To apply the immunohistochemical method using robust biomarkers; Gli1 & β catenin trying to i... more To apply the immunohistochemical method using robust biomarkers; Gli1 & β catenin trying to identify sonic hedgehog (SHH) & Wingless (WNT) active tumors. Also identification of the molecular subgroups of medulloblastoma has immediate clinical relevance guiding therapeutic stratification and the use of targeted therapies. This retrospective study was conducted on 49 tissue specimens of medulloblastoma cases for evaluation of immunohistochemical (IHC) expression of GLi1 and β-catenin. The studied cases showed absence of nuclear positivity of β catenin & 15/49 cases (30.6%) exhibited an activated sonic hedgehog signaling pathway (SHH) pronounced by nuclear positivity for Gli1. 34/49 cases (69.4%) cases that showed absence of nuclear reactivity for Gli1 and β catenin were considered as non SHH/WNT medulloblastoma group. There were no statistical significant differences between the 2 subgroups as regards to the clinical and histopathological features. Non SHH/WNT pathway identified via the absence of nuclear localization to either Gli1 & β catenin represents a major contributor to medulloblastoma in the studied Egyptian patients.
Skin tags (STs) are common benign dermal connective tissue neoplasms that are mainly composed of ... more Skin tags (STs) are common benign dermal connective tissue neoplasms that are mainly composed of loose fibrous tissue. However, their exact etiology is not fully understood. Leptin is a major player in the biology and pathology of the skin and its appendages. It is linked to cell differentiation, proliferation, migration, and survival with pronounced effects on angiogenesis, blood flow, and tissue perfusion. This study aimed at investigating the possible role of leptin in STs pathogenesis and correlating its expression with different clinical and histopathological parameters. Using immunohistochemical techniques, we examined 90 subjects. These included 60 non-obese cases with STs and 30 age-, gender- and Body Mass Index-matched normal subjects as a control group. Leptin was overexpressed in STs compared with normal skin (p < .001). Nuclear and nucleocytoplasmic patterns were significantly associated with cases both in epidermis (p < .04) and dermis (p < .001). Higher epider...
Carbonic anhydrase IX (CAIX) is an enzyme whose expression is very limited in normal tissues and ... more 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.
Analytical and quantitative cytopathology and histopathology, 2014
To elucidate the role of toll-like receptor 2 (TLR2) in the pathogenesis of acne vulgaris through... more To elucidate the role of toll-like receptor 2 (TLR2) in the pathogenesis of acne vulgaris through its immunohistochemical localization in inflammatory and noninflammatory lesions of this disease entity. Using standard immunohistochemical techniques, we examined 30 acne cases (involved and noninvolved skin) and the normal skin biopsies of 30 sex- and age-matched, healthy subjects representing the control group. All examined cases showed positive TLR2 expression in epidermis, pilosebaceous units and dermal inflammatory infiltrate. There were statistically significant differences between acne-involved skin and normal skin and between acne-involved and noninvolved skin regarding TLR2 expression intensity in pilosebaceous units (p < 0.001 for both) and dermal inflammatory infiltrate (p < 0.001 for both). Intense TLR2 expression was in favor of inflammatory acne lesions in pilosebaceous units (p = 0.03) and dermal inflammatory infiltrate (p < 0.05). Intense TLR2 expression was al...
Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of caveolae, sphing... more Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of caveolae, sphingolipid and cholesterol-rich invaginations of the plasma membrane involved in vesicular trafficking and signal transduction. Over the recent years there has been controversy about their role in breast cancer and their suitability as markers of basal-like phenotype. Caveolin-1 and CAV2 protein expression was assessed on a tissue microarray containing 880 unselected invasive breast cancer cases, by means of immunohistochemistry. Caveolin-1 and CAV2 expression was observed in 13.4 and 5.9% of all breast cancer, respectively. Their expression was strongly associated with high histological grade, lack of steroid hormone receptor positivity (ER and PR), and expression of basal markers (basal cytokeratins, P63, P-cadherin). Furthermore, there was a significant association between CAV1 and CAV2 expression and basal-like phenotype. On univariate analysis only CAV2 had a prognostic impact on breast...
