Biomedical subjects

Muna Sabah

Publications and source records attributed to Muna Sabah.

12 recordsLinked to original sources

PubMed2006

Para-testicular cellular angiofibroma: a rare tumour in a male renal transplant patient.

Cellular angiofibroma is a rare, benign, mesenchymal neoplasm that should be distinguished from other more aggressive mesenchymal lesions. A 32-year-old male presented with a painless para-testicular mass. Pathological examination showed features characteristic of cellular angiofibroma. He had a history of renal transplantation and was on immunosuppressive drugs. The pathogenesis of cellular angiofibroma is largely undetermined. The role of immunosuppressive therapy in the genesis of this tumour awaits further analysis.

Adult↗

PubMed2006

Altered expression of cell cycle regulatory proteins in gastrointestinal stromal tumors: markers with potential prognostic implications.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract. The prediction of the malignant potential of GISTs is still difficult. Altered cell cycle regulation may underlie the tumorigenesis and/or the progression of human malignancies. Although p53 and Bcl-2 have been extensively investigated in GISTs, little is known about the frequency of expression and possible clinical implications of alterations of other cell cycle regulatory proteins in these neoplasms. We have previously investigated the role of loss of p16(INK4A) by loss of heterozygosity and immunohistochemistry in the progression of GISTs and found that loss of heterozygosity of 9p and loss of p16 expression are confined to malignant GISTs. This has led us to investigate the role of other cell cycle regulatory proteins in these tumors. Twenty-three cases of GIST (9 low malignant potential [LMP], 10 primary malignant, and 4 intra-abdominal recurrences) were examined. All cases were strongly positive for KIT (CD117). Immunohistochemical stains were carried out on tissue microarrays to evaluate the expression of proteins involved in the G(1)-S transition and proteins that regulate apoptosis including Rb, E2F1, cyclin D1, CDK4, CDK6, p27(KIP1), p21(WAF1/CIP1), p53, Mdm2, Bcl-2, and Bax. The positive phenotypes identified were as follows: Rb, 39.1%; E2F1, 69.6%; cyclin D1, 30.4%; CDK4, 100%; CDK6, 30.4%; 39.1%; p27(KIP1), 47.8%; p21(WAF1/CIP1), 39.1%; p53, 43.5%; Mdm2, 17.4%; Bcl-2, 91.3%; and Bax, 100%. Malignant GISTs are more likely to be associated with a positive E2F1 and p53 phenotype and a negative p16 and p27(KIP1) phenotype. It was concluded that aberration of the cell cycle regulators is a frequent finding and may be a contributing factor to the pathogenesis of GISTs. While some alterations are seen in LMP and malignant GISTs and therefore may represent an early event in molecular tumorigenesis of GISTs, other alterations are more common in malignant GISTs than LMP and therefore have potential utility as complementary tools for the prognostication of GISTs.

Adult↗

PubMed2006

Loss of p16 (INK4A) expression is associated with allelic imbalance/loss of heterozygosity of chromosome 9p21 in microdissected malignant peripheral nerve sheath tumors.

The p16 is a tumor suppressor gene on the short arm of chromosome 9p21. The product of the p16 acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein. This study was designed to assess the frequency of genetic loss of 9p21 and to determine the role of p16 the pathogenesis of sporadic and neurofibromatosis 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNSTs). The authors examined 15 cases for p16 protein expression and 10 cases for allelic imbalance (AI)/loss of heterozygosity (LOH) of chromosome 9p. DNA was microdissected from normal and neoplastic tissues. AI/LOH analysis was performed using six microsatellite markers on the 9p region. On immunohistochemical analysis 80% of cases showed abnormal expression of p16. Similarly, 8 of 10 cases revealed genetic loss with at least one microsatellite marker. The most frequent deletion was that within the coding sequence. Of p16 at me D9S974 locus. These findings emphasize the role of loss of p16 in the development of both sporadic and NF1-associated MPNSTs.

Adolescent↗

PubMed2006

Immunohistochemical detection of hTERT protein in soft tissue sarcomas: correlation with tumor grade.

