression was done using standard immunohistochemical technique. RESULTS: Krox20 was downregulated in epidermis of scar biopsies compared with perilesional and normal skin (p = 0.02) while it was overexpressed in fibroblasts in lesional scar biopsies compared with perilesional and normal skin (p < 0.001). Keloid cases have significantly higher Krox20 expression in fibroblasts compared with HTS cases (p < 0.001). Krox20 had significantly nucleocytoplasmic pattern of staining in scar cases compared with normal skin (p < 0.001). CONCLUSION: Krox20 overexpression may have a role in scar pathogenesis through upregulation of multiple genes associated with tissue remodeling and wound healing. This may open an avenue for research for new therapies based on Krox20 inhibition.

Light chain 3 immunoexpression in psoriasis.

Autophagy dysregulation is involved in many diseases. The implication of autophagy in psoriasis pathogenesis is still uncertain. To investigate the role of Light Chain 3 (LC3), a good marker for autophagy, in psoriatic skin based on immunohistochemical study and correlate its expression - for the first time to the best of our knowledge - to clinicopathological data Prospective case-control study was conducted on 60 subjects (30 control, 30 psoriasis patients). Skin biopsies from control, lesional, and perilesional skin were processed for routine histopathological examination and LC3 immunoreaction assessment. There was a significant upregulation of the epidermal and dermal LC3 immunoreaction in the lesional skin compared with the control and perilesional skin specimens (P < .001). A significant positive correlation between the epidermal and dermal LC3 H scores in the lesional and perilesional skin was recorded. There was a non-significant relationship between the H score in the lesional skin and disease severity. LC3 could be considered in psoriasis pathogenesis; however, LC3 was not related to the severity of the disease. The findings might offer a novel target therapy for psoriasis patients.

Therapeutic potential of targeted-gold nanospheres on collagen-induced arthritis in rats.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted-nanoparticles) against collagen-induced arthritis (CIA) and compared the outcomes with conventional methotrexate (MTX) and biological (infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. The bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro-inflammatory/anti-inflammatory and angiogenic mediators' expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres-conjugated with nucleus localized peptide (nuclear membrane-targeted) (AuNSs@NLS) has resolved bone destruction and inflammation compared to gold nanospheres-conjugated at polyethylene glycol (AuNSs@PEG). Although the AuNSs accumulated in different organs in both cases, they did not induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators' expression and induced anti-inflammatory cytokine production, but the AuNSs@NLS had superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane-targeted AuNSs effectively attenuated arthritis progression without systemic side effects.

Countering adipose tissue dysfunction could underlie the superiority of telmisartan in the treatment of obesity-related hypertension.

BACKGROUND: The prevalence of hypertension and obesity has increased significantly in recent decades. Hypertension and obesity often coexist, and both are associated with increased cardiovascular mortality. Obese hypertensive patients usually require special anti-hypertensive treatment strategy due to the increased risk of treatment resistance. Molecules that can target both obesity and hypertension underlying pathologies should get more attention. Herein, we evaluated the therapeutic effects of telmisartan, with special interest in visceral adipose tissue dysfunction, in obesity-related hypertension rat model. METHODS: Thirty male Wistar rats weighing 150-200 g were equally divided into: 1-Control group (fed normal laboratory diet for 24 weeks), 2-Diet-induced obesity group (DIO, fed high fat diet for 24 weeks), and 3-Diet-induced obesity treated with telmisartan group (DIO + Tel, fed high fat diet and received telmisartan for 24 weeks). At the end of the study, anthropometrical parameters were evaluated. Systolic blood pressure and heart rate were measured. Blood samples were collected for the measurement of serum lipids, adipokines, cardiac, renal, inflammatory, and oxidative stress biomarkers. Kidneys were removed and used for histopathological studies, and visceral adipose tissue was utilized for histopathological, immunohistochemical and RT-PCR studies. RESULTS: High fat diet resulted in obesity-related changes in anthropometrical parameters, elevation of blood pressure, increase in heart rate, higher serum levels of cardiac, inflammatory and kidney function biomarkers, with altered serum lipids, adipokines and oxidative stress markers. Morphological changes (H&E and PAS-stained sections) were noticed in kidneys and visceral adipose tissue. Immunohistochemistry and RT-PCR studies confirmed adipose tissue dysfunction and over-expression of inflammatory and oxidative stress proteins. Telmisartan countered obesity-induced alterations in cardiovascular, renal, and adipose tissue functions. CONCLUSION: Adipose tissue dysfunction could be the core pathophysiology of obesity-related hypertension. Besides its anti-hypertensive effect, telmisartan had profound actions on visceral adipose tissue structure and function. Attention should be given to polymodal molecules targeting adipose tissue-related disorders.