Journal of the Egyptian National Cancer Institute, 2006
Cyclooxygenase-2 (Cox-2) is the inducible form of cyclooxygenase enzyme. Cox-2 is induced in nume... more Cyclooxygenase-2 (Cox-2) is the inducible form of cyclooxygenase enzyme. Cox-2 is induced in numerous processes such as cellular growth, differentiation, inflammation and tumorogenesis. Assessment of Cox-2 expression in chronic gastritis and gastric carcinoma. Sixteen chronic gastritis (CG) and 43 gastric carcinoma cases were subjected to an immunohistochemical approach using anti Cox-2 antibody. All CG cases displayed positive epithelial Cox-2 expression with only 25% positivity for stromal expression. Eighty six percent of gastric carcinoma showed epithelial Cox-2 expression that was significantly correlated with lymph node involvement (p<0.01), advanced stage (p=0.01), high microvessel density (MVD) (p=0.0001), vascular invasion (p=0.002), perineural invasion (p=0.01) and low apoptotic count (p<0.0001). Stromal Cox-2 expression was seen in 79% of gastric carcinoma cases and was significantly associated with low apoptotic count (p=0.0007), vascular invasion (p=0.001) and hig...
Trichoepithelioma (TE) is a benign tumor of follicular origin that presents as small, skin-colore... more Trichoepithelioma (TE) is a benign tumor of follicular origin that presents as small, skin-colored papules predominantly on the face. When more than one family member is affected, the disease is known as multiple familial trichoepithelioma (MFT). It is a rare autosomal dominant (AD) skin disease. Malignant transformation is very rare. We present a case of MFT in a female patient and her father with malignant transformation to basal cell carcinoma (BCC) in the father. We summarized the main histological differential parameters between TE and BCC and applied immunophenotyping for both by administration of Bcl2, CD34, CD10 and androgen receptor (AR) antibodies.
Parachordoma is an extremely rare soft tissue tumor of unknown lineage. Parachordoma develops mos... more Parachordoma is an extremely rare soft tissue tumor of unknown lineage. Parachordoma develops most often on the extremities. Only 2 cases have been reported as pelvic parachordoma. A 46-year old Egyptian woman with a huge painful pelvic mass was found to have a parachordoma with ectopic pelvic right kidney. There is only one report in the literature of fine needle aspiration cytology in this setting. The microscopic picture of parachordoma is not new to pathologists but the gross picture of this rare tumor has not previously been published; not even in the World Health Organization classification of soft tissues tumors. Diagnosis was confirmed by immunohistochemistry. The patient is in good clinical condition without any evidence of recurrence or metastasis after 84 months of follow up.
The immunohistochemical (IHC) subtyping of breast cancer can be a useful substitute for gene expr... more The immunohistochemical (IHC) subtyping of breast cancer can be a useful substitute for gene expression analysis. The aim of this study was to investigate the relationship of CK8/18 to the biology of breast carcinoma (BC) represented by its IHC subtypes. The IHC expression of CK8/18 was correlated with IHC subtypes of BC using ER, PR, HER2/neu, and Ki67 LI (with cutoff 14%). All cases showed CK 8/18 expression in tumour cells with varying degree of intensities; 49/70 cases (70%) showed diffuse cytoplasmic expression (loss of membranous pattern), while 21/70 cases (30%) showed membrano-cytoplasmic pattern. Adjacent non-neoplastic breast lobules showed membrano-cytoplasmic pattern in 58% of cases, which was significantly different from the pattern in invasive cancer (P = 0.002). A loss of membranous pattern in malignant tumours was significantly associated with higher tumour grade (P = 0.02), higher mitotic count (P = 0.03), and negative HER2/neu status (P = 0.04). CK 8/18 H score ran...
Background: Lipoid proteinosis (Urbach-Wiethe disease) is a rare progressive autosomal recessive ... more Background: Lipoid proteinosis (Urbach-Wiethe disease) is a rare progressive autosomal recessive disorder, characterized histologically by deposition of periodic acid Schiff-positive, diastase resistant, hyaline-like material into the skin, upper aerodigestive tract, and internal organs.
Kaposi sarcoma (KS) is a neoplasm of the endothelial cells. It often manifests with multiple vasc... more Kaposi sarcoma (KS) is a neoplasm of the endothelial cells. It often manifests with multiple vascular nodules on the skin and other organs. It is a systemic, malignant and multifactorial disease and has a variable course. There are four types: classic, endemic, iatrogenic and HIV-associated. The primary presentation on the penis and face is uncommon and is mainly observed in HIV-positive patients. Multiple treatment modalities are used including surgery, cryotherapy, electrosurgery, laser and radiation therapy.
