Immunohistochemical Expression of Angiotensin-Converting Enzyme 2 in the Skin of Patients Affected by COVID-19.

BACKGROUND: After many recorded cases of acute pneumonia of unknown cause, the World Health Organization announced COVID-19 as the start of a new coronavirus disease pandemic in 2019. Angiotensin-converting enzyme-2 (ACE2) is reduced by a protease known as transmembrane serine type 2 in the host cell, which then activates the S protein of SARS-CoV-2 regulating coronavirus entry into the host cells. AIM: The aim of this study was to assess the immunohistochemical expression of ACE 2 in the skin of patients affected by COVID-19 with and without cutaneous manifestations and to correlate ACE2 expression with clinical and pathologic parameters. METHODS: Skin biopsies were obtained from skin lesions of 25 patients presenting with cutaneous manifestations and from the left forearm of 22 patients without cutaneous manifestations. The specimens were processed for evaluation of histopathologic changes and ACE2 immunohistochemical evaluation. RESULTS: Positive ACE2 expression was significantly higher in patients without cutaneous manifestations (96%) than those with cutaneous manifestations (72.7%). Positive ACE2 expression in the skin of affected patients was significantly associated with the presence of comorbidities, positive family history, high ABCD score, elevated lactate dehydrogenase, high D-dimer, rapid respiratory rate, and low oxygen saturation. CONCLUSIONS: The skin could be involved in COVID-19 infection in the form of inflammatory changes, such as pityriasis rosea-like lesions. Patients with COVID-19 who presented with cutaneous manifestations are usually less severe. The presence of ACE2 in the skin of patients with COVID-19 is an indicator of worse status. Patients with COVID-19 without skin manifestations showed higher positivity for ACE2, which may explain the severity of the cases.

Impact of immunohistochemical expression of kinesin family member 18A (Kif18A) and ß-catenin in infiltrating breast carcinoma of no special type.

BACKGROUND: KIF18A is a regulator of the cell cycle that stimulates the proliferation of cancer cells. The Wnt/ß-catenin pathway is involved in different issues' carcinogenesis and is being examined as a therapeutic target. The relationship between KIF18A and ß-catenin in breast cancer was not previously investigated. Therefore, this work aims to study the immunohistochemical expression and correlation of KIF18A and ß-catenin in breast-infiltrating duct carcinoma (IDC) and their relation to prognosis. MATERIAL AND METHODS: Slides cut from paraffin blocks of 135 IDC and 40 normal breast tissues were stained by KIF18A and ß-catenin antibodies. KIF18A cytoplasmic or nucleocytoplasmic staining and ß-catenin aberrant expression either nucleo-cytoplasmic or cytoplasmic staining were considered. RESULTS: Normal breast tissue and IDC showed a significant difference regarding KIF18A and aberrant ß-catenin expression. High KIF18A and ß-catenin H score values were associated with poor prognostic factors such as high grade, advanced stage, distant metastasis, high Ki67 status, and Her2neu-enriched subtype. There was a significant direct correlation between KIF18A and ß-catenin as regards percent and H score values. Prolonged overall survival (OS) was significantly associated with mild intensity and low H score of KIF18A, and low ß-catenin H score. CONCLUSIONS: KIF18A could be involved in breast carcinogenesis by activating ß-catenin. Overexpression of KIF18A and aberrant expression of ß-catenin are considered proto-oncogenes of breast cancer development. KIF18A and ß-catenin could be poor prognostic markers and predictors of aggressive behavior of breast cancer.

Stratification of urinary bladder carcinoma based on immunohistochemical expression of CK5, CK14 and CK20.

