YKL-40 immunoexpression as a prognosticator of mycosis fungoides.

BACKGROUND: YKL-40 is a 40 kDa chitinase-like glycoprotein that is predicted to contribute to the pathogenesis of several inflammatory and neoplastic conditions. OBJECTIVES: To assess YKL-40 immunoexpression in different stages of mycosis fungoides (MF) to find out if YKL-40 is playing a possible role in disease pathophysiology and progression. METHODS: This work included 50 patients with different stages of MF diagnosed on the basis of clinical, histopathological, and both CD4 and CD8 immunophenotyping, in addition to 25 normal control skin. The Immune Reactive Score (IRS) of YKL-40 expression was determined in all specimens and statistically analyzed. RESULTS: YKL-40 expression reported a significant rise in MF lesions compared to control skin. Among MF specimens, the mildest expression was observed in the early patch stage followed by the plaque stage, while the strongest was in tumor stages. Positive correlations were discovered between IRS of YKL-40 expression in MF specimens and patients' age, disease chronicity, clinical staging, and TNMB classification. CONCLUSION: YKL-40 might participate in MF pathophysiology, and the highest expression is associated with advanced stages of the disease and poor outcomes. Therefore, it might be of value as a prognosticator for monitoring high-risk MF patients and follow-up assessment of treatment success.

The Value Of PD-L1 Immunohistochemical Expression In Egyptian Urinary Bladder Carcinoma Patients.

Objectives: To evaluate programmed death-ligand 1 immunohistochemical expression in the available variants of urinary bladder carcinoma, and to correlate its expression with the available clinicopathological features. Method: The retrospective study was conducted at the Faculty of Medicine, Kafrelsheikh University, Egypt, from February 2020 to April 2021, and comprised formalin-fixed and paraffin-embedded specimens of urinary bladder carcinoma belonging to patients who had no history of radiotherapy or chemotherapy. Immunohistochemicalstaining of all cases was done using anti-programmed death-ligand 1 antibody. Data was analysed using SPSS 20. RESULTS: Of the 70 specimens, 58(82.86%) had been obtained through transurethral resection of bladder tumours and 12(17.14%) through radical cystectomy. Also, 53(75.7%) specimens belonged to males and 27(24.3%) to females. The age of the cases ranged 34-83 years, and 59(84.3%) were aged ≥45 years. There were 27(38.6%) noninvasive bladder tumours and 43(61.4%) were infiltrating bladder carcinomas. Positive programmed death-ligand 1 expression was detected in 42(60%) cases. Age, gender and histopathological type were not significantly associated with the expression of programmed death-ligand 1. CONCLUSIONS: Programmed death-ligand 1 could be considered a predictive marker for aggressive bladder carcinoma and its immunohistochemical expression may aid in identifying selective patients for targeted immunotherapy.

The cardioprotective effect of human glucagon-like peptide-1 receptor agonist (semaglutide) on cisplatin-induced cardiotoxicity in rats: Targeting mitochondrial functions, dynamics, biogenesis, and redox status pathways.

The cardiotoxic effect of chemotherapeutic agents as cisplatin has become a major issue recently. Interference with mitochondrial dynamics, biogenesis, redox status, and apoptosis are the most possible underlying mechanisms. Semaglutide is a human glucagon-like peptide-1 receptor agonist (GLP-1R), which is used primarily for the treatment of DM. Various recent studies have investigated (GLP-1R) role in cardiovascular diseases due to antiapoptotic and antioxidant effects. The current study aimed to investigate the curative role of semaglutide's against cisplatin- induced cardiotoxicity and its relation to mitochondrial functions, dynamics, biogenesis, apoptosis, and redox status pathways. The study included 30 male rats divided into three groups: control, cisplatin-induced cardiotoxicity, and cisplatin-induced cardiotoxicity treated with semaglutide. At the end of the experiment heart index, serum cardiotoxicity markers, SOD, GPX activities and H2 O2 level were estimated. Mitochondrial transmembrane potential, complex I and citrate synthase enzyme activities, ATP level, Mfn2 in addition to PGC-1 α levels were assessed as biogenesis markers. Mitophagy markers PINK1 and Parkin mRNA gene expression were estimated. Histopathological examination of cardiac muscles of all studied groups and immunoassay of P53 and caspase 3 in cardiac tissue were examined to assess apoptosis. Cisplatin has disturbed mitochondrial function and dynamics, dysregulate redox status and induced mitophagy and apoptosis, in the other hand semaglutide treatment has normalized dysregulated mitochondrial function and dynamics, redox status and suppressed mitophagy and apoptosis. Semaglutide has ameliorative effect against cisplatin- induced cardiotoxicity via modulation of mitochondrial functions, dynamics, biogenesis, apoptosis, and redox status pathways.