Wilms tumor is a mixed embroynal neoplasm of the kidney . HER2 is an onco-protein. Its over-expre... more Wilms tumor is a mixed embroynal neoplasm of the kidney . HER2 is an onco-protein. Its over-expression could be implicated in the development of many tumors. The clinico-demographic and pathological data of 28 Wilms tumor patients were , reviewed. The tissue samples were examined by light Microscopy then immunohistochemical staining for HER2/neu expression. Additional 28 normal surrounding renal tissue specimens were included. There was significant differences between HER2/neu positive and HER2/neu negative Wilms tumors in relation to stage, histological phase and epithelial differentiation (P>0.05 for all). The overall survival advantage was noticed if Wilms tumor was at early stages (I and II) (Log-rank=13.23 and P>0.001), homologous epithelial differentiation (Log-rank=6.01 and P=0.04), as well as HER2/neu positive tumors (Log-rank=6.14 and P=0.013). A statistical significant trend toward a longer recurrence free survival was, noticed if Wilms tumor was at early stages (Log-rank=21.22, P>0.0000) and if HER2/neu positive (Log-rank=8.53, P=0.004). HER2/neu expression in Wilms tumor could be a marker for epithelial and homologous differentiation and its expression could be a good predictor for overall survival and longer recurrence free survival.
Ephrin A4 is one of the ephrin ligand molecules belonging to the tyrosine kinases receptor family... more Ephrin A4 is one of the ephrin ligand molecules belonging to the tyrosine kinases receptor family. It was originally identified in a T-lymphoma cell line and seen to be expressed in human adult tissue as well as several tumor types. In our previous study, we showed the unique pattern of ephrin A4 immunohistochemical staining, which differed according to the type of examined bone specimens (normal bone, primary, and metastatic osteosarcoma lesions). The aim of the present study is to evaluate the prognostic impact of ephrin A4 expression in a group of primary osteosarcoma patients. Ephrin A4 immunohistochemical expression was carried out on 47 primary osteosarcoma cases. Ephrin A4 was expressed in 82.9% of osteosarcoma cases with cytoplasmic localization in 58.9% of positive cases. The cytoplasmic pattern was significantly associated with aggressive histopathological types of osteosarcoma (P = 0.02), advanced stage (P = 0.04), the presence of metastasis (P = 0.03), inferior response to neoadjuvent chemotherapy (P = 0.04), and tended to be associated with a shorter event-free survival (P = 0.09). The cytoplasmic pattern of ephrin A4 could identify a subgroup of primary osteosarcoma patients with a high liability for progression, poor prognosis, and inferior response to chemotherapy.
Multiple theories were described concerning the pathogenesis of orbital infection in rhinosinusit... more Multiple theories were described concerning the pathogenesis of orbital infection in rhinosinusitis, but no theory was proved. Understanding the cause of complication can allow its proper management. We speculate that subperiosteal orbital abscess (SPOA) secondary to rhinosinusitis is similar to subperiosteal abscess associated with osteomyelitis of bone all over the body. The objective was to evaluate bony changes of the ethmoidal sinuses in complicated rhinosinusitis patients with SPOA. This prospective controlled study was performed on eight patients undergoing endoscopic sinus surgery drainage for rhinosinusitis complicated with SPOA. Age, radiographic bony characteristics, and histopathological Wndings were all documented. Ethmoidal bone specimens were examined and assessed histopathologically. Purulence of SPOA was collected and sent for cultures. The authors evaluated normal ethmoidal bone specimens taken endoscopically from the medial wall of obstructing concha bullosa in ten control patients. The analysis revealed CT and histopathologic changes consistent with high grades of ethmoidal bone pyogenic osteitic changes. Coagulase-positive staphylococci were the predominant cultured bacteria (62.5%) in SPOA. These Wndings suggest that orbital subperiosteal abscess in rhinosinusitis patients is attributed to diVuse higher grades of ethmoidal sinus bony pyogenic osteitis. Staphylococcus aureus is the most commonly involved cultured bacteria. Bony osteitis in rhinosinusitis patients with SPOA is similar clinically and histopathologically in its character and behavior to osteomyelitis of bone all over the body with associated subperiosteal abscess.