Molecular subtyping of urothelial carcinoma (UC) is similar to that of breast cancer and is based on the developmental biology approach. The aim of the present study is to assess the prognostic impact of CK5, CK14, and CK20 expression in urinary bladder cancer (UBC) with the potential to stratify them into different subtypes. The current study examined the immunohistochemical expression of CK5, CK14, and CK20 in 90 specimens of UBC. CK5 was expressed in 81.1% of the cases and was significantly associated with old age, muscle invasion, presence of bilharziasis, and tendency for poor overall survival. CK20 was expressed in 47.8% of the cases and was associated with nonmuscle invasion and pure UC while 50% of the cases expressed CK14 that were associated with muscle invasion and perineural invasion. Most squamous cell carcinoma and those associated with bilharziasis were belonged to Ck5+/CK20- subgroup while pure UC and those lacked bilharziasis were located in the Ck5+/CK20+ subgroup. The basal group (Ck5+/CK14+/CK20-) showed high proliferative features compared to the intermediate group (Ck5+/CK14-/CK20-). Generally, presence of CK5 is associated with adverse features especially in the group lacking CK20; however, basal and intermediate subgroups share CK5 expression but they show different proliferative capacities, so their distinction by CK14 is helpful.

Correlation between immunohistochemical expression of Ki-67and P63 and aggressiveness of urinary bladder urothelial carcinoma.

Urothelial carcinoma is the most common urinary malignancy with a wide proportion of cancer morbidity and mortality. The aim of the present study is to evaluate Ki-67 and p63 immunoexpression and their correlation with grade and stage of bladder urothelial carcinoma. Fifty cases of bladder urothelial carcinoma were investigated and were submitted to immunohistochemical staining for p63 and Ki-67, which were assessed qualitatively and quantitatively. A high percentage of p63 immunoexpression showed a significant association with low-grade tumors (P < .05), while Ki-67 mean percentage of expression was higher in high-grade tumors, advanced stage and multiple tumors compared to low grade, early-stage and single tumors without statistical association. Furthermore, the mean percentage of p63 was higher in urothelial carcinoma with squamous differentiation compared to pure urothelial carcinoma with an absence of statistical significance. P63 could help in the identification of bladder tumors with squamous differentiation since identifying these cases is important regarding prognostic and therapeutic aspects. Ki 67 seems to be associated with features of bladder tumor progression as multiplicity, high grade and advanced stage.

Stratification of urothelial bladder carcinoma depending on immunohistochemical expression of GATA3 and CK5/6.

Bladder urothelial carcinoma (BUC) has two pathways with distinct molecular features and prognosis, non-muscle invasive (NMI) and muscle invasive (MI) tumors. The aim is to investigate the expression of GATA3 and CK5/6 in BUC with correlation to clinicopathologic parameters, including their impact on survival beside their potential use to stratify cases into prognostic subgroups. This study included 80 cases of BUC stained immunohistochemically by GATA3 and CK5/6. The cases were divided into four groups regarding expression status of both markers (luminal, basal, mixed, and null). GATA3 percentage of expression decreased in urothelial carcinoma with squamous differentiation, MI tumors, high-grade tumors, tumors with involved lymph nodes, presence of perineural invasion, presence of bilharziasis, presence of lympho-vascular invasion, and high mitotic count. CK5/6 positivity was higher in urothelial carcinoma cases with squamous differentiation, MI tumors, and presence of perineural invasion. Pure urothelial carcinoma and NMI were in favor of luminal group (GATA3 +ve/CK5/6 -ve). Univariate analysis showed that the presence of bilharziasis was associated with shorter PFS (p = .04). GATA3 and CK5/6 could be used for the stratification of urothelial bladder carcinoma into subtypes with different characteristics. Luminal bladder cancer represents the most common type (60%) that carries favorable features. Bilharziasis-associated urothelial carcinoma carries poor outcome manifested by short PFS.

Effect of L-carnitine and atorvastatin on a rat model of ischemia-reperfusion injury of spinal cord.