Human telomerase reverse transcriptase (hTERT) is a telomerase catalytic subunit that regulates telomerase activity. Telomerase is expressed in many human cancers and cell lines and is thought to contribute to their immortality. Little is known about the expression of telomerase in non-epithelial tumors. The objective of this study was to evaluate hTERT expression in a wide range of soft tissue sarcomas. A total of 154 cases of different types of soft tissue sarcoma (54 low-grade, 40 intermediate-grade, and 60 high-grade cases) were evaluated for hTERT expression using immunohistochemistry on tissue microarrays. hTERT immunoexpression was detected in 59% of cases; it was observed in 46%, 58%, and 72% of low-grade, intermediate-grade, and high-grade sarcoma cases, respectively. The intensity of staining positively correlated with the grade of the sarcomas: diffuse strong positive nuclear staining was identified in 6, 8, and 30 cases of low-grade, intermediate-grade, and high-grade sarcomas, respectively. These results suggest that telomerase expression is more often detected in highly malignant tumors than in low-grade sarcomas and thus may be a critical mechanism in tumor progression.

Humans↗

PubMed2006

Aberrant expression of the Rb pathway proteins in soft tissue sarcomas.

Cell cycle regulation depends on a fine balance between cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CKIs) that block the cycle progression. Alterations of the cell cycle regulators are a common feature of many malignant tumors, and some have been shown to have prognostic significance. In this study, 152 cases of different types of soft tissue sarcomas were evaluated for alterations of cell cycle regulator proteins that control the cell cycle progression from G1 to S phase and govern the Rb pathway. Immunohistochemical stains for proteins Rb, E2F1, cyclin D1, CDK4, CDK6, p16, and p27 were carried out on tissue microarrays. The relationship between the expression of these proteins and the histologic grade of the sarcomas was assessed. Altered expression for Rb and p16 proteins was identified in 67.8% and 65.1% of the cases, respectively. Overexpression of E2F1, cyclin D1, CDK4, and CDK6 was detected in 50.7%, 24.3%, 92.1%, and 10.5%, respectively. Overexpression of E2F1 was associated with altered expression of Rb protein. Overexpression of cyclin D1, CDK4, and CDK6 showed an association with normal Rb expression. CDK6 expression revealed a positive correlation with the histologic grade of the sarcoma, and p27 expression was inversely correlated with sarcoma grade. These results suggest that alterations of the Rb pathway proteins are common in soft tissue sarcomas and may participate in their tumorigenesis. CDK6 and p27 showed correlation with the histologic grade of the sarcomas, suggesting that these proteins could be used as prognostic markers.

Biomarkers, Tumor↗

PubMed2005

Loss of p16INK4A expression is associated with allelic imbalance/loss of heterozygosity of chromosome 9p21 in microdissected synovial sarcomas.

Deletions of the short arm of chromosome 9 have been observed in many tumours and cell lines. This chromosomal region is frequently targeted during malignant transformation because it contains at least two known tumour suppressor genes: p16(INK4) and p15(INK4B). p16(INK4A) acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein and therefore block the progression of the cell cycle from G1 to S phase. The role of p16(INK4A) in the development of synovial sarcoma has not been comprehensively investigated. Ten samples of synovial sarcomas were examined for allelic imbalance/loss of heterozygosity (AI/LOH) of the 9p region and p16 protein expression. DNA was isolated from microdissected sections of normal and tumour cells, amplified by polymerase chain reaction and analysed for AI/LOH by using six microsatellite markers that map to the 9p region. Immunohistochemistry for p16 expression was done. AI/LOH with at least one microsatellite marker on 9p21 was detected in six of ten samples. The most frequent allelic deletions were observed within the coding sequence of p16(INK4A). Loss of p16 immunoreactivity was detected in eight samples, six of which showed evidence of alterations at 9p21 region. These findings suggest a possible role of loss of p16(INK4A) in the development of synovial sarcoma.

Chromosomes, Human, Pair 9↗

PubMed2005

Leiomyosarcoma and malignant fibrous histiocytoma share similar allelic imbalance pattern at 9p.