In Vitro and In Vivo Antitumor Activity of Indolo[2,3-b] Quinolines, Natural Product Analogs from Neocryptolepine Alkaloid.

Neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) analogs were synthesized and evaluated in vitro and in vivo for their effect versus Ehrlich ascites carcinoma (EAC). The analogs showed stronger cytotoxic activity against EAC cells than the reference drug. The in vivo evaluation of the target compounds against EAC-induced solid tumor in the female albino Swiss mice revealed a remarkable decrease in the tumor volume (TV) and hepatic lipid peroxidation. A noticeable increase of both superoxide dismutase (SOD) and catalase (CAT) levels was reported (p < 0.001), which set-forth proof of their antioxidant effect. In addition, the in vitro antioxidant activity of the neocryptolepine analogs was screened out using the DPPH method and showed promising activities activity. The histopathological investigations affirmed that the tested analogs have a remarkable curative effect on solid tumors with minimal side-effect on the liver. The study also includes illustrated mechanism of the antitumor activity at the cell level by flow cytometry. The cell cycle analysis showed that the neocryptolepine analogs extensively increase the aggregation of tumor cells in three phases of the cell cycle (G0/G1, S and G2/M) with the emergence of a hypo-diploid DNA content peak (sub-G1) in the cell cycle experiments, which is a clear-cut for the apoptotic cell population. Furthermore, the immunological study manifested a significant elevation in splenic lymphocyte count (p < 0.001) with the elevation of the responsiveness of lymphocytes to phytohemagglutinin (PHA). These results indicate that these naturally-based neocryptolepine alkaloids exhibit marked antitumor activity in vivo and represent an important lead in the development of natural-based anticancer drugs.

Desmoplastic Fibroma of the Skull in an Infant: A Case Report.

Desmoplastic fibromas are rare benign bone tumors occurring primarily in long bones and mandible. In this case report, we present a desmoplastic fibroma originating from the left frontal bone. This is an exceptionally rare presentation of this pathology and the associated imaging and pathologic slides are highly educational. We discuss the relevance to the literature and how to manage these patients clinically.

Autophagy and mTOR Pathways Mediate the Potential Renoprotective Effects of Vitamin D on Diabetic Nephropathy.

INTRODUCTION: Not only is diabetic nephropathy (DN) the most common cause of end-stage renal disease worldwide, but it also increases the risk of mortality up to fourteen times compared to normoalbuminuric diabetic patients. AIM: The aim of the current study was the evaluation of the renoprotective effects of vitamin D in DN and the possible interplay between autophagy and mTOR pathways. MATERIALS AND METHODS: Fifty male Wistar albino rats were divided (10/group) into control, DN group, insulin-treated DN group, vitamin D-treated DN group, and combined insulin and vitamin D-treated DN group. Assessments of systolic blood pressure, albuminuria, creatinine clearance, serum glucose, insulin, urea, creatinine, inflammatory cytokines, oxidative stress markers, and rat kidney gene expression of mTOR were performed. Histopathological and immunohistochemical assessments of autophagy marker LC3 in rat kidneys were also performed. RESULTS: DN was associated with significant increases in SBP, urinary albumin, serum glucose, urea, creatinine, inflammatory cytokines, MDA, and mTOR gene expression (P < 0.05). However, there was significant decrease in creatinine clearance, serum insulin, GSH, and H score value of LC3 when compared with control group (P < 0.05). The combination of insulin and vitamin D treatment significantly restored DN changes when compared with the other treated groups, except in oxidative stress markers where there was an insignificant difference between the combination-treated and insulin-treated groups (P > 0.05). CONCLUSION: It has been concluded that vitamin D is a potent adjuvant therapy in treatment of DN via downregulation of mTOR gene expression, stimulation of autophagy, and antioxidant, anti-inflammatory, and hypotensive effects.