To design and synthesize a novel class of protein tyrosine kinase inhibitors, featuring the N-(2-... more To design and synthesize a novel class of protein tyrosine kinase inhibitors, featuring the N-(2-oxo-1,2-dihydroquinolin-3-yl-methyl)-thiourea framework. Methods: First, compounds 1 and 2 were identified using the virtual screening approach in conjunction with binding assay based on surface plasmon resonance. Subsequently, 3 regions of compounds 1 and 2 were selected for chemical modification. All compounds were characterized potent inhibitory activities toward the human lung adenocarcinoma cell line SPAC1. Results: Forty new compounds (1-2, 3a-g, 4a-w, and 5a-l) were designed, synthesized and bioassayed. Six compounds (1, 3e, 4l, 4w, 5a, and 5b) were found to show promising inhibitory activity against the SPAC1 tumor cell line. The inhibitory activity of compound 5a increases approximately 10 times more than that of the original compound 1. Conclusion: This study provides a promising new template with potential antitumor activity. 1: R=6-Me, K D =1.46 µmol/L 2: R=7-Me, K D =80.7 µmol/L Figure 1. Structure of compounds 1-2, and 3 of their regions.
Aiad HAS, Kandil MAH, Samaka RM, Sultan MM, Badr MT, Nada GEM. The role of ck7, ki-67, cd34 and v... more Aiad HAS, Kandil MAH, Samaka RM, Sultan MM, Badr MT, Nada GEM. The role of ck7, ki-67, cd34 and vimentin in the differentiation between biliary atresia and idiopathic neonatal hepatitis in egyptian cholestatic neonates. APMIS 2012. The differentiation between biliary atresia (BA) and idiopathic neonatal hepatitis (INH) is challenging with many histological overlaps especially in the first weeks of life. This study aimed to investigate the role of immunohistochemical staining of CK7, Ki67, CD34, and vimentin in addition to other clinicopathological features in the differentiation between BA and INH. Cases included 30 infants with BA and 30 infants with INH. The diagnosis was based on clinical, laboratory, and liver biopsy examination. Female gender and elevated serum gamma glutamyle transferase were in favor of BA. Portal tract changes, such as bile ductular proliferation documented by CK7, Ki67 immunostaining and angiogenesis documented by CD34 immunostaining, favored the diagnosis of BA. Copper associated protein was positive in 70% of BA cases, but not detected in INH cases. Parenchymatous changes, such as giant cell transformation and positive iron deposition and Kupffer cell proliferation documented by vimentin immunostaining, favored the diagnosis of INH.CK7, Ki67, CD34, and vimentin are helpful adjuvant immunostaining in the differentiation between BA and INH.
Ephrin receptors and ephrin ligands constitute one of the largest groups of tyrosine kinases. The... more Ephrin receptors and ephrin ligands constitute one of the largest groups of tyrosine kinases. The division of ephrin receptors into type A or type B is determined by their ligand-binding specificities. Ephrin A4 as a ligand has a broad capacity to bind and stimulate different subtypes of ephrin A receptors. Little is known about the role of ephrins generally and ephrin A4 particularly in osteosarcoma. Ephrin A4 was immunohistochemically assessed on archival material from 46 primary osteosarcoma cases, 10 metastatic pulmonary lesions and 20 normal control bone specimens. Ephrin A4 was expressed in 100% of normal bone specimens, in 84.4% of primary osteosarcoma cases and in all metastatic pulmonary lesions. Cytoplasmic and nucleocytoplasmic patterns of ephrin A4 immunoreactivity were observed, with the predominance of the latter pattern in normal bone (100%), and in 43.5% of primary osteosarcoma cases, which showed a higher intensity of expression compared with normal bone (p&amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). The cytoplasmic pattern is the only staining pattern seen in metastatic cases, which may suggest its role in enhancement of invasion and metastasis. The differences in the distribution of the two patterns of ephrin A4 may indicate a different biological activity of this molecule depending on its localization. The nuclear localization of ephrin A4 requires further investigation to clarify the mechanism and the significance of the nuclear trafficking of ephrin A4.