Pro-inflammatory cytokines and reactive oxygen species (ROS) are produced in acute spinal cord injury, leading to myelin breakdown, inflammation, mitochondrial dysfunction, and apoptosis of neurons and glial cells. The aim of the present study was to investigate possible protective effects of L-carnitine (carn) or atorvastatin (ator) on spinal cord ischemia-reperfusion injury (IRI). Rats were randomized into nine equal groups (n = 8): control and control taking carn (100 mg/kg BW), ator (2.5 mg/kg BW) or both, as well as sham-operation, IRI and IRI taking same doses of carn, ator or both. Neurological assessments were done 48 hours after IRI, and serum nitrite/nitrate was measured. Finally, lumbar segments of spinal cord were excised, and part was homogenized and prepared for measuring tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), malondialdehyde (MDA), advanced oxidation protein products (AOPP), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase. The other part was sectioned for evaluation of histopathological changes and for immunostaining by glial fibrillary acidic protein (GFAP), Bax and Bcl-2. The IRI increased ROS (nitrite/nitrate, MDA, AOPP) and pro-inflammatory cytokines (TNF-α, IL-1ß), and decreased antioxidants (GSH, GPx, SOD, catalase) with impaired sensory and motor functions. Astrogliosis was detected by GFAP, and increased apoptosis was demonstrated by increasing Bax and decreasing Bcl-2. Treatment with carn or ator alone decreased TNF-α, IL-1ß, nitrite/nitrate, MDA and AOPP, and increased GSH, GPx, SOD, and catalase with improvement of neurological functions and histological studies. Combination of carn and ator improved most of measured IRI-affected parameters better than isolated carn or ator administration.

Immunohistochemical expression of BCAP 31 in chronic plaque psoriasis.

Psoriasis is a common chronic skin inflammatory disease characterized by an exaggerated proliferation of keratinocytes. B-cell receptor-associated protein 31 (BCAP 31) plays critical roles in induction of proliferation and apoptosis. The current study aimed at evaluation of the immunohistochemical localization of BCAP 31 in psoriatic skin compared to normal skin in addition of correlating BCAP31 expression with the clinical and pathological parameters of psoriasis. The present study was carried out on skin biopsies from 30 psoriatic patients and 10 normal skin (control group). BCAP31 was not expressed in normal skin either epidermis or dermis, while it was expressed in epidermis of 15 psoriatic cases and in dermis of 13 cases with a significant difference between the two groups (p < .05). Strong epidermal BCAP 31 expression was associated with marked parakeratosis (p = .025). There was a significant co-parallel epidermal and dermal expression of BCAP31 in psoriasis (p < .05). The role of BCAP 31 is not only confined to its expression by affected keratinocytes but extended to its localization to dermal lymphocytes where they were correlated with each other. The up- regulation of BCAP 31 in psoriatic lesion compared to normal skin may suggest its use as a target therapy for treatment of psoriasis that necessitates further studies to clarify.

Hepatoprotective effect of artichoke leaf extracts in comparison with silymarin on acetaminophen-induced hepatotoxicity in mice.

Acetaminophen is a common analgesic-antipyretic agent, which is safe in therapeutic doses but in higher doses can produce hepatic necrosis. The aim of this study is to investigate the hepatoprotective effects of artichoke, silymarin, and both agents in acetaminophen-induced liver damage in mice. Forty male mice were divided into five main groups, (1) control (2) Acetaminophen (APAP) (3) Artichoke leaf extracts (ALE) and APAP (4) silymarin and APAP group (5) ALE, silymarin and APAP groups. Blood samples were collected for the measurement of liver enzymes (ALT, AST, and ALP). The liver was excised, weighed and dissected into two parts, one used for measurement of malondialdehyde (MDA) and glutathione reductase, and the other part used for histopathological examination and assessment of proliferative cell nuclear antigen (PCNA) immunohistochemical expression. APAP group showed a significant increase in liver weight, ALT, AST, ALP, MDA, and PCNA expression with a significant decrease in glutathione reductase in comparison to control group. All these parameters were significantly improved in the three treated groups when compared to APAP group. APAP group showed marked portal inflammation and parenchyma necrosis. Co-administration of ALE and/or silymarin to acetaminophen treated mice showed a significant reduction in PCNA expression compared to APAP group. Both ALE and silymarin co-treatment showed a significant decrease in PCNA percentage to a level near to control group. Artichoke and/or silymarin are suggested to protect against acetaminophen-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect, decreasing liver damage and proliferation.Abbreviation: ALT, alanine transaminase. AST, aspartate transaminase. ALP, alkaline phosphatase.MDA, malondialdehyde. PCNA, proliferative cell nuclear antigen.