Vitamin D3 supplementation could ameliorate the inflammatory and redox status in the muscular phase of trichinellosis.

Nutritional supplements, particularly vitamin D, have been widely used worldwide in the treatment of various infections, including parasites. This study aimed to evaluate the potential effects of vitamin D3 supplementation on the muscular phase of trichinellosis in experimental animals. Mice were divided as follows: (group I): infected untreated, (group IIa) infected and treated with vitamin D3 for 12 doses beginning 2 weeks before infection and continuing after infection, (group IIb) infected and treated with vitamin D3 for 8 doses beginning on the same day of infection, (group III) normal control, (group IVa) which received vitamin D3 for 12 doses and (group IVb) which received vitamin D3 for 8 doses. Mice were sacrificed 35 days after infection and total muscle larval count, and histopathological examination of muscle samples with immunohistochemical staining of cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) were performed. Muscle relative cathelicidin mRNA expression was assessed, as well as serum levels of muscle enzymes CK and LDH, interleukin-4 (IL-4), IL-10, IL-17 and interferon-gamma (INF-γ). Vitamin D3 supplementation significantly reduced muscle larval count, inflammatory cellular infiltration, COX2 and iNOS expression. Furthermore, it increased cathelicidin gene expression, decreased serum levels of CK and LDH and affected serum cytokine levels, increasing serum IL-4 and IL10 levels while decreasing serum INF γ and IL-17. In conclusion, vitamin D3 supplementation has favorable outcomes on the muscle phase of trichinellosis, including anti-inflammatory, antioxidant, and immunomodulatory effects.

Melatonin epigenetic potential on testicular functions and fertility profile in varicocele rat model is mediated by silent information regulator 1.

BACKGROUND AND PURPOSE: Varicocele is a leading cause of male infertility. Melatonin is a highly pleiotropic neurohormone. We aimed to characterize the melatonin epigenetic potential in varicocele and the involved molecular mechanisms. EXPERIMENTAL APPROACH: Fifty-two male albino rats were randomly divided into four groups (13 rats each): control (I), melatonin (II), varicocele (III) and melatonin treated varicocele (IV) groups. Left varicocele was induced by partial left renal vein ligation. Reproductive hormones, epididymal sperm functional parameters, testicular 3/17 ß-hydroxysteroid dehydrogenases, antioxidant enzymes, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, 8-hydroxy-2'-deoxyguanosine and histopathological/Johnsen's score were evaluated. Flow cytometry and Comet were carried out to explore extent of sperm and testicular DNA damage. Testicular expression of silent information regulator 1 (SIRT1), forkhead transcription factors-class O (type1) (FOXO1), tumour suppressor gene, P53, cation channels of sperm (CatSper) and steroidogenic acute regulatory protein was evaluated by western blot technique. Testicular expression of Bcl-2 and its associated X protein and nuclear factor kappa-light-chain-enhancer of activated B cells were assayed by immunohistochemical staining. Testicular miR-34a expression was quantified by quantitative reverse transcription-polymerase chain reaction. KEY RESULTS: The varicocele induced testicular histological injury, enhanced oxidative stress, P53-mediated apoptosis, DNA damage and increased testicular miR-34a expression paralleled with down-regulated SIRT1/FOXO axis. Melatonin treatment of varicocele rats displayed antioxidant/anti-apoptotic efficacy and improved reproductive hormones axis, CatSper expression and fertility parameters. MiR-34a/SIRT1/FOXO1 epigenetic axis integrates testicular melatonin mediated intracellular transduction cascades in varicocele. CONCLUSION AND IMPLICATIONS: Melatonin can be used as an adjuvant therapy to improve varicocele and its complication.