To apply the immunohistochemical method using robust biomarkers; Gli1 & β catenin trying to i... more To apply the immunohistochemical method using robust biomarkers; Gli1 & β catenin trying to identify sonic hedgehog (SHH) & Wingless (WNT) active tumors. Also identification of the molecular subgroups of medulloblastoma has immediate clinical relevance guiding therapeutic stratification and the use of targeted therapies. This retrospective study was conducted on 49 tissue specimens of medulloblastoma cases for evaluation of immunohistochemical (IHC) expression of GLi1 and β-catenin. The studied cases showed absence of nuclear positivity of β catenin & 15/49 cases (30.6%) exhibited an activated sonic hedgehog signaling pathway (SHH) pronounced by nuclear positivity for Gli1. 34/49 cases (69.4%) cases that showed absence of nuclear reactivity for Gli1 and β catenin were considered as non SHH/WNT medulloblastoma group. There were no statistical significant differences between the 2 subgroups as regards to the clinical and histopathological features. Non SHH/WNT pathway identified via the absence of nuclear localization to either Gli1 & β catenin represents a major contributor to medulloblastoma in the studied Egyptian patients.
Skin tags (STs) are common benign dermal connective tissue neoplasms that are mainly composed of ... more Skin tags (STs) are common benign dermal connective tissue neoplasms that are mainly composed of loose fibrous tissue. However, their exact etiology is not fully understood. Leptin is a major player in the biology and pathology of the skin and its appendages. It is linked to cell differentiation, proliferation, migration, and survival with pronounced effects on angiogenesis, blood flow, and tissue perfusion. This study aimed at investigating the possible role of leptin in STs pathogenesis and correlating its expression with different clinical and histopathological parameters. Using immunohistochemical techniques, we examined 90 subjects. These included 60 non-obese cases with STs and 30 age-, gender- and Body Mass Index-matched normal subjects as a control group. Leptin was overexpressed in STs compared with normal skin (p < .001). Nuclear and nucleocytoplasmic patterns were significantly associated with cases both in epidermis (p < .04) and dermis (p < .001). Higher epider...
Carbonic anhydrase IX (CAIX) is an enzyme whose expression is very limited in normal tissues and ... more 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.
Analytical and quantitative cytopathology and histopathology, 2014
To elucidate the role of toll-like receptor 2 (TLR2) in the pathogenesis of acne vulgaris through... more To elucidate the role of toll-like receptor 2 (TLR2) in the pathogenesis of acne vulgaris through its immunohistochemical localization in inflammatory and noninflammatory lesions of this disease entity. Using standard immunohistochemical techniques, we examined 30 acne cases (involved and noninvolved skin) and the normal skin biopsies of 30 sex- and age-matched, healthy subjects representing the control group. All examined cases showed positive TLR2 expression in epidermis, pilosebaceous units and dermal inflammatory infiltrate. There were statistically significant differences between acne-involved skin and normal skin and between acne-involved and noninvolved skin regarding TLR2 expression intensity in pilosebaceous units (p < 0.001 for both) and dermal inflammatory infiltrate (p < 0.001 for both). Intense TLR2 expression was in favor of inflammatory acne lesions in pilosebaceous units (p = 0.03) and dermal inflammatory infiltrate (p < 0.05). Intense TLR2 expression was al...
Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of caveolae, sphing... more Caveolin-1 (CAV1) and caveolin 2 (CAV2) are the principal structural proteins of caveolae, sphingolipid and cholesterol-rich invaginations of the plasma membrane involved in vesicular trafficking and signal transduction. Over the recent years there has been controversy about their role in breast cancer and their suitability as markers of basal-like phenotype. Caveolin-1 and CAV2 protein expression was assessed on a tissue microarray containing 880 unselected invasive breast cancer cases, by means of immunohistochemistry. Caveolin-1 and CAV2 expression was observed in 13.4 and 5.9% of all breast cancer, respectively. Their expression was strongly associated with high histological grade, lack of steroid hormone receptor positivity (ER and PR), and expression of basal markers (basal cytokeratins, P63, P-cadherin). Furthermore, there was a significant association between CAV1 and CAV2 expression and basal-like phenotype. On univariate analysis only CAV2 had a prognostic impact on breast...