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.

Evaluation of the diagnostic value of emerin and CD56 in papillary thyroid carcinoma - an immunohistochemical study.

Papillary thyroid carcinoma (PTC) is diagnosed in both cytological and histological specimens on the basis of distinct nuclear morphology. These features may not be prominent in some PTC variants and may be seen in some benign conditions. It is necessary to differentiate PTC from other neoplastic and nonneoplastic lesions since it affects treatment strategy and patients' fate. Emerin is a type II integral membrane protein of the inner nuclear membrane that has a characteristic staining pattern in PTC. CD56 is a homophilic membrane glycoprotein that is expressed in thyroid follicular epithelial cells and adrenal glands. The aim of this study was to evaluate the diagnostic value of emerin (positivity, percentage, and highlighting nuclear features) and CD56 (positive versus negative) both singly and in combination for differentiation of PTC from other neoplastic and nonneoplastic mimics. This study was performed on 50 cases of PTC, 9 cases of follicular adenoma (FA), and 12 cases of nonneoplastic thyroid lesions using immunohistochemistry for detection of emerin and CD56. Positive emerin expression was seen in 82% of PTC and in 16.7% of nonneoplastic cases with an absence of expression in FA. CD56 was expressed in 88.9% of FA, 91.7% of nonneoplastic cases and in a minority of PTC cases (6%). Positive emerin revealed 82% sensitivity and 90% specificity, while emerin-highlighted nuclear changes was more specific (95%). Negative CD56 expression revealed 84% sensitivity and 90% specificity. Combined positive emerin (including highlighting nuclear changes) and negative CD56 showed 72% sensitivity and 100% specificity. Positive emerin expression (moderate/strong) and its highlighting nuclear changes combined with negative CD56 could be a very helpful procedure in difficult and overlapping cases with high diagnostic validity (high specificity and positive predictive value).

C-Jun expression in lichen planus, psoriasis, and cutaneous squamous cell carcinoma, an immunohistochemical study.

The AP-1 transcription factor complex is a key player in regulating inflammatory processes, cell proliferation, differentiation, and cell transformation. The aim of the present study is to investigate C-Jun (one of AP-1complex) expression and its proliferative role in skin samples of lichen planus, psoriasis as common inflammatory skin diseases and squamous cell carcinoma using immunohistochemical method. The present study was carried out on skin biopsies of 15 psoriatic patients, 15 lichen planus patients, 15 SCC, and 15 normal skin biopsies. Nuclear expression of C-Jun was detected in basal and few suprabasal layers of epidermis of normal skin. C-Jun was expressed in the whole epidermal layers of both psoriasis (14/15) and lichen planus (15/15) in addition to its expression in lymphocytic infiltrate in the latter in about half of cases (8/15). C-Jun was also expressed in 93.3% (14/15) of SCC in a percentage lower than that of psoriasis, lichen planus, and normal skin. The percentage of C-Jun expression in SCC was significantly associated with an early stage (p = 0.000), free surgical margins (p = 0.022), and small tumour size (p = 0.003). CONCLUSIONS: The marked reduction of C-Jun in SCC in comparison to normal skin and inflammatory skin dermatoses may refer to its tumour suppressor activity. C-Jun expression in SCC carries favourable prognosis. Absence of significant association between C-Jun and Ki-67 either in SCC or inflammatory skin diseases indicates that it does not affect proliferative capacity of cells.

Immunohistochemical expression HIF1α in chronic plaque psoriasis, an association with angiogenesis and proliferation.