Unique Novel Role of Adropin in a Gastric Ulcer in a Rotenone-Induced Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease, frequently associated with a gastric ulcer. We aimed to investigate the adropin neuroprotective/gastroprotective potential in the indomethacin (IND)-induced gastric ulcer in a rotenone-induced PD model. Rats were randomly divided into four groups: normal control group, rotenone/IND treated (PD /Ulcer) group, adropin treated PD/Ulcer group, and l-dopa/omeprazole (Om) treated PD/Ulcer group. There were ten rats selected for the normal control group. Striatal dopamine (DA), apoptosis/redox status, and motor/behavioral impairments were evaluated. Gastric oxidative stress, H+/K+-ATPase activity, prostaglandin E2, mucin content, and von Willebrand factor were measured. Gastric/striatal phosphatidylinositol 3-kinase (PI3K)/phosphorylated Akt and gastric vascular endothelial growth factor (VEGF)/striatal P53 immunoreactivities were checked. Striatal P53 upregulated modulator of apoptosis (Puma)/gastric vascular endothelial growth factor receptor-2 (Vegfr-2) expressions were evaluated. Adropin successfully restored striatal DA and attenuated rotenone-induced motor/behavior deficits along with strong gastroprotective potential, possibly through antioxidant activity via reduction in malondialdehyde level and upregulated superoxide dismutase, catalase activities, and serum ferric reducing antioxidant power. Adropin restored the delicate balance between the defective pro-survival PI3K/Akt/murine double minute 2 signals and apoptotic P53/Puma pathways. Adropin can be considered as a uniquely attractive therapeutic target in PD and its associated gastric ulcer.

Significance of SOX18 expression in nonmelanoma skin cancers for prediction of high-risk patients: a preliminary study.

BACKGROUND: SOX18 is an integral transcription factor that is involved in endothelial cells differentiation during both angiogenesis and lymphangiogenesis. Therefore, it has been implicated in tumor progression and metastasis. OBJECTIVE: To study SOX18 expression in nonmelanoma skin cancers (NMSCs) in comparison to seborrheic keratosis (SK) and normal control skin, and to assess its probable role in tumor evolution and progression. PATIENTS AND METHODS: This study was conducted on 60 specimens of NMSCs: 30 basal cell carcinomas (BCC) and 30 squamous cell carcinomas (SCC), 30 specimens of SK, and 30 normal skin specimens. All were examined for immunohistochemical expression of SOX18 antibody. Additionally, morphometric assessment of vessel density (blood & lymphatic) in each specimen was estimated. RESULTS: Significant SOX18 overexpression was observed in all studied cutaneous tumors in comparison to control skin. The highest score of SOX18 expression was detected in SCC, then BCC, and the least expression was reported in SK with significant difference between them. Furthermore, significant upregulation of SOX18 expression was observed in high-risk types of both BCC and SCC compared to low-risk types. Stromal vessel density showed significant differences between the studied tumors with the highest mean value in SCC, followed by BCC and then SK. Positive correlation between SOX18 expression in the studied tumors and their vessel density was detected. CONCLUSIONS: SOX18 may have a potential role in the evolution as well as progression of NMSCs, possibly through induction of both angiogenesis and lymphangiogenesis. Furthermore, it could be beneficial for prediction of NMSC patients with poor prognosis.

Significance of Expression of Cancer Stem Cell Markers CD133 and Nestin in Pancreatic Intraepithelial Carcinoma-invasive Adenocarcinoma Sequence.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and one of the most leading causes of cancer related deaths. It has a very poor prognosis with high recurrence rate. We investigated the expression of CSC markers (CD133 and nestin) in 100 patients [30 pancreatic intraepithelial tumor cases (PanIN) and 70 PDAC cases] and correlate the expression levels of these markers with clinicopathological data with the aid of Ki67 expression. Our findings showed that both cancer stem markers are related to the grade, stage, metastasis of PDAC and to the grade of PanIN cases and revealed that both markers are associated with PanIN-PDAC sequence with inverse relation between them. Both markers may contribute to proliferation, differentiation, invasiveness, and histologic types of PDAC. Sothey may also be useful for developing new therapeutic modalities for PDAC.

The Prognostic Value of Podoplanin Expression in Nonmelanoma Skin Cancers: Correlation With Lymphatic Vessel Density.

