IRS-2 G1057D polymorphism in Turkish patients with colorectal cancer.

INTRODUCTION: Gene polymorphisms have a broad range of analysis, but are of particular use in molecular medicine due to their potential in revealing the genetic tendency in diseases such as cancer, heart attack etc. These studies basically depend on mutations that can be detected by proper techniques. The genes coding the insulin receptor substrate (IRS) proteins are among the most widely analysed polymorphisms in various cancer types, in which a G1057D mutation is seen. AIM: To determine the risk of colon cancer by analysing the IRS-2 gene polymorphism in Turkish patients. MATERIAL AND METHODS: A total of 161 newly diagnosed colorectal cancer patients were analysed and compared to 197 unrelated healthy controls. A polymerase chain reaction-based restriction fragment length polymorphism method was carried out. RESULTS: No differences were observed between the patient and control groups for both allele and genotype frequencies of the IRS-2 G1057D gene. CONCLUSIONS: Our results demonstrated that IRS-2 G1057D polymorphism is not associated with colorectal cancer in the Turkish population. This research is a preliminary and original study in Turkish patients with colorectal cancer. It also provides population-level genetic data on IRS-2 in the Turkish population. Further studies should be performed on larger number of patients and controls for more reliable results about the genetic tendency in colorectal cancer in Turkey. The study is a collaborative work of different universities and scientists.

Taurine suppresses oxidative stress-potentiated expression of lectin-like oxidized low-density lipoprotein receptor and restenosis in balloon-injured rabbit iliac artery.

1. In endothelial cells, the major receptor for the binding and internalization of oxidized low-density lipoprotein (LDL) is the lectin-like oxidized LDL receptor (LOX-1). The aim of the present study was to investigate the effects of taurine on intimal thickening and LOX-1 expression under normal and oxidative conditions. 2. The iliac artery of rabbits were subjected to balloon injury and oxidative stress was induced by 14 days treatment of rabbits with 75 mg/kg, s.c., buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis. Taurine was administered in drinking water (1%, w/v) for 14 days in the presence (BSO + Taurine group) and in the absence of BSO treatment (Taurine group). In taurine and placebo groups, rabbits were injected with 4 mL, s.c., 0.9% NaCl (vehicle for BSO) for 14 days. 3. Taurine (1% in drinking water, w/v) preserved plasma levels of anti-oxidants and lowered the increased blood pressure induced by BSO. The stenosis rate of 29.92% in the placebo group increased to 72.20% in the BSO group, which was significantly reduced to 42.21% by taurine (P < 0.001; n = 5). Localization of LOX-1 to the intima and media of the iliac artery was demonstrated in the present study. Taurine treatment reduced the BSO-induced increase in LOX-1 expression at both the protein and mRNA levels (P < 0.05 and P < 0.01, respectively). 4. The results demonstrate that the stenosis rate and LOX-1 expression correlate well with oxidative status. Manipulation of LOX-1 expression by taurine may have therapeutic benefits in preventing restenosis.

Tumor grade-related thallium-201 uptake in chondrosarcomas.

OBJECTIVES: Diagnosis of low-grade chondrosarcoma, especially discrimination between enchondroma and low-grade chondrosarcoma, may be difficult pathologically. The aim of this study was to evaluate the value of thallium-201 (Tl-201) scintigraphy in the diagnosis of chondrosarcoma and to investigate whether there was a correlation between Tl-201 uptake and tumor grade. METHODS: We retrospectively evaluated 121 patients with pathologically proven bone and soft tissue tumors diagnosed between the years 1999 and 2007. All patients were followed by the Bone and Soft Tissue Tumor Working Group in our hospital. Twenty-three patients, mean age 44 +/- 15 (range 17-72) years, with a diagnosis of cartilaginous tumors were included. Increased Tl-201 uptake at the lesion sites greater than background was evaluated as malignant tumor. For the pathologic classification, a grading system (grade 1-3) based on the histopathologic findings was used. Pearson correlation coefficient was used to determine whether there was any correlation between Tl-201 uptake and tumor grade in chondrosarcoma. RESULTS: There were 7 enchondromas and 16 chondrosarcomas. Four of 16 patients with chondrosarcoma had lesions pathologically classified as grade 3, 5 as grade 2, and 7 had grade 1 chondrosarcoma. Increased Tl-201 uptake was observed in all patients with grade 3 chondrosarcoma and 2 patients with grade 2 chondrosarcoma. Of 10 patients with chondrosarcoma, 3 grade 2 chondrosarcomas and 7 grade 1 chondrosarcomas, there was no Tl-201 uptake in the tumor region. A significant correlation was found between Tl-201 uptake and tumor grade in chondrosarcoma (p = 0.002, r = 0.71). Only a few reports in literature have demonstrated false negative results in low-grade chondrosarcoma. CONCLUSION: Tl-201 uptake was related to tumor grade in chondrosarcoma. If there is a possibility of chondrosarcoma, Tl-201 scintigraphy should be reported with caution.