Psoriasis is characterized by excessive cell proliferation, angiogenesis, and regions of hypoxia. Hypoxia stimulates production of hypoxia inducible factors (HIFs) such as HIF1α. The aim of the present study is to investigate the possible role of HIF1α in pathogenesis of psoriasis and to correlate its expression with angiogenesis and proliferation in involved and uninvolved skin in patients with plaque psoriasis using CD34 and Ki-67. The current study was performed on 40 skin specimens of patients presented with chronic plaque psoriasis both involved and uninvolved together with 40 specimens from age- and sex-matched healthy volunteers as a control group. The specimens were submitted for HIF1α, CD34, and Ki-67 immunostaining. HIF1α was expressed in 37.5% of normal skin with mild intensity and cytoplasmic localization instead of its expression in 72.5% and 100% of uninvolved and involved psoriatic skin, respectively. Nucleocytoplasmic pattern of HIF1α was seen in 34.5% and 37.5% of uninvolved and involved psoriatic skin, respectively. Positive and intense expression of HIF1α as well as its nucleocytoplasmic localization were significantly in favor of psoriatic skin either involved or uninvolved in comparison to normal skin (P < 0.05). Intense HIF1α was significantly associated with microvessel density in both involved and uninvolved skin (P < 0.05). Nucleocytoplasmic pattern was significantly associated with epidermal acanthosis (P < 0.05) and tended to be associated with percentage of Ki-67 of psoriatic skin (P = 0.06). The present study demonstrated that HIF1α is upregulated in the skin of psoriatic cases (involved and uninvolved) compared to normal skin indicating its role in pathogenesis of psoriasis especially its active nuclear form that showed an association with angiogenesis and proliferation.

Evaluation of the effect and mechanism of action of local phenytoin in treatment of vitiligo.

There are many theories explaining vitiligo such as genetic, autoimmune, neural, free radicals, biochemical, intrinsic defect, melanocytorrhagy, and convergent theories. Phenytoin is a widely used anticonvulsant, which is used in cutaneous medicine for treatment of ulcers and epidermolysis bullosa. The aim of this study is to assess the effectiveness of topical phenytoin gel in the treatment of vitiligo patients and explaining the underlying mechanism using immunohistochemistry for evaluation of HMB45, CD4, and CD8. Only 9 patients out of 28 experienced response to phenytoin in the form of dull, white color change and light brown color. Post-phenytoin treatment biopsies showed decreased density of inflammation, increased melanin and increased HMB45 positive cells together with an increased number of CD4 positive lymphocytes and decreased number of CD8 positive lymphocytes. These observations did not reach significant level (P > 0.05). A high percentage of CD4 positive lymphocytes was significantly associated with a long duration of vitiligo (p = 0.03) and segmental vitiligo type (p = 0.02). The current study applied phenytoin as 2% concentrated gel for 3 months, which is a relatively short duration without observed side effects throughout the period. These results indicate that topical phenytoin of low concentrations may have beneficial effects through immunomodulatory activity by affecting CD4 and CD8 counts and subsequently the ratio between them. Further studies are recommended to combine phenytoin with other antivitiligo agents as local corticosteroids or phototherapy to clarify if it could potentiate their effects.

Immunohistochemical assessment of ezrin and moesin in colorectal carcinoma.

Ezrin and moesin are important molecules of the ERM family of proteins, which regulate cell adhesion and migration. The aim of this study was to evaluate the intensity and pattern of ezrin and moesin expression in colorectal carcinoma (CRC) together with correlating their expression with the clinico-pathologic features of this neoplasm. This study was carried out on 48 CRC and 10 adenoma specimens. All adenoma and 95% of CRC cases showed both ezrin and moesin expression. Ezrin was predominantly cytoplasmic in adenoma cases in comparison to membranous localization in carcinoma cases. Moesin was predominantly expressed in stroma (inflammatory cells and fibroblasts) in carcinoma (89.1%) compared with adenoma (50%). High H-score of ezrin expression was associated with adenocarcinoma type (P = .024) and was inversely correlated with mitotic count (P = .005). High H-score of moesin expression was associated with early Dukes staging of CRC (P = .016), absence of lymph node involvement (P = .022), and low number of involved lymph nodes (P = .04). The association of ezrin with favorable prognostic parameters may be due to its prominent membranous localization. The stroma of CRC could stand against invasion by expression of moesin. Ezrin and moesin are independently expressed from each other.