Formalin-fixed, paraffin-embedded tissue from 45 soft tissue sarcomas was analysed for allelic imbalance/loss of heterozygosity (AI/LOH) of chromosome 9. The specimens consisted of 17 cases of soft tissue leiomyosarcoma (LMS), 4 cases of cutaneous LMS, 22 cases of conventional malignant fibrous histiocytoma (MFH) and 2 cases of angiomatoid fibrous histiocytoma. All cases were categorised morphologically and immunohistochemically. DNA was microdissected from normal and neoplastic tissues. AI/LOH was performed using six microsatellite markers on the 9p region. The frequency of allelic imbalance at different loci on chromosome 9p was analysed in LMS and MFH and then compared with values previously examined in synovial sarcoma and malignant peripheral nerve sheath tumour. Although AI/LOH and microsatellite instability (MSI) were more frequent in MFH, LMS and MFH groups showed similar patterns of allelic imbalance at the 9p region. Alterations of chromosome 9p have been reported in many cell lines and tumours including LMS and MFH. 9p21 region encodes p16(INK4A) and p15(INK4B). Allelic imbalance observed at 9p 21 in this study suggests that alterations of the negative cell cycle regulators may be an important step in the pathogenesis of MFH and LMS. However, the most frequent allelic imbalance was observed at 9p24 at D9S230. Alterations of this locus were very rare in synovial sarcoma and malignant peripheral nerve sheath tumours and were absent in cutaneous LMS and angiomatoid fibrous histiocytoma. This locus may point to the existence of a genetically altered tumour suppressor gene involved in the pathogenesis of LMS and MFH. Our results support the hypothesis that MFHs may represent a morphological pathway in tumour progression of LMSs.

Allelic Imbalance↗

PubMed2005

Toxic epidermal necrolysis secondary to angioimmunoblastic T-cell lymphoma.

A 67-year-old man presented with a history of lymphadenopathy, fevers and separate skin eruptions of erythrodermic spongiotic dermatitis initially and subsequent toxic epidermal necrolysis. Initial lymph node biopsies showed non-specific granulomatous changes, and skin biopsies and bone marrow aspirate were not diagnostic. His toxic epidermal necrolysis responded well to 3 days of intravenous immunoglobulin. The patient was discharged from hospital and reviewed regularly as an outpatient. Due to persisting lymphadenopathy, further lymph node biopsy led to the diagnosis of angioimmunoblastic T-cell lymphoma, a rare form of peripheral T-cell lymphoma with a poor prognosis. At the time of diagnosis his condition deteriorated rapidly and he died soon after.

Aged↗

PubMed2004

Expression of human telomerase reverse transcriptase in gastrointestinal stromal tumors occurs preferentially in malignant neoplasms.

Telomerase is expressed in many human cancers and cell lines and is thought to contribute to their immortality. To date, little is known about the expression of telomerase in nonepithelial tumors. The objective of this study was to evaluate the expression of human telomerase reverse transcriptase (hTERT) in gastrointestinal stromal tumors (GISTs). Twenty-three GISTs (9 low malignant potential, 10 primary malignant, and 4 intra-abdominal recurrences) were evaluated for hTERT expression by using immunohistochemistry on tissue microarray. Tissue blocks were retrieved, and hematoxylin and eosin stains were performed to evaluate the histological tumor type. All cases were strongly positive for KIT (CD117). Immunohistochemistry for hTERT was performed. Eight of 9 cases of the low malignant potential group were negative for hTERT immunoexpression, whereas all malignant GISTs showed positive staining that varied from weak to strong immunoreactivity. Six of 10 cases of the primary malignant GISTs were strongly positive for hTERT. The remaining cases (4/10) showed weak staining. All recurrent GISTs (4/4) showed strong positive immunostaining for hTERT. One malignant case was weakly positive for hTERT, but its recurrence was strongly positive. These results suggest that hTERT expression occurs preferentially in malignant tumors and that telomerase activity may occur during the progression of GISTs. Immunohistochemical staining for hTERT may be a useful marker for the prognostication of GISTs.