BACKGROUND: Podoplanin is one of the integral molecules controlling cellular motility and migration that is considered crucial in initiating tumor invasiveness and metastasis. OBJECTIVE: This work aimed at studying the immunohistochemical expression of podoplanin in nonmelanoma skin cancers (NMSCs) and seborrheic keratosis (SK) in comparison to normal control skin and to evaluate its possible role in their pathogenesis. PATIENTS AND METHODS: This study included 120 patients and paraffin blocks of epidermal tumors [30 SK, 30 basal cell carcinoma (BCC), 30 basosquamous carcinoma (BSC) and 30 squamous cell carcinoma (SCC)], in addition to 30 normal control skin specimens from age- and sex-matched healthy volunteers. All were examined for intratumoral and peritumoral immunohistochemical expression of podoplanin antibody (D2-40). In addition, morphometric measurement of lymphatic vessel density was evaluated in all studied specimens. RESULTS: Podoplanin expression was significantly upregulated in all the studied epidermal tumor specimens in comparison to normal control skin specimens. The highest mean value of podoplanin expression (both intratumoral and peritumoral cells) was observed in SCC followed by BSC, then BCC, SK, and control skin in the same sequence. Positive correlations were detected between its expression in both BSC and SCC with the mean of lymphatic vessel density in the studied specimens and the presence of lymph node metastasis. CONCLUSIONS: Podoplanin plays an evident role in the development and progression of both benign and malignant skin neoplasms and may serve as a potential predictor of their clinical course and prognosis.

Assessment of the potential therapeutic effects of omeprazole in Schistosoma mansoni infected mice.

Schistosomiasis is a neglected chronic parasitic disease with a significant lasting morbidity. Currently, praziquantel (PZQ) is the most efficient drug for schistosomiasis worldwide. However, the possibility of the occurrence of resistance to PZQ is increasing. Therefore, there is a vital need to find new antischistosomal drugs or to increase the efficacy of the existing ones. Omeprazole is a proton pump inhibitor which is reported to have antiparasitic properties. Thus, the aim of this study was to assess the potential therapeutic effects of omeprazole in experimental Schistosoma mansoni infection either alone or in combination with PZQ. For this aim, 80 laboratory bred mice were divided into 3 groups; uninfected control, infected untreated control, and infected and treated at tenth week P.I. The last group was divided into three subgroups that received either PZQ alone, omeprazole alone, or both drugs. The effectiveness of treatment was assessed by adult worm counts, liver egg count, scanning electron microscopy of adult worms, histopathological, and immunohistochemical (GFAP) examination. There was significant reduction of adult worm counts, liver egg counts, size, diameter of hepatic granulomas, hepatic fibrosis, and GFAP expression in the group that received combined treatment as compared to PZQ group. Moreover, the tegumental changes were more evident in the group that received combined treatment. In conclusion, the administration of omeprazole with PZQ improved the efficacy of PZQ in the treatment of Schistosomiasis mansoni.

Ameliorative effects of autophagy inducer, simvastatin on alcohol-induced liver disease in a rat model.

Alcoholic liver disease (ALD) encompasses a variety of liver injuries with various underlying mechanisms but still no effective treatment. So we aimed to monitor the influence of simvastatin on alcohol-induced liver injury and elucidate the underlying mechanisms of its cytoprotective effect. Thirty male albino rats were randomly divided into five equal groups. Group 1 (control): received a standard diet; group 2: received simvastatin (10 mg kg-1 day -1 ) once a day orally for 8 weeks; group 3: received 20% ethanol (7.9 g kg -1 day -1 ) daily orally for 8 weeks; group 4: received 20% ethanol along with same simvastatin dose daily for 8 weeks; group 5: received 20% ethanol orally for 8 weeks then received the same simvastatin dose for the next 8 weeks. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. Liver tissue malondialdehyde, reduced glutathione levels, and superoxide dismutase activity were estimated. B-cell lymphoma 2 and C/EBP homologous protein levels were evaluated by enzyme linked immunosorbent assay (ELISA). Light chain 3-II and peroxisome proliferation-activated receptor gamma messenger RNA expression was assessed by real-time polymerase chain reaction. Immunohistochemical staining was performed using anti-rat tumor necrosis factor-alpha antibody. Our results revealed that simvastatin treatment was able to ameliorate alcohol-induced liver damage; the improved biochemical data were confirmed by histopathological evaluation. Simvastatin being an autophagy inducer was able to prevent and reverse alcohol-induced liver changes via induction of autophagy, attenuation of oxidative stress, inflammation, and endoplasmic reticulum stress-induced apoptosis. Therefore, our findings suggest that treatment with simvastatin may be a useful approach in the management strategy of ALD.