Journal of the Egyptian National Cancer Institute, 2006
Cyclooxygenase-2 (Cox-2) is the inducible form of cyclooxygenase enzyme. Cox-2 is induced in nume... more Cyclooxygenase-2 (Cox-2) is the inducible form of cyclooxygenase enzyme. Cox-2 is induced in numerous processes such as cellular growth, differentiation, inflammation and tumorogenesis. Assessment of Cox-2 expression in chronic gastritis and gastric carcinoma. Sixteen chronic gastritis (CG) and 43 gastric carcinoma cases were subjected to an immunohistochemical approach using anti Cox-2 antibody. All CG cases displayed positive epithelial Cox-2 expression with only 25% positivity for stromal expression. Eighty six percent of gastric carcinoma showed epithelial Cox-2 expression that was significantly correlated with lymph node involvement (p<0.01), advanced stage (p=0.01), high microvessel density (MVD) (p=0.0001), vascular invasion (p=0.002), perineural invasion (p=0.01) and low apoptotic count (p<0.0001). Stromal Cox-2 expression was seen in 79% of gastric carcinoma cases and was significantly associated with low apoptotic count (p=0.0007), vascular invasion (p=0.001) and hig...
Trichoepithelioma (TE) is a benign tumor of follicular origin that presents as small, skin-colore... more Trichoepithelioma (TE) is a benign tumor of follicular origin that presents as small, skin-colored papules predominantly on the face. When more than one family member is affected, the disease is known as multiple familial trichoepithelioma (MFT). It is a rare autosomal dominant (AD) skin disease. Malignant transformation is very rare. We present a case of MFT in a female patient and her father with malignant transformation to basal cell carcinoma (BCC) in the father. We summarized the main histological differential parameters between TE and BCC and applied immunophenotyping for both by administration of Bcl2, CD34, CD10 and androgen receptor (AR) antibodies.
Parachordoma is an extremely rare soft tissue tumor of unknown lineage. Parachordoma develops mos... more Parachordoma is an extremely rare soft tissue tumor of unknown lineage. Parachordoma develops most often on the extremities. Only 2 cases have been reported as pelvic parachordoma. A 46-year old Egyptian woman with a huge painful pelvic mass was found to have a parachordoma with ectopic pelvic right kidney. There is only one report in the literature of fine needle aspiration cytology in this setting. The microscopic picture of parachordoma is not new to pathologists but the gross picture of this rare tumor has not previously been published; not even in the World Health Organization classification of soft tissues tumors. Diagnosis was confirmed by immunohistochemistry. The patient is in good clinical condition without any evidence of recurrence or metastasis after 84 months of follow up.
The immunohistochemical (IHC) subtyping of breast cancer can be a useful substitute for gene expr... more The immunohistochemical (IHC) subtyping of breast cancer can be a useful substitute for gene expression analysis. The aim of this study was to investigate the relationship of CK8/18 to the biology of breast carcinoma (BC) represented by its IHC subtypes. The IHC expression of CK8/18 was correlated with IHC subtypes of BC using ER, PR, HER2/neu, and Ki67 LI (with cutoff 14%). All cases showed CK 8/18 expression in tumour cells with varying degree of intensities; 49/70 cases (70%) showed diffuse cytoplasmic expression (loss of membranous pattern), while 21/70 cases (30%) showed membrano-cytoplasmic pattern. Adjacent non-neoplastic breast lobules showed membrano-cytoplasmic pattern in 58% of cases, which was significantly different from the pattern in invasive cancer (P = 0.002). A loss of membranous pattern in malignant tumours was significantly associated with higher tumour grade (P = 0.02), higher mitotic count (P = 0.03), and negative HER2/neu status (P = 0.04). CK 8/18 H score ran...
Background: Lipoid proteinosis (Urbach-Wiethe disease) is a rare progressive autosomal recessive ... more Background: Lipoid proteinosis (Urbach-Wiethe disease) is a rare progressive autosomal recessive disorder, characterized histologically by deposition of periodic acid Schiff-positive, diastase resistant, hyaline-like material into the skin, upper aerodigestive tract, and internal organs.
