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.

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.

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.

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.

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.

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.

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.

Utility of immunohistochemical markers in diagnosis of follicular cell derived thyroid lesions.

Differentiating the follicular derived lesions can be challenging. Although immunohistochemistry is generally accepted as a useful ancillary technique in the diagnosis, controversy exists regarding the best marker or combination of markers to distinguish each lesion from its mimics. In this study, we aimed at evaluating multiple markers to compare their sensitivity and usefulness, and to find out if a combination of the evaluated markers can be of additional value in discriminating thyroid lesions. The study included two groups of follicular derived thyroid lesions; benign group (Grave's disease, nodular goiter, Hashimoto's and adenoma) and malignant group (papillary, follicular carcinoma, well differentiated tumors of unknown malignant potential and follicular tumour of unknown malignant potential). Immunohistochemical evaluation of CD56, HBME-1, Gaectin-3 and CK19 were done. The sensitivity, specificity for each marker and their combination were calculated. Each marker was sensitive and specific for certain lesion but the sensitivity and specificity was increased when use combination of markers. Although no single marker is completely sensitive and specific for follicular thyroid lesions, the combination of CD56, HBME-1, Gaectin-3 and CK19 attains high sensitivity and specificity in diagnosis.

Differential caveolin-1 expression in colon carcinoma and its relation to E-cadherin-ß-catenin complex.

BACKGROUND: Colorectal cancer is the third common cancer and the second leading cause of cancer-related death in the Western world. Caveolin-1 is a new emerging prognostic marker and has different expression abilities in different cancers. The expression of caveolin-1 in colon carcinogenesis is still confusing. E-cadherin and ß-catenin have a definite role in invasion and progression. Our study is designed to explore the role of caveolin-1 in cancer colon carcinogenesis and tries to elucidate the relation between its expression and E-cadherin and ß-catenin expression in colon cancer. MATERIALS AND METHODS: A total of 70 formalin-fixed, paraffin-embedded colon carcinoma specimens were studied for the expression of the 3 proteins, and a correlative study was done between each protein and different clinicopathologic parameters and between the 3 markers. RESULTS: As the tumor becomes more aggressive and invasive and as it metastasizes, it losses the stromal caveolin-1 and E-cadherin and gains the cellular caveolin-1 and the abnormal ß-catenin expression. Also, there were parallel changes between stromal caveolin-1 and E-cadherin on one side and between the cellular caveolin-1 and ß-catenin on another side. CONCLUSIONS: Our findings link caveolin-1 to the power of infiltration and spread, aggressiveness, and differentiation of cancer colon, and this may be happen through E-cadherin-ß-catenin complex.

Prevalence of androgen receptors in invasive breast carcinoma and its relation with estrogen receptor, progesterone receptor and Her2/neu expression.

BACKGROUND AND AIMS: Although Breast carcinoma had many targeted biomarkers for its treatment, however, it is a heterogeneous disease with different outcomes and need new markers especially for the triple negative group when estrogen receptor, progesterone receptors and Her2/neu are negative. Androgen receptor is a new target with unclear role. The aim of this study was to examine the prevalence of androgen receptors in invasive breast cancer and tries to elucidate its relation to some well recognized clinicopathological and immunohistochemical markers. MATERIALS AND METHODS: One hundred and fifty cases of invasive breast carcinoma were evaluated for type, grade and stage and studied immunohistochemically for estrogen receptor, progesterone receptor, Her2/neu and androgen expression. Androgen receptor expression was correlated with histopathological factors and the three studied markers separately then the studied cases were classified into three groups according to estrogen, progesterone receptor and Her2/neu expression and correlated with androgen receptor expression. RESULTS: Androgen receptor was expressed in 71% of breast cancer cases. Its expression is associated significantly with both the stage and the grade. Also it was significantly associated with estrogen receptor and Her2/neu expression. It was expressed in a significant number of triple negative breast carcinoma, in Her2/neu positive cases and in estrogen negative cases which indicate that androgen receptor could be a new target for the treatment of these groups. CONCLUSIONS: Although the impact of androgen receptor on breast cancer outcomes had not been clearly established, this result may provide evidence that androgen receptor is a good prognostic and predictive marker.

Immunophenotyping of dendritic cells in lesional, perilesional and distant skin of chronic plaque psoriasis.

Psoriasis affects 2.7% of the world's population. The sequence of these events remains controversial. Because antigen presenting is necessary for T-cell activation, dendritic cells may be involved in the pathogenesis of psoriasis. To investigate their role, we examined immunophenotyping of different dendritic cells and their distribution and numbers in psoriasis patients. Immunohistochemistry of CD1a, CD11c, CD86 and BDCA2 were performed using paraffin-embedded tissue obtained from a total of 45 patients with psoriasis. Samples were taken from the lesion, perilesional and distant skin and normal skin obtained from 10 control cases. There were marked increase in the number of positive CD1a, CD11c, CD86 and BDCA2 cells in perilesional and the psoriatic skin when compared to the distant skin and they were the least in the normal control skin. So different dendritic cells subsets have a very important role in psoriasis pathogenesis especially in initiation of the plaque in the perilesional skin.

Immunohistochemical expression of epidermal growth factor receptor, E-cadherin, and matrix metalloproteinase-9 in ovarian epithelial cancer and relation to patient deaths.

Ovarian cancer is the most frequent cause of death from gynecologic cancer in the world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR), E-cadherin, and matrix metalloproteinase (MMP)-9 are frequently studied in cancer; but their prognostic value in ovarian carcinoma remains unclear. In this study, we investigated the immunohistochemical expression of EGFR, E-cadherin, and MMP-9 in 120 cases of ovarian epithelial carcinoma; their relation to each other; their relation to histologic type, grade, and stage; and their relation to death rates after 3years of follow-up. Our results show that EGFR and MMP-9 were overexpressed extensively in high grades and advanced stages especially in nonserous carcinomas. E-cadherin was gradually lost in advanced cancers. There was a positive relation between the 3 antibodies and between them and the death rates. There is a strong relationship between EGFR and MMP-9, and this relation may occur by affecting E-cadherin. The present study provides a rationale for evaluating drugs that target these new pathways that may be promising in ovarian cancer treatment.

Prognostic significance of vascular endothelial growth factor, basic fibroblastic growth factor, and microvessel density and their relation to cell proliferation in B-cell non-Hodgkin's lymphoma.

Vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (b-FGF) have been described as essential cytokines in the regulation of angiogenesis. Their elevation has been associated with an unfavorable outcome in different neoplasms. However, their role in angiogenesis and proliferation in B-cell non-Hodgkin's lymphoma (B-NHL) is unclear. Seventy cases of B-NHL besides 5 cases with reactive lymphadenitis were collected randomly and classified according to World Health Organization classification, Ann Arbor staging. They were subjected to immunostaining using VEGF, b-FGF, CD34, and Ki67 markers. There were a positive correlation between the proliferation and aggressiveness of the tumor as measured with Ki67 and both VEGF and b-FGF, and this was reflected on the stromal increase in microvessel density as measured by CD34. In conclusion, as the tumor becomes more aggressive, it also becomes independent of stromal paracrine factors by the establishment of an autocrine VEGF and b-FGF stimulation that can increase its angiogenesis and proliferation.