Prostatic Carcinogenesis: More Insights.

BACKGROUND: Prostatic carcinoma ranks as the second most common malignant tumor and the fifth cause of cancer-related deaths in men. Many studies now focus on the different molecules involved in prostatic carcinogenesis. Maspin and prohibitin (PHB) are suggested to play crucial roles in the development and progression of many cancers; however, their roles in prostatic carcinogenesis have not been fully elucidated. AIM: This work was designed to study the immunohistochemical expression of maspin and PHB in prostatic carcinoma in comparison to their expression in benign prostatic hyperplasia (BPH) to give more insights about their roles in prostatic carcinogenesis. MATERIALS AND METHODS: Archival blocks of 30 cases of prostatic adenocarcinomas and 15 cases of BPH were subjected to histopathological examination and immunohistochemical evaluation of maspin and PHB expression. RESULTS: Maspin showed higher expression in prostatic carcinoma (88.9% of cases) compared to BPH (20% of cases). PHB expression was detected only in prostatic carcinoma (84.4% of cases), while all cases of BPH were negative. The expression of both maspin and PHB showed statistically significant increase with increasing Gleason score (P = 0.0125 and 0.0065 respectively). CONCLUSIONS: Overexpression of maspin and PHB in prostatic carcinoma reflects their vital roles in prostatic carcinogenesis. Their upregulation with increasing Gleason score indicates their prognostic significance. Moreover, PHB may differentiate between prostatic carcinoma and BPH being expressed only by malignant cells.

Glucose transporter-1 (GLUT-1) expression in psoriasis: correlation with disease severity.

BACKGROUND: Epidermal hyperproliferation with abnormal differentiation, inflammation, and angiogenesis are the key features of psoriasis. Glucose transporter-1 (GLUT-1) is a member of facilitative sugar transporters that are integral membrane glycoproteins moving sugar across cell membrane. OBJECTIVE: The objective of this study was to study the GLUT-1 expression in psoriasis. PATIENTS AND METHODS: Forty patients with psoriasis vulgaris and 20 healthy individuals were included in the study. Skin biopsies were taken from lesional and nonlesional skin of psoriasis patients as well as normal skin of control subjects. All were examined for GLUT-1 antibody expression by immunohistochemistry and GLUT-1 mRNA expression by real-time polymerase chain reaction (RT-PCR). In addition, specimens of psoriasis lesions were stained by hematoxylin and eosin and CD31 for morphometric analysis of histopathological parameters. RESULTS: The intensity of GLUT-1 immunohistochemical expression and the relative levels of GLUT-1 mRNA expression in psoriasis lesions were upregulated in lesional skin of psoriasis patients in comparison with their nonlesional skin as well as normal control skin. GLUT-1 expression in psoriasis lesions showed significant positive correlations with Psoriasis Area and Severity Index (PASI) score, mean of epidermal thickness, inflammatory cell density, and microvessel density. CONCLUSION: Glucose transporter-1 could play a role not only in the onset of psoriasis but also in the progression and severity of the disease. It may participate in the pathogenesis of psoriasis through the facilitation of epidermal hyperproliferation, inflammation, and angiogenesis.

Napsin-A, a Possible Diagnostic Marker for Differentiating Clear Cell Ovarian Carcinoma From Other High-grade Ovarian Carcinomas.

Ovarian clear cell carcinoma (CCC) is divergent from other types of epithelial ovarian carcinoma in terms of clinicopathologic and molecular features. It should be separated from other high-grade carcinomas of the ovary for appropriate treatment. Napsin A is a reliable marker for adenocarcinoma of the lungs, but its role in ovarian epithelial carcinomas is vague. We investigated the expression of a panel of TTF-1, paired box 8, estrogen receptor, Wilms tumor 1, and Napsin A in 100 cases of high-grade ovarian carcinomas. All the examined cases were TTF-1 negative and paired box 8 positive. The 2 biomarkers estrogen receptor together with Wilms tumor 1 can separate CCC from endometriod carcinoma, yet this cannot be carried out in the case of serous and mucinous carcinomas of high grade. Napsin A can differentiate CCC with high sensitivity and specificity. It can be concluded that Napsin A is a sensitive and specific marker for CCC of the ovary. However, an entire marker panel may be useful for distinguishing ovarian CCC from other mimics.