Kaposi sarcoma (KS) is a neoplasm of the endothelial cells. It often manifests with multiple vasc... more Kaposi sarcoma (KS) is a neoplasm of the endothelial cells. It often manifests with multiple vascular nodules on the skin and other organs. It is a systemic, malignant and multifactorial disease and has a variable course. There are four types: classic, endemic, iatrogenic and HIV-associated. The primary presentation on the penis and face is uncommon and is mainly observed in HIV-positive patients. Multiple treatment modalities are used including surgery, cryotherapy, electrosurgery, laser and radiation therapy.
Wilms tumor is a mixed embroynal neoplasm of the kidney . HER2 is an onco-protein. Its over-expre... more Wilms tumor is a mixed embroynal neoplasm of the kidney . HER2 is an onco-protein. Its over-expression could be implicated in the development of many tumors. The clinico-demographic and pathological data of 28 Wilms tumor patients were , reviewed. The tissue samples were examined by light Microscopy then immunohistochemical staining for HER2/neu expression. Additional 28 normal surrounding renal tissue specimens were included. There was significant differences between HER2/neu positive and HER2/neu negative Wilms tumors in relation to stage, histological phase and epithelial differentiation (P>0.05 for all). The overall survival advantage was noticed if Wilms tumor was at early stages (I and II) (Log-rank=13.23 and P>0.001), homologous epithelial differentiation (Log-rank=6.01 and P=0.04), as well as HER2/neu positive tumors (Log-rank=6.14 and P=0.013). A statistical significant trend toward a longer recurrence free survival was, noticed if Wilms tumor was at early stages (Log-rank=21.22, P>0.0000) and if HER2/neu positive (Log-rank=8.53, P=0.004). HER2/neu expression in Wilms tumor could be a marker for epithelial and homologous differentiation and its expression could be a good predictor for overall survival and longer recurrence free survival.
Ephrin A4 is one of the ephrin ligand molecules belonging to the tyrosine kinases receptor family... more Ephrin A4 is one of the ephrin ligand molecules belonging to the tyrosine kinases receptor family. It was originally identified in a T-lymphoma cell line and seen to be expressed in human adult tissue as well as several tumor types. In our previous study, we showed the unique pattern of ephrin A4 immunohistochemical staining, which differed according to the type of examined bone specimens (normal bone, primary, and metastatic osteosarcoma lesions). The aim of the present study is to evaluate the prognostic impact of ephrin A4 expression in a group of primary osteosarcoma patients. Ephrin A4 immunohistochemical expression was carried out on 47 primary osteosarcoma cases. Ephrin A4 was expressed in 82.9% of osteosarcoma cases with cytoplasmic localization in 58.9% of positive cases. The cytoplasmic pattern was significantly associated with aggressive histopathological types of osteosarcoma (P = 0.02), advanced stage (P = 0.04), the presence of metastasis (P = 0.03), inferior response to neoadjuvent chemotherapy (P = 0.04), and tended to be associated with a shorter event-free survival (P = 0.09). The cytoplasmic pattern of ephrin A4 could identify a subgroup of primary osteosarcoma patients with a high liability for progression, poor prognosis, and inferior response to chemotherapy.
Multiple theories were described concerning the pathogenesis of orbital infection in rhinosinusit... more Multiple theories were described concerning the pathogenesis of orbital infection in rhinosinusitis, but no theory was proved. Understanding the cause of complication can allow its proper management. We speculate that subperiosteal orbital abscess (SPOA) secondary to rhinosinusitis is similar to subperiosteal abscess associated with osteomyelitis of bone all over the body. The objective was to evaluate bony changes of the ethmoidal sinuses in complicated rhinosinusitis patients with SPOA. This prospective controlled study was performed on eight patients undergoing endoscopic sinus surgery drainage for rhinosinusitis complicated with SPOA. Age, radiographic bony characteristics, and histopathological Wndings were all documented. Ethmoidal bone specimens were examined and assessed histopathologically. Purulence of SPOA was collected and sent for cultures. The authors evaluated normal ethmoidal bone specimens taken endoscopically from the medial wall of obstructing concha bullosa in ten control patients. The analysis revealed CT and histopathologic changes consistent with high grades of ethmoidal bone pyogenic osteitic changes. Coagulase-positive staphylococci were the predominant cultured bacteria (62.5%) in SPOA. These Wndings suggest that orbital subperiosteal abscess in rhinosinusitis patients is attributed to diVuse higher grades of ethmoidal sinus bony pyogenic osteitis. Staphylococcus aureus is the most commonly involved cultured bacteria. Bony osteitis in rhinosinusitis patients with SPOA is similar clinically and histopathologically in its character and behavior to osteomyelitis of bone all over the body with associated subperiosteal abscess.
