Aydanur Kargi

The diagnostic value of TTF-1, CK 5/6, and p63 immunostaining in classification of lung carcinomas.

This study was aimed to evaluate the utility of a panel of antibodies, consisting of thyroid transcription factor-1 (TTF-1), p63, and cytokeratins (CK) 5/6 for distinguishing between small cell lung carcinoma (SCLC) and nonsmall cell lung carcinoma, as well as for identifying glandular or squamous differentiation in small tissues obtained by bronchoscopy. Bronchoscopic biopsies of 77 lung carcinoma cases with easily recognizable morphologic features were included in this study. All the cases were immunohistochemically stained for p63, CK5/6 [indicators of squamous cell carcinoma (SCC)] and TTF-1 [indicator of SCLC and adenocarcinoma (AC)]. Although, 28 SCLC displayed TTF-1 positive, p63 negative immunoprofile, most of the SCC (32/39) had the opposite immunoprofile. All of the 10 ACs were negative for p63 and most of them (8/10) were negative for CK5/6. p63 and CK 5/6 seem to be useful for differentiating AC and SCLC from SCC with 100% specificity and 82% sensitivity, 89% specificity and 79% sensitivity, respectively. It seems that to achieve histologic typing of lung cancer as accurate as possible, TTF-1 in combination with p63 and CK 5/6 might be useful components of immunohistochemical analysis of poorly differentiated lung carcinomas in biopsy tissues.

HGF/c-Met Overexpressions, but not Met Mutation, Correlates with Progression of Non-small Cell Lung Cancer

Hepatocyte Growth Factor (HGF) and its receptor c-Met are suggested to play an important role in progression of solid organ tumors by mediating cell motility, invasion and metastasis. Overexpression of HGF and c-Met have been shown in non-small-cell lung cancer (NSCLC). However, their role in tumor progression is not clearly defined. The aim of this study is to determine the role of HGF/c-Met pathway and its association with invasion related markers and clinicopathologic parameters in NSCLC. Immunohistochemical analysis was performed on 63 paraffin-embedded NSCLC tumor sections. The expressions of invasion related markers such as Matrix Metalloproteinases (MMPs) 2 and 9, Tissue Inhibitor Metalloproteinase (TIMP) 1 and 3 and RhoA were also examined. Co-expression of HGF/c-Met was significantly associated with lymph node invasion and TIMP-3 and RhoA overexpressions. There were positive correlation between TIMP-3 overexpression and advanced stage and negative correlation between RhoA overexpression and survival. DNA sequencing for Met mutations in both nonkinase and tyrosine kinase (TK) domain was established. A single nucleotide polymorphism (SNP) in sema domain and two SNPs in TK domain of c-Met were found. There was no statistically significant correlation between the presence of c-Met alterations and clinicopathologic parameters except shorter survival time in cases with two SNPs in TK domain. These results suggest that HGF/c-Met might exert their effects in tumor progression in association with RhoA and probably with TIMP-3. The blockade of the HGF/c-Met pathway with RhoA and/or TIMP-3 inhibitors may be an effective therapeutic target for NSCLC treatment.

Bax, bcl-2 and c-kit expression in non-small-cell lung cancer and their effects on prognosis

In non‐small‐cell lung cancer (NSCLC), stage of the disease is still the most important prognostic factor. Other than stage, many biological markers and many other prognostic factors are studied to define their effects on prognosis of lung cancer. In this study, we aimed to evaluate the expressions of Bax and bcl‐2 genes which are important in apoptosis and c‐kit, which is a tyrosine kinase transmembrane receptor, as well as searched their response to treatment modalities and effects on survival.

The development of pulmonary adenocarcinoma in a patient with Job's syndrome, a rare immunodeficiency condition.