Role of inducible nitric oxide synthase and interleukin-6 expression in estimation of skin burn age and vitality.

Estimation of age and vitality of burn injury both in the living and dead is essential in forensic practice. Nitric oxide and interleukin-6 (IL-6) play an important role in skin burn healing. In this study, the expression of inducible nitric oxide synthase (iNOS) and IL-6 proteins during skin burn healing in rats was studied for purposes of burn dating and to differentiate between ante-mortem and post-mortem burn. Ante-mortem skin burns were created on forty five rats. Normal and burnt skin samples were taken at 1, 3, 5, 7, 9, 11, 13, 15 and 21 days following burn induction (5 rats for each stage). Post-mortem burn was inflicted 6 h after scarification in another five rats. There was a statistically significant difference in both iNOS and IL-6 expression between the different time intervals of the ante-mortem burn. Expression of both iNOS and IL-6 decreased remarkably in the post-mortem burn with a statistically significant difference from ante-mortem intervals. A statistically significant positive association between the two markers was found. These results indicate that both iNOS and IL-6 expression in ante-mortem burnt skin was time dependent and significantly differed from post-mortem burn. Further research on humans is recommended.

Diagnostic utility of vimentin, CD117, cytokeratin-7 and caveolin-1 in differentiation between clear cell renal cell carcinoma, chromophobe renal cell carcinoma and oncocytoma.

Overlapping morphological characteristics pose some difficulties in making a proper diagnosis of clear cell renal cell carcinoma (CCRCC), chromophobe renal cell carcinoma (ChRCC), and oncocytoma, on the basis of hematoxylin-eosin-stained tissue sections. Our objective was to find out a fast, reliable panel of immunohistochemical markers for differentiation between them. The study was carried out on 55 selected renal tumor specimens: 36 cases of CCRCC, seven cases of ChRCC, and 12 cases of oncocytoma. The specimens were stained immunohistochemically for vimentin, CD117, cytokeratin (CK)7, and caveolin (Cav)-1. Sensitivity and specificity for each marker were calculated. Vimentin expression was exclusively observed in CCRCC (100%) and negative in ChRCC and oncocytoma. CD117 was absent in CCRCC, but it was strongly expressed in ChRCC (85.5%) and oncocytoma (91.7%), with high sensitivity and specificity. Most CCRCCs and oncocytomas were negative for CK7 (91.7% and 83.3%, respectively), in contrast to ChRCCs, which showed positivity in nearly 86% of the cases. Good sensitivity and specificity were calculated for CK7 in differentiating studied oncocytic tumors. Cav-1 was positive in ~78% of the CCRCCs and in all ChRCCs, whereas the vast majority of oncocytomas were negative. So the immunoprofile of CCRCC was vimentin+/CD117-/CK7-/Cav-1±, ChRCC was vimentin-/CD117+/CK7+/Cav-1+, and oncocytoma was vimentin-/CD117+/CK7±/Cav-1-. So, by using combination of four markers (vimentin, CD117, CK7, and Cav-1), we achieved excellent sensitivity and specificity for differential diagnosis of CCRCC, ChRCC and oncocytoma.

Do HOXB13 and P63 have a role in differentiating poorly differentiated prostatic carcinoma from urothelial high-grade carcinoma?

Poorly differentiated prostatic carcinoma may overlap with high-grade urothelial carcinoma; a distinction is a must as treatments differ. This study aims to evaluate traditional (PSA and HMWCK) and relatively novel (P63 and HOXB13) markers in distinguishing them; and to evaluate their role in the diagnosis of challenging cases. Sections from: diagnosed group includes 65 prostatic and urothelial carcinoma cases were stained with PSA, HMWCK, P63, and HOXB13. Sensitivity, specificity, and accuracy were evaluated. The second group includes 25 challenging cases which were stained first by PSA and HMWCK, then solved the problematic cases with P63 and HOXB13. PSA and HMWCK were sensitive and specific for prostatic and urothelial carcinomas, respectively, but the sensitivity and accuracy were higher for P63 and HOXB13. By using the traditional markers, 17 cases were diagnosed in the second group while the remaining eight cases need the novel markers to be diagnosed. A confident diagnosis can be established in the majority of cases of poorly differentiated carcinoma in either prostatic or urothelial by using a panel of PSA and HMWCK. In some problematic cases, an extended panel including P63 and HOXB13 is helpful in resolving the diagnosis.