To design and synthesize a novel class of protein tyrosine kinase inhibitors, featuring the N-(2-... more To design and synthesize a novel class of protein tyrosine kinase inhibitors, featuring the N-(2-oxo-1,2-dihydroquinolin-3-yl-methyl)-thiourea framework. Methods: First, compounds 1 and 2 were identified using the virtual screening approach in conjunction with binding assay based on surface plasmon resonance. Subsequently, 3 regions of compounds 1 and 2 were selected for chemical modification. All compounds were characterized potent inhibitory activities toward the human lung adenocarcinoma cell line SPAC1. Results: Forty new compounds (1-2, 3a-g, 4a-w, and 5a-l) were designed, synthesized and bioassayed. Six compounds (1, 3e, 4l, 4w, 5a, and 5b) were found to show promising inhibitory activity against the SPAC1 tumor cell line. The inhibitory activity of compound 5a increases approximately 10 times more than that of the original compound 1. Conclusion: This study provides a promising new template with potential antitumor activity. 1: R=6-Me, K D =1.46 µmol/L 2: R=7-Me, K D =80.7 µmol/L Figure 1. Structure of compounds 1-2, and 3 of their regions.
Aiad HAS, Kandil MAH, Samaka RM, Sultan MM, Badr MT, Nada GEM. The role of ck7, ki-67, cd34 and v... more Aiad HAS, Kandil MAH, Samaka RM, Sultan MM, Badr MT, Nada GEM. The role of ck7, ki-67, cd34 and vimentin in the differentiation between biliary atresia and idiopathic neonatal hepatitis in egyptian cholestatic neonates. APMIS 2012. The differentiation between biliary atresia (BA) and idiopathic neonatal hepatitis (INH) is challenging with many histological overlaps especially in the first weeks of life. This study aimed to investigate the role of immunohistochemical staining of CK7, Ki67, CD34, and vimentin in addition to other clinicopathological features in the differentiation between BA and INH. Cases included 30 infants with BA and 30 infants with INH. The diagnosis was based on clinical, laboratory, and liver biopsy examination. Female gender and elevated serum gamma glutamyle transferase were in favor of BA. Portal tract changes, such as bile ductular proliferation documented by CK7, Ki67 immunostaining and angiogenesis documented by CD34 immunostaining, favored the diagnosis of BA. Copper associated protein was positive in 70% of BA cases, but not detected in INH cases. Parenchymatous changes, such as giant cell transformation and positive iron deposition and Kupffer cell proliferation documented by vimentin immunostaining, favored the diagnosis of INH.CK7, Ki67, CD34, and vimentin are helpful adjuvant immunostaining in the differentiation between BA and INH.
Ephrin receptors and ephrin ligands constitute one of the largest groups of tyrosine kinases. The... more Ephrin receptors and ephrin ligands constitute one of the largest groups of tyrosine kinases. The division of ephrin receptors into type A or type B is determined by their ligand-binding specificities. Ephrin A4 as a ligand has a broad capacity to bind and stimulate different subtypes of ephrin A receptors. Little is known about the role of ephrins generally and ephrin A4 particularly in osteosarcoma. Ephrin A4 was immunohistochemically assessed on archival material from 46 primary osteosarcoma cases, 10 metastatic pulmonary lesions and 20 normal control bone specimens. Ephrin A4 was expressed in 100% of normal bone specimens, in 84.4% of primary osteosarcoma cases and in all metastatic pulmonary lesions. Cytoplasmic and nucleocytoplasmic patterns of ephrin A4 immunoreactivity were observed, with the predominance of the latter pattern in normal bone (100%), and in 43.5% of primary osteosarcoma cases, which showed a higher intensity of expression compared with normal bone (p&amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). The cytoplasmic pattern is the only staining pattern seen in metastatic cases, which may suggest its role in enhancement of invasion and metastasis. The differences in the distribution of the two patterns of ephrin A4 may indicate a different biological activity of this molecule depending on its localization. The nuclear localization of ephrin A4 requires further investigation to clarify the mechanism and the significance of the nuclear trafficking of ephrin A4.
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