Immunohistochemical expression of MCM2 in nonmelanoma epithelial skin cancers.

Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent 45.5% and 37.02%, respectively, of total malignant skin cancer according to the latest registry of Egyptian National Cancer Institute. Minichromosome maintenance (MCM) proteins are essential replication initiation factors. The current study examined the immunohistochemical expression of MCM2 in normal skin (10 cases), some proliferative skin lesions (6 psoriasis, 2 keratoacanthoma, and 2 seborrheic keratosis), and nonmelanoma epithelial skin cancers (20 BCC and 21 SCC). MCM2 was expressed in basal layer of normal epidermis and upregulated in proliferative skin lesions and nonmelanoma epithelial skin cancers without significant differences between the latter groups (P > 0.05). Mean and median values of MCM2 percentage of expression in BCC were higher than that of SCC (P = 0.004). MCM2 promotes proliferative capacity of the cells manifested by its expression in basal layer of epidermis, hyperproliferative skin lesions, and malignant cutaneous tumors. Proliferative capacity of BCC may be higher than SCC and this does not necessarily reflect aggressive behavior.

Immunohistochemical study of melanocyte-melanocyte stem cell lineage in vitiligo; a clue to interfollicular melanocyte stem cell reservoir.

There has been a long lasting controversy over whether melanocytes (MCs) in vitiligo are actually lost or still present but functionally inactive. We aimed to evaluate the MC cell lineage in follicular and interfollicular vitiliginous epidermis through immunohistochemical localization of Human Melanoma Black-45 (HMB-45) and Tyrosinase Related Protein 2 (TRP2) and to correlate it with clinicopathologic parameters. Using immunohistochemical techniques, skin biopsies from 50 vitiligo patients and 20 age- and gender-matched healthy subjects were examined. Differentiated active MCs were detected in 44% of interfollicular epidermis (IFE) and 46.7% of follicular epidermis (FE) in lesional skin. Melanocyte precursors/stem cells were detected in 54% of IFE and 63.3% of FE in lesional skin. Melanocyte precursors/stem cells of IFE were significantly associated with residual melanin pigment (p = 0.007) and with absence of angiogenesis (p = 0.05). HMB-45 percentage of expression in IFE was positively correlated with MC precursors/stem cells percentage in FE (r = +0.65, p < 0.001) and IFE (r = +0.33, p = 0.01). Melanocyte precursors/stem cells positivity (p < 0.001) was progressively decreasing with advanced histopathologic grading. There was no significant association between interfollicular or follicular expression of HMB-45, TRP2 or MC precursors/stem cells and the clinical type of vitiligo or its duration. In conclusion, functioning MCs may exist in vitiligo. The presence of MC precursors/stem cells in IFE may provide an additional reservoir needed for repigmentation.

Immunohistochemical expression of aberrant Notch-1 signaling in vitiligo: an implication for pathogenesis.

The etiopathogenetic mechanisms leading to pigment loss in vitiligo are not fully understood. Notch signaling is required for development and maintenance of melanocyte lineage and acts as a key component among keratinocyte-melanocyte interactions. The current study aimed to investigate the possible role of Notch signaling and its effect on the whole melanocyte lineage in vitiligo and correlating it with the different clinicopathologic parameters. Using immunohistochemical technique, Notch-1 expression was evaluated in 50 lesional and 20 perilesional biopsies of patients with vitiligo in comparison with 20 normal skin biopsies as a control group. Lesional biopsies were stained with human melanoma black-45 and tyrosinase-related protein-2 to demonstrate the melanocyte lineage. Membranous and/or nuclear expression of Notch-1 was in favor of control and perilesional skin, whereas cytoplasmic expression appeared only in vitiliginous lesions (P < .05). Membranous and/or nuclear expression of Notch-1 was significantly associated with epidermal human melanoma black-45 positivity (P = .01) and percentage of expression in both epidermis (P = .02) and hair follicles (P = .03) of lesional skin. Cytoplasmic pattern of Notch-1 expression in epidermis was significantly found in lesions with white hair (P = .04) and in cases with marked keratinocyte vacuolization (P = .03). Segmental and acrofacial vitiligo were associated with mild to moderate Notch-1 intensity, whereas generalized vitiligo was associated with strong intensity of expression (P = .02). In conclusion, Notch-1 signaling is inactivated in vitiligo with consequent loss of epidermal and/or follicular active melanocytes. Aberrant Notch signaling in vitiliginous white hair and acral and segmental vitiligo may be the cause of their treatment resistance.