The hyperimmunoglobulin E (HIE) (Jobs) syndrome often has it onset in childhood and is characterized by markedly elevated serum IgE levels, chronic dermatitis and recurrent pyogenic infections. Lymphoid malignancies have most commonly been associated with this syndrome while the first case in the literature of carcinoma associated with HIE syndrome was a squamous cell carcinoma of the vulva, described by Clark et al. in 1998. We observed a male patient with Jobs syndrome diagnosed at age three who presented with bone pain and a metastatic epithelial tumor of the bone revealed by biopsy. Diagnostic procedures aimed at detecting the primary site showed multiple mediastinal lymph nodes with lung and liver metastases on computed tomography scans and an extradural spinal metastasis at the upper thoracic level on magnetic resonance imaging. Although the patient refused a bronchoscopic procedure, a diagnosis of pulmonary adenocarcinoma was established on the basis of sputum cytology and the clinical aspects of tumor extent. Intravenous corticosteroids and palliative radiotherapy were given for the spinal metastasis. Palliative chemotherapy could not be started because of the patients poor performance status as well as nosocomial fungal pneumonia and pseudomonal urogenital infection with bacteremia. Despite the antifungal and broad-spectrum antimicrobial treatments, the patient died of pseudomonal sepsis.

Acute trichinellosis in children compared with adults.

Objectives: Trichinellosis is a cosmopolitan parasite infection caused by Trichinella nematodes that is acquired from consumption of raw meat from several animal species. Knowledge of the clinical pattern and laboratory features of the disease in childhood is limited. The purpose is to study the clinical pattern of trichinellosis caused by Trichinella britovi in children and to compare it in household adults. Methods: We evaluated all children up to 17 years of age and their adult householders exposed to the consumption of infected meat during an outbreak of trichinellosis. A questionnaire was developed to record clinical data. The blood sample was collected for blood count, muscle enzymes, serum electrolytes, albumin and serology. All exposed children were treated with mebendazole, and severe symptomatic patients received prednisolone. Clinical and laboratory presentations and outcome were recorded. To evaluate the clinical picture of trichinellosis in childhood, clinical and laboratory findings were compared between children and household adults with a confirmed diagnosis who consumed the same amount of infected meat. Results: In 47 (62%) of 76 children with suspected trichinellosis, the diagnosis was serologically confirmed. The main clinical and laboratory findings in children were fever, abdominal pain, myalgia, facial and/or eyelid edema, rash, eosinophilia and increased muscular enzymes. The incubation period was similar in children and adults, but myalgia (66% versus 96%, P < 0.01), facial and/or eyelid edema (57% versus 86%, P < 0.05), eosinophilia (52% versus 96%, P < 0.01) and increased serum creatine kinase (38% versus 79%, P < 0.01) were less common in children than in adults. Seroconversion occurred in fewer children than adults, but the difference was not statistically significant. Conclusions: T. britovi infection shows a benign course and a milder clinical picture in children than in adults who consumed the same amount of infected meat.

Investigation of p53, c-erbB-2, PCNA immunoreactivity, DNA content, AgNOR and apoptosis in bladder carcinoma as prognostic parameters

The association between known prognostic variables such as TNM stage, histological grade and mutant p53 tumor suppressor gene product, c-erbB-2 oncoprotein, DNA ploidy and cell kinetic data, including mitoses, PCNA expression, AgNOR scores and apoptosis, was investigated in 29 transitional cell carcinoma (TCC) cases. A positive correlation between the histologic grade and all the studied parameters, except for c-erbB-2 expression, and a positive correlation between the stage and histological grade, DNA ploidy, mitoses, apoptosis and p53 expression were found. The results of this study are in accordance with some of the previous studies, except for apoptosis which had been studied for the first time in TCCs. Although we found a statistically significant correlation between the apoptosis and both tumor stage and histological grade, the predictive value of apoptosis as an independent prognostic factor remains to be established in a larger series.