Does the Autophagy Related Gene 7 (ATG7) Have a Role in Non-Melanoma Skin Cancer?

PURPOSE: To evaluate the role of autophagy related gene 7 (ATG7) in non-melanoma skin cancer. SUBJECTS AND METHODS: This retrospective and prospective case-control study was performed on 104 patients with non-melanoma skin cancer (NMSC) in addition to 20 apparently healthy subjects matched for age and sex as a control group. Multiple skin biopsies were taken for immunohistochemical evaluation of ATG7 expression. RESULTS: Both epithelial and stromal ATG7 were expressed in all participants while all patients showed nucleocytoplasmic localization and controls showed both cytoplasmic and nucleocytoplasmic expression. In addition, significantly higher H-scores of ATG7 in both epithelium and stroma were detected in patients compared to controls (P<0.001). CONCLUSION: ATG7 nucleocytoplasmic topographic localization might be involved in the pathogenesis of NMSC, which can open the gate for new target therapy for this skin cancer.

Role of Janus kinase 1 and signal transducer and activator of transcription 3 in vitiligo.

BACKGROUND: Vitiligo is an acquired autoimmune skin disorder. The often-visible lesions of vitiligo have a major impact on patients' quality of life and the results of the treatment regimens on offer are unsatisfactory, so there is a need for new therapeutic regimens. Recent advances in vitiligo pathogenesis have led to recognition of the importance of the JAK-STAT pathway as an attractive therapeutic option. PURPOSE: To evaluate role of JAK1 and STAT3 in vitiligo. METHODS: This prospective case-control study was carried out on 35 patients presenting with vitiligo and 20 apparently healthy age- and sex-matched volunteers. Skin biopsies from controls and cases were taken for histopathological and immunohistochemical JAK1 and STAT3 evaluation. RESULTS: Epidermal and dermal overexpression of STAT3 was noted in lesional skin compared to the other groups (P=0.02 and P<0.001, respectively). There was a positive correlation between dermal expression of JAK1 and dermal expression of STAT3 (r=0.52, P=0.004). CONCLUSION: In conjunction, JAK1 and STAT3 might be involved in the pathogenesis of vitiligo. This could open the gate for the use of JAK1 and STAT3 inhibitors as new targeted therapy for vitiligo.

Immunolocalization of MUC1 in chronic plaque psoriasis.

Psoriasis is a chronic skin inflammatory disease with immunological, hyperproliferative and angiogenic dysfunction. MUC1 is a molecular sensor and signal transductor that responds to external stimuli generating cellular responses, which include cell proliferation, growth, differentiation, migration, invasion, survival and secretion of growth factors, and cytokines. The current study aimed at evaluation of the possible role of MUC1 in the pathogenesis of psoriasis through its immunohistochemical localization in involved and uninvolved psoriatic skin compared to normal skin in addition of correlating MUC1 expression with the clinical and pathological parameters of psoriasis. The current study investigated 30 patients with psoriasis and 10 controls. MUC1 was expressed in epidermis in 30% of normal skin compared to 20% of uninvolved epidermis and 63.3% of involved epidermis of psoriatic skin. MUC1 was seen staining endothelial cells of capillaries and inflammatory cells in dermis in 10% of normal skin, 0% of uninvolved psoriasis, and 83.3% of involved psoriasis. Dermal expression of MUC1 in psoriasis was associated with mild to moderate degrees of epidermal acanthosis (p = .027). Intense MUC1 expression by psoriatic epidermis was associated with short disease duration (p = .044). The upregulation of MUC1 in involved psoriatic lesion compared to uninvolved and normal skin may suggest MUC1 role in pathogenesis of psoriasis especially early stages. MUC1 may be responsible for less severity of psoriasis in old aged patients.