A patient with diffuse large B-cell non-Hodgkin's lymphoma and AA type amyloidosis.

AA-type amyloidosis is a consequence of a long-standing systemic inflammation and is not associated with a monoclonal protein or clonal bone marrow plasma cells. Proinflammatory cytokines such as interleukin (IL)1, IL-6, and tumor necrosis factor (TNF) stimulate the synthesis of serum amyloid A during inflammation. Although the association of non-Hodgkin's lymphoma (NHL) with AL-type amyloidosis is well known and patients with Hodgkin's lymphoma with AA amyloidosis have been described, AA-type amyloidosis with NHL is extremely infrequent. We report a case of amyloidosis associated with NHL that subsided during R-CHOP chemotherapy.

Selective loss of B-cell phenotype in lymphocyte predominant Hodgkin lymphoma.

The neoplastic Reed-Sternberg cells characteristic of classical Hodgkin's lymphoma (cHL) are of B-cell origin but they almost always show striking loss of a range of B-cell-associated molecules. In contrast, the neoplastic cells found in lymphocyte predominant Hodgkin's lymphoma (LPHL) (L&H cells) are traditionally thought of as possessing the full repertoire of features associated with germinal centre B cells (eg BCL-6 expression, 'ongoing' Ig gene mutation). In the present paper, we report an extensive phenotypic analysis of L&H cells which revealed down-regulation of a number of markers associated with the B-cell lineage (eg CD19, CD37) and with the germinal centre maturation stage (eg PAG, LCK). The promoter methylation status of three of these down-regulated genes (CD10, CD19, and LCK) was further studied in microdissected L&H cells, and this revealed that their promoters were unmethylated. In contrast, these genes showed promoter methylation in cell lines derived from CHL. Further investigation of the mechanisms responsible for the deregulation of these molecules in L&H cells may provide new insights into the genetic abnormalities underlying LPHL.

Prognostic significance of nuclear morphometry in superficial bladder cancer.

OBJECTIVE: To evaluate the significance of nuclear morphometry in predicting the clinical course in superficial (pTa and pT1) bladder cancer. STUDY DESIGN: The study included 73 patients with superficial transitional cell carcinoma of the bladder who were followed for a median of 21 months (range, 1-90). Nuclear morphometry was performed by a computer-assisted image analyzer system on hematoxylineosin-stained histologic sections and characterized by five nuclear variables: area, perimeter, major and minor diameter, and form factor. Patient charts and microscopic slides were reviewed to record tumor stage, grade and size. Tumor proliferative activity was assessed by immunohistochemical staining with Ki-67 antibody. RESULTS: None of the morphometric variables showed a significant relation to tumor progression and recurrence. Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher grade and proliferative activity. Mean nuclear area and minor diameter were associated with advanced stage. Of established prognostic factors, only histologic grade was significant in predicting progression. CONCLUSION: The results suggest that nuclear morphometry may be valuable in determining proliferative activity and may be well correlated with histologic grade in superficial bladder cancer. However, like many other potential prognostic factors, it seems to be unreliable in predicting clinical behavior.

Curschmann's spirals in cyst fluid associated with a teratoma of the ovary. A case report.

BACKGROUND: Curschmann's spirals, first described more than 100 years ago, are common in cytologic specimens from the respiratory tract and have also been observed in cervical smears, urine, and peritoneal and pleural effusions. No simple theory can explain the exact mode of spiral formation, which is presumed to be a complex physical and biochemical phenomenon. CASE: A 29-year-old woman, gravida 2, para 2, underwent right ovarian cyst excision after an abdominal ultrasound examination revealed a cystic mass of the right ovary. Histologically, the cyst was an immature cystic teratoma containing respiratory epithelium with mucous glands in the submucosa. Cytologic examination of the cyst fluid showed the presence of Curschmann's spirals. CONCLUSION: To the best of our knowledge, the formation of Curschmann's spirals associated with an immature cystic teratoma has not been previously reported. In this situation, the presence of spirals could be explained by formation from mucus normally found in that environment.