Immunohistochemical Panel for Differentiating Renal Cell Carcinoma with Clear and Papillary Features.

Renal cell carcinoma (RCC) in which clear cells with papillary architecture are present is a difficult diagnostic challenge. The most common type, clear cell RCC, only rarely has papillary architecture. The second most common one, papillary RCC, only rarely contains clear cells. However, two recently described less-common types, clear cell papillary and Xp11 translocation RCC characteristically feature both papillary architecture and cells with clear cytoplasm. Accurate diagnosis has both prognostic and therapeutic implications. This study aims to highlight the helpful cytomorphologic and immunohistochemical features of each of these entities to enable reproducible classification. Sixty RCC cases with clear cells and papillary architecture were selected and classified according to The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia and graded according to The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma then stained for CK7, carbonic anhydrase IX (CA IX), α-methylacyl-CoA-racemase (AMACR) and TFE-3. The characteristic immunoprofile of Clear RCC is CK7-, AMACR-, CA IX+ and TFE3-, papillary RCC is CK7+, AMACR+, CAIX- and TFE3-, while for clear cell papillary RCC it is CK7+, AMACR-, CAIX+ and TFE3- and lastly Xp11translocation RCC is CK7-, AMACR+, CAIX- and TFE3+. Immunohistochemical staining for CA IX, CK7, AMACR and TFE3 comprises a concise panel for distinguishing RCC with papillary and clear pattern.

Immunohistochemical panel for differentiating renal cell carcinoma with clear and papillary features.

OBJECTIVES: Renal cell carcinoma (RCC) in which clear cells with papillary architecture are present is a difficult diagnostic challenge. Clear cell RCC, rarely has papillary architecture. Papillary RCC rarely contains clear cells. However, two recently described types; clear cell papillary and Xp11 translocation RCC characteristically feature both papillary and clear cells. Accurate diagnosis has both prognostic and therapeutic implications. This study aims to highlight the helpful features of each of these entities to enable reproducible classification. METHODS: Sixty RCC cases with clear cells and papillary architecture were selected and classified according to The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia and graded according to The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma then stained for CK7, carbonic anhydrase IX (CA IX), α-methylacyl-CoA-racemase (AMACR) and TFE-3. RESULTS: The characteristic immunoprofile of Clear RCC is CK7-, AMACR-, CA IX+ and TFE3-, papillary RCC is CK7+, AMACR+, CAIX- and TFE3-, while for clear cell papillary RCC it is CK7+, AMACR-, CAIX+ and TFE3- and lastly Xp11 translocation RCC is CK7-, AMACR+, CAIX- and TFE3+. CONCLUSIONS: Staining for CA IX, CK7, AMACR and TFE3 comprises a concise panel for distinguishing RCC with papillary and clear pattern.

Evaluation of p16, human papillomavirus capsid protein L1 and Ki-67 in cervical intraepithelial lesions: potential utility in diagnosis and prognosis.

Cervical dysplasia, a potentially precancerous lesion, has increased in young women. Detection of cervical dysplasia is important for reducing morbidity and mortality in cervical cancer. This study analyzes the immunohistochemical expression of p16, HPV L1 capsid protein and Ki-67 in cervical intraepithelial lesions, and correlates them with lesion grade to develop a set of markers for diagnosis and detect the prognosis of cervical cancer precursors. Seventy-five specimens were analyzed, including 15 cases of CIN 1, 28 cases of CIN 2, 20 cases of CIN 3, and 12 cervical squamous carcinomas, besides 10 normal cervical tissues. They were stained for p16, HPV L1 and Ki-67. Sensitivity, specificity, predictive values and accuracy were evaluated for each marker. p16 expression increased during progression from CIN 1 to carcinoma. HPV L1 positivity was detected in CIN 2 and decreased gradually as the CIN grade increased but disappeared in carcinoma. Strong Ki-67 expression was observed in high grades CIN and carcinoma. p16, HPV L1 and Ki-67 were sensitive but with variable specificity in detecting CIN lesions. p16, HPV L1 and Ki-67 are useful markers in establishing the risk of high-grade CIN. They complete each other to reach an accurate diagnosis and to detect the prognosis.