Immunohistochemical study of janus kinase 1/signal transducer and activator of transcription 3 in psoriasis vulgaris.

Background: Human JAKs are responsible for generating docking sites for human SSTAT phosphorylation. The role of JAKs in psoriasis pathogenesis has not been clearly explained. Aim: To investigate the role of JAK1 in psoriasis pathogenesis and to assess if this role is mediated through STAT3 or not, through evaluation of their immunohistochemical expression in the skin of psoriatic patients. Methods: This case-control study was carried out on 26 patients presenting with psoriasis vulgaris versus 26 age- and sex-matched apparently healthy volunteers. Psoriasis Area and Severity Index (PASI) scores were used to evaluate psoriasis severity. From all controls and cases (lesional and perilesional), skin biopsies were taken for histopathological and immunohistochemical JAK1 and STAT3 evaluation. Results: There was significant stepwise upregulation of JAK1 from controls to perilesional to lesional psoriatic skin of the patient group in both epidermis and dermis (P≤0.001 for both). Dermal JAK1 H-score was significantly associated with psoriasis severity (P=0.01). STAT3 was significantly overexpressed in lesional psoriatic skin over nonlesional skin (P<0.001). There were significant positive correlations between lesional H-scores for STAT3 and Psoriasis Area and Severity Index scores in epidermis (r=0.63, P<0.001), and in dermis (r=0.47, P=0.04). There was a significant positive correlation between JAK1 and STAT3 expression in epidermal lesional psoriatic skin (r=0.44, P=0.03). Conclusion: JAK1 has a proinflammatory effect in psoriasis pathogenesis, which could be mediated through increasing STAT3 expression in psoriasis. JAK1 and STAT3 tissue expression could be markers of psoriasis severity. JAK1 may be used as a target for immunotherapy in psoriasis-management programs.

Second to fourth digit ratio in female patients with acne vulgaris: Could it be a predictor of androgen receptor status?

BACKGROUND: Second to fourth digit (2D:4D) ratio is the ratio of index to ring fingers length. It reflects prenatal androgen exposure and sensitivity. Androgens are important in the pathogenesis of acne vulgaris, This ratio may therefore be of significance in determining the expression of androgen receptors. AIM: To investigate the relationship between second to fourth digit ratio and androgen receptor expression in female patients with acne vulgaris and to assess its association with clinical aspects of acne vulgaris. METHODS: Females patients (n = 352) with different degrees of acne vulgaris severity and 168 age-matched females were enrolled. Right, left and total second to fourth digit ratios were calculated. Biopsies from all participants were processed for androgen receptor expression by immunohistochemical method. RESULTS: Right, left and total second to fourth digit ratios were significantly lower in acne vulgaris patients than controls (P < 0.001 for all), and each of them had a significant negative correlation with duration of acne vulgaris (P < 0.001; P = 0.013; P < 0.001, respectively). Androgen receptors were detected in epidermal keratinocytes, hair follicles, sebaceous glands and fibroblasts. Right second to fourth digit ratio showed a negative correlation with androgen receptor H score of keratinocytes (r = -0.28;P = 0.02), hair follicles (r = -0.22; P = 0.05) and fibroblasts (r= -0.37;P = 0.001), while left second to fourth digit ratio demonstrated negative correlation with androgen receptor H score of sebocytes (r = -0.397; P < 0.000) only. LIMITATIONS: Lack of follow-up and absence of male participants were the main limitations of this study. CONCLUSION: A masculine second to fourth digit ratio in female patients could anticipate acne vulgaris development, its duration and severity. Moreover, this ratio is associated with an upregulation of cutaneous androgen receptors. Taken together, second to fourth digit ratio could help in designing plans for treatment of acne vulgaris.