Adult↗

PubMed2004

Loss of heterozygosity of chromosome 9p and loss of p16INK4A expression are associated with malignant gastrointestinal stromal tumors.

Gastrointestinal stromal tumors GISTs are distinctive KIT-positive mesenchymal neoplasms. The genetic alterations leading to the malignant behavior of these tumors are not well characterized. In this study, 21 cases of GISTs (eight low malignant potential, nine primary malignant and four intra-abdominal recurrences) were characterized by immunohistochemistry and evaluated for loss of heterozygosity of the short arm of chromosome 9, using six microsatellite markers. Loss of heterozygosity with at least one microsatellite marker at 9p region was a common finding in high-risk GISTs (malignant and recurrent group) but was absent in the low malignant potential group. Recurrent GISTs showed more frequent deletions than their primary tumors. All cases with loss of heterozygosity showed deletions at 9p21. Similarly, all low malignant potential GISTs were immunoreactive for p16, whereas malignant tumors were negative for p16. These results suggest that loss of p16(INK4A) gene on 9p may contribute to the progression and/or malignant transformation of GISTs.

Adult↗

PubMed2003

Cyclooxygenase-2 expression in stromal tumors of the gastrointestinal tract.

Cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid to prostaglandins, prostacyclin, and thromboxane. COX-2 is expressed in many epithelial malignancies, particularly those of the gastrointestinal (GI) tract. COX-2 has been implicated in the pathogenesis of cancers and has a significant negative effect on survival. To date, little is known about the expression of COX-2 in nonepithelial tumors. The objective of this study was to evaluate the expression of COX-2 in GI stromal tumors (GISTs). We evaluated 15 GISTs using tissue microarray. Tissue blocks were retrieved and stained with hematoxylin and eosin to evaluate the histological tumor type. In addition, immunohistochemistry was performed for COX-2, the macrophage marker, CD68 (KP-1), and KIT (CD117). Two pathologists then evaluated the tissues to determine the extent and intensity of COX-2 expression. The location of CD68-positive cells, and whether these cells were COX-2 positive, was also evaluated. The results showed that 80% (12 of 15) of the tumors expressed COX-2. Expression was noted in the cytoplasm of the tumor cells, with variable intensity of staining among the tumors. COX-2 was expressed in both epithelial cell and spindle cell tumors, but appeared stronger in epithelial lesions. In mixed lesions, COX-2 was expressed to a greater extent in epithelial areas. There was a greater extent of COX-2 expression in malignant tumors and tumors located within the stomach. Tumor-infiltrating macrophages (CD68-positive cells) were identified in all of the lesions; in 80% of cases, those macrophages also expressed COX-2. This study is the first to demonstrate COX-2 expression in stromal lesions of the GI tract. The enzyme may play a role in the proliferation of these lesions, suggesting the potential use of nonsteroidal anti-inflammatory drugs in treatment.

Antigens, CD↗

PubMed2003

The problem with KIT: clinical implications and practical difficulties with CD117 immunostaining.

Immunohistochemical staining for KIT (CD117) was performed on 144 cases of soft tissue sarcoma and 11 cases of gastrointestinal stromal tumor (GIST). Diffuse global staining in almost all neoplastic cells was a consistent feature of GIST but was also seen in some types of soft tissue sarcoma that resemble GISTs morphologically, such as synovial sarcoma and leiomyosarcoma. This finding is of diagnostic importance because some of these sarcoma types may involve the intestinal wall and simulate primary GIST. Most other positive cases showed focal staining. Although focal positivity may not be a problem in resected specimens, it has the potential to be misleading in biopsy material. Our results are concordant with some reports of CD117 expression in soft tissue tumors, but they differ from those reported by other laboratories. This discrepancy in the literature may be the result of variation in antibodies used or variation in immunohistochemical staining protocol. Regardless of the technical or scientific explanation, an understanding of the difficulties with KIT immunostaining is critical. Not only is KIT positivity used as a prerequisite for the diagnosis of GISTs, but treatment eligibility for STI571 in patients with GIST, and increasingly with other tumors, relies on positive KIT immunostaining.

Gastrointestinal Neoplasms↗