Prognostic significance of immunohistochemical classification of diffuse large B-cell lymphoma

Abstract Aim: To evaluate the clinical significance of immunoperoxidase staining for CD10, bcl-6, mum-1 and bcl-2 to subdivide DLBCL into prognostic subgroups, we analysed 50 DLBCL cases using immunohistochemical methods. Methods and results: Fifty DLBCL patients were evaluated retrospectively. The expression of CD10 was associated with better OS (p=0·04) whereas expression of mum-1 was associated with worse OS (p=0·009). There were no significance of OS in case of expression of bcl-6 (p=0·05) and bcl-2 (p=0·3). They were subclassified using CD10, mum-1, bcl-6 as germinal center B-cell like (GCB) lymphoma (30%) and non-GCB lymphoma (70%). The OS and EFS (event free survival) were longer in GCB group (p=0·002) and 5-year OS for GCB group was 92% compared with only 44% for the non-GCB group (p=0·02). The OS of the GCB group also was longer compared to that of the non-GCB group in low IPI subgroup (p=0·01). Conclusion: The existance of survival differences between GCB a non-GCB group also in the patients with low IPI score, showed the importance of prognostic classification in the risk-adaptive treatment approaches. The classification as GCB and non-GCB based immunostains may enable to define more accurate prognostic groups in DLBCL.

Focal adhesion kinase (FAK) expression in normal and neoplastic lymphoid tissues.

Focal adhesion kinase (FAK) is a protein tyrosine kinase essential for intracellular regulatory events, such as cell growth, differentiation, migration and tumor metastasis. The aim of this study was to analyze the expression of FAK protein in a series of normal and neoplastic lymphoid tissues. An anti-FAK antibody was used to study the protein expression in paraffin-embedded samples of normal and neoplastic, hematolymphoid and non-hematolymphoid tissues by immunohistochemistry. In normal hematolymphoid tissue, the strongest expression of FAK was detected in germinal center and marginal-zone B cells; positive staining was also found in mantle zone B cells. In human lymphomas, FAK was expressed mostly in B-cell lymphomas and was predominantly negative in T-cell lymphoma. In Hodgkin lymphomas, FAK was found only in the neoplastic cells of lymphocyte predominant type, whereas the tumor cells of the classical form were FAK-negative. We demonstrate for the first time the expression of FAK in paraffin-embedded hematolymphoid tissue samples. Its differential expression in lymphomas may be of relevance for some B-cell neoplasms by using it as an additional marker to distinguish B- from T-lymphoblastic leukemia/lymphoma to further differentiate lymphocyte predominant from classical Hodgkin lymphoma.

Atypical infectious mononucleosis in a patient receiving tumor necrosis factor alpha inhibitory treatment

The objective is to report a case of atypical acute infectious mononucleosis in a juvenile ankylosing spondylitis patient who was treated with infliximab. A 20-year-old man was hospitalized for the evaluation of lymphadenopathy and systemic symptoms. His symptoms developed at the eighth week of the infliximab treatment and he required hospitalization. Lymph node biopsy was performed and he was diagnosed as atypical infectious mononucleosis (absence of fever, pharyngitis, lymphocytosis and negative atypical lymphocytosis on blood smear). Infections have become major concerns in patients treated with TNF-blocking agents. In theoretical base, it is not surprising as TNF-α has a crucial role in the body’s defense against both bacterial and viral invasion. Blocking the action of TNF may also change the course of the disease and could lead to a delay in the diagnosis. TNF-α-blocking treatment may mask the typical symptoms of infectious mononucleosis and atypical cases should be included in the differential diagnosis of lymphadenopathy in patients receiving anti-TNF-α agents.

Diabetes insipidus caused by pituitary gland metastasis accompanied by iris metastasis of small cell lung cancer: case presentation and review of the literature

Metastasis to the pituitary gland and iris is rarely seen in cancer patients. Breast cancer and lung cancer are the most common tumors that metastasize to these sites. Most lung cancer patients have non-small cell lung cancer and metastasis of small cell lung cancer to the pituitary gland and iris have been very rarely reported in the literature. Here we present a case of iris metastasis and pituitary gland metastasis which caused diabetes insipidus in a patient with small cell lung cancer.