Progranulin and beta-catenin in psoriasis: An immunohistochemical study.

BACKGROUND/OBJECTIVES: Progranulin (PGRN) is a secreted glycoprotein that was investigated in many skin diseases. It plays an important role in inflammatory response and autophagy which could be mediated through Wnt/ß-catenin pathway. However, the role of PGRN in pathogenesis of psoriasis has not been clearly well-known. Therefore, we aimed by this study to investigate the possible role of progranulin in psoriasis pathogenesis through evaluation of its immunohistochemical expression in lesional and perilesional skin of psoriasis patients and to investigate if its hypothesized role is mediated through ß-catenin or not. METHODS: This case-control study was carried out on 37 patients presented with variable degrees of psoriasis vulgaris severity vs 37 age and sex-matched apparently healthy volunteers. Psoriasis area and severity index (PASI) score was used to evaluate the severity of psoriasis. From all cases (lesional and perilesional) and controls, skin biopsies were taken for histopathological and immunohistochemical evaluation of PGRN and ß-catenin. RESULTS: There was a significant stepwise upregulation of PGRN from controls (76.2 ± 11.9) to perilesional (178.7 ± 11.8) and lesional (242.7 ± 12.7) psoriatic skin (P < 0.001). PGRN expression was significantly correlated with psoriasis severity (r = 0.61; P < 0.001). ß-catenin showed a significant stepwise downregulation from control (210.0 ± 19.3) to perilesional (131.4 ± 9.2) and lesional (97.3 ± 11.5) psoriatic skin(P < 0.001). There was a significant negative correlation between PGRN and ß-catenin expression in psoriatic skin (P < 0.001). CONCLUSIONS: Progranulin has a pro-inflammatory effect in the psoriasis pathogenesis, which could be mediated through a decreasing ß-catenin expression in psoriasis. PGRN may be used as a target for immunotherapy in psoriasis management program.

Morphometric and ultrastructural analysis of tramadol effects on epididymis: an experimental study.

The effect of tramadol addiction on epididymal structure was not investigated before. Therefore, this experimental study was carried out to investigate the effect of chronic tramadol use on the epididymal structure using light and electron microscopies. Thirty adult Wister Albino male rats were divided into two groups: control group (five rats) and tramadol-treated group (25 rats), which was further subdivided into five subgroups that received tramadol orally at 4.5, 9, 45, 90, and 135 mg/kg/day, respectively, for 18 weeks. Epididymal tissues were dissected and processed for histopathological examination. Morphometric analysis showed significantly reduced mean values of epididymal ducts' diameters and epithelial height in the tramadol-treated group compared with the control group. Light microscopic examination revealed degeneration and necrosis of epididymal cells in the tramadol-treated group. Electron microscopic (EM) examination showed ultrastructure alterations in a dose-dependent manner. In conclusion, tramadol can adversely affect all epididymal cells, which subsequently deteriorate epididymal function and may affect sperm maturation, leading to subfertility.

The Role of Hepsin in Endometrial Carcinoma.