Sebaceous trichofolliculoma of the cheek in a 65-year-old man.

Sebaceous trichofolliculoma is considered as hamartomatous lesion with follicular differentiation. In this study, we demonstrated a classic histopathologic picture of sebaceous trichofolliculoma in a 65-year-old male presented with large sized right cheek swelling.

Role of Serine arginine protein kinase 1 and Minichromosome maintenance protein 2 in predicting epithelial ovarian cancer response to treatment and prognosis.

BACKGROUND: Serine-Arginine (SR) proteins are a conserved family of proteins involved in RNA splicing and are reported to be over-expressed in multiple cancers. The aim of the study is evaluation of the expression of Serine arginine protein kinase 1 (SRPK1) and Minichromosome maintenance protein 2 (MCM2) in epithelial ovarian cancer (EOC) and their correlation with clinicopathological features, response to therapy, progression-free survival (PFS), and cancer-specific survival (CSS). METHODS: This study was carried out on surgical specimens of 65 patients diagnosed with EOC which were submitted to immunohistochemical staining by SRPK1 and MCM2 antibodies. RESULTS: About 89.2% of cases showed SRPK1 expression and its high expression was significantly associated with type II tumors and advanced stage. All cases showed nuclear immunoreaction for MCM2 with high expression in 49.2% of cases. There was a significant relationship between high values of SRPK1 H-score and percentage of MCM2. Postmenopause, type II pathology, advanced stage, absence of complete response to the treatment, resistance to platinum-based chemotherapy, and surgery done by a general surgeon were the factors affecting PFS. Response to treatment and platinum sensitivity were the most independent factors affecting patients' PFS. The factors associated with shorter CSS were suboptimal debulking, advanced stage, absence of complete response to the treatment, platinum resistance, and high SRPK1. High SRPK1 expression and platinum sensitivity were the independent factors affecting patients' CSS. CONCLUSIONS: SRPK1 is an unfavorable biomarker in EOC patients because of its association with aggressive histologic type, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, and worse survival. SRPK1 could promote the proliferation of EOC by up-regulation of MCM2.

Immunohistochemical expression of granzyme B and perforin in discoid lupus erythematosus.

Discoid lupus erythematosus (DLE) is a chronic photosensitive dermatosis characterized by scarring and atrophy. Granzyme B is a serine protease found in the cytoplasmic granules of cytotoxic lymphocytes and natural killer cells. Perforin permits delivery of the cytotoxic granzymes A and B into target cells to induce apoptosis and cause target cell death. The current study investigated the expression of granzyme B and perforin in 25 cases of DLE and in 10 cases of normal skin by immunohistochemistry and correlated their expression with the clinicopathological features in the studied DLE group. Both granzyme B and perforin were expressed in DLE with absent expression in normal skin. They were parallelly expressed in DLE where granzyme B was associated with features of chronicity such as old age (p = 0.05) and long duration of the disease (p = 0.05). Perforin expression in DLE was associated with male gender (p = 0.04) and outdoor workers (p = 0.04). Finally, expression of both granzyme B and perforin in dermal lymphocytic inflammatory infiltrate in DLE may indicate the cytotoxicity of the infiltrate. The parallel expression of both molecules may refer to the cooperative relationship between them to enhance cytotoxicity. Higher expression of granzyme B than perforin may indicate the presence of other pathways for granzyme B release independent from perforin.