PURPOSE: Endometrial carcinoma is the sixth most common cancer in women worldwide and the most common invasive cancer of the female genital tract in developed countries. It is hoped that through a better understanding of the alterations implicated in endometrial cancer pathogenesis and prognosis, a more complete profile of risk factors and targeted therapy can be developed. Hepsin is a member of the type II transmembrane serine protease family. The importance of hepsin in prostate cancer has been demonstrated by several studies. However, the role of hepsin in endometrial carcinoma is yet to be identified. This study aimed to evaluate the immunohistochemical expression of hepsin in endometrial carcinoma, trying to explore its diagnostic and prognostic value. MATERIALS AND METHODS: This retrospective study was conducted on 27 endometrial carcinoma and 18 endometrial hyperplasia cases. Immunohistochemical expression of hepsin was evaluated in tissue specimens and results were correlated with the available clinicopathlogic parameters. RESULTS: Positive hepsin expression was seen in all (100%) carcinoma and 17/18 (94.44%) endometrial hyperplasia cases. The H-score of hepsin expression in endometrial carcinoma was significantly higher than that of hyperplasia cases (P=0.012). A significant negative association was found between hepsin expression in endometrial carcinoma cases regarding the grade and the size of tumors (P=0.018 and 0.008, respectively) as well as myometrial invasion (P=0.027). CONCLUSIONS: Hepsin could play an important role in the pathogenesis and the early carcinogenesis of endometrial carcinoma and could serve as a prognostic biomarker in this tumor.

Androgen Receptor Expression in Breast Carcinoma of Egyptian Patients.

INTRODUCTION: Breast carcinoma (BC) is a heterogeneous disease, with distinctive molecular sub-types, influencing BC patients prognosis and therapeutic options. Androgen Receptor (AR) is a steroid nuclear receptor involved in complex signaling pathways, that are thought to play a role in cell proliferation. AR expression in relation to different molecular sub-types of BC is not clearly understood. AIM: The aim of this study was to evaluate the expression of AR in BC from Egyptian patients and correlate it with the standard clinico-pathologic variables, molecular sub-type of BC and the Overall Survival (OS). MATERIALS AND METHODS: This retrospective study was conducted on 81 cases of BC from egyptian patients, stained immunohistochemically with AR. Chi-Square and Kaplan-Meier tests were applied to study the correlation between AR expression and clinicopathologic variables and the OS of BC patients respectively. RESULTS: Among studied BC cases, 37.04% were immunoreactive to AR. AR immunoreactivity was significantly corrrelated with older age (p=0.03), post-menopausal status (p=0.001), lower grade (p=0.003), the presence of in-situ component (p= 0.014), early stage of presentation (p=0.03) and good-moderate NPI (0.009). It was also correlated with Positive ER, negative HER-2/neu, low Ki-67 proliferation index and luminal A subtype. AR expression didn't correlate with the OS in the studied cases. CONCLUSION: AR was found to be related to favourable prognostic factors in BC but not to OS. It was particularly expressed in luminal A group and in significant proportion in Triple Negative Breast Carcinoma (TNBC), providing an opportunity for AR targeted therapy.

Overexpression of Carbonic Anhydrase IX is a Dismal Prognostic Marker in Breast Carcinoma in Egyptian Patients.

Carbonic anhydrase IX (CAIX) is an enzyme whose expression is very limited in normal tissues and it is highly expressed in various cancers. Therefore, inhibition of CAIX is considered as a promising therapeutic target for the treatment of solid tumors where hypoxic environment has developed. The aim of the current work is to evaluate the immunohistochemical (IHC) expression of CAIX in breast cancer (BC) of Egyptian patients and to investigate the associations of CAIX expression with the standard clinicopathologic features, IHC subtypes of BC, and overall survival. This retrospective study was conducted on 56 archival cases of Egyptian BC patients. Fifty-one of 56 cases (91.1%) showed positive expression of CAIX with cytoplasmic localization, whereas 5 cases (8.9%) showed negative expression. CAIX IHC overexpression is significantly associated with advanced stage and presence of coagulative tumor cell necrosis (P=0.03 and 0.02, respectively). Multivariate analysis revealed Ki67 labeling index and CAIX H-score grouping (P=0.03 and 0.02, respectively) as independent prognostic factors affecting BC patients' overall survival. We concluded that CAIX could play a role in the progression of the studied BC cases. CAIX is a good candidate for target therapy.