Tl-201 uptake in bone and soft tissue involvement of sarcoidosis.

The authors describe a 38-year-old man who was referred to the nuclear medicine department because of pain and swelling of his fingers in both hands. Tc-99m MDP and Tl-201 scans were performed to evaluate the lesions. A Tc-99m MDP bone scan showed hyperemia and increased uptake in the lesions. A Tl-201 scan showed marked uptake in both early and delayed images in the lesions of his fingers. Bone biopsy and histologic examination confirmed sarcoidosis. This case indicates that Tl-201 uptake can be seen in bone lesions resulting from sarcoidosis.

Hemophagocytic syndrome associated with inappropiate secretion of antidiuretic hormone in lymphoma and acute myeloblastic leukemia: report of two cases.

Hemophagocytic syndrome (HPS) is a rare clinicopathological disorder characterized by systemic proliferation of phagocytizing histiocytes associated with fever, cytopenias, lymphadenopathy, hepatosplenomegaly, and disseminated intravascular coagulopathy. We present the association of hemophagocytic syndrome associated with inappropriate secretion of antidiuretic hormone (SIADH) in two cases of hematological malignancies; anaplastic large cell lymphoma (ALCL) and acute myeloblastic leukemia (AML M4) In the patient with lymphoma, the diagnosis of lymphoma, HPS and SIADH were concurrent. In the patient with AML, HPS and SIADH were observed while the patient was in hematological remission. Thus it seems that patients with HPS may also carry a risk for the development of SIADH; the relationship with HPS and SIADH should be further investigated.

Stereologically estimated mean nuclear volume and histopathologic malignancy grading as predictors of disease extent in non-small cell lung carcinoma.

The aim of this study was to investigate the value of the architectural grade, cytologic atypia, mitotic counts and stereologically estimated mean nuclear volume in predicting the stage of disease in non-small cell lung carcinomas. Hematoxylin-Eosin-stained sections from 53 non-small cell lung carcinomas were evaluated in terms of the morphologic and morphometric features mentioned above. Mean nuclear volume was estimated stereologically. Operable and inoperable tumor stages were compared concerning the parameters examined. There was no significant difference between operable and inoperable tumor stages in terms of the architectural grade in both squamous cell carcinomas and adenocarcinomas, although we found a positive correlation between architectural grades and increasing stages in SCC. Significant differences were found concerning atypia, mitosis grades, and the score combining both variables (C2) when comparing operable with inoperable tumor stages in squamous cell carcinomas but not in adenocarcinomas (Chi square, p = 0.013, p = 0.008 and p = 0.008 for squamous cell carcinomas respectively). The mean nuclear volumes of tumor cells in both squamous cell carcinomas and adenocarcinomas showed statistically significant differences between operable and inoperable stages (p = 0.05 and 0.02 respectively). We conclude that an assessment of the proliferative activity and the degree of cell atypia, as well as an estimation of mean nuclear volume in conjunction with architectural grade, may contribute to predicting the extent of the disease and outcome, particularly in SCC. On the other hand, only mean nuclear volume appears to be a useful parameter for determining the course of the disease in adenocarcinomas.

Angiogenesis and p53 and H-ras mutations in pancreatic ductal adenocarcinoma.

OBJECTIVE: To evaluate the correlation of angiogenesis and p53 and H-ras mutations with prognostic factors and proliferative activity assessed with Ki-67 protein expression by studying archival tissues from 24 patients with primary pancreatic ductal adenocarcinoma. STUDY DESIGN: Vascular structures were labeled immunohistochemically using factor VIII-related antigen. Vascular surface density (VSD) and microvessel number (NVES) were assessed by stereology. The tissues were also analyzed with the immunohistochemical method for the expression of proteins, including p53, H-ras and Ki-67. RESULTS: Statistical analysis revealed that tumors with greater NVES and VSD values significantly correlated with occurrence of metastases, higher proliferative activity, poorer histologic differentiation and greater tumor size. p53 Mutations were found in 11 cases (45.8%). However, only three cases (12.5%), all negative for p53 mutations, showed H-ras mutations. p53 Mutation-positive tumors exhibited a statistically significant correlation with occurrence of metastases and higher proliferative activity, whereas H-ras mutations did not show such a correlation. CONCLUSION: Angiogenesis might have a role in predicting prognosis in pancreatic carcinomas, and p53 mutations might be acquired in later stages associated with metastatic progression and higher proliferative activity. Although H-ras mutations were rare in the present study, they might play a role in a different carcinogenic pathway excluding p53 mutations.

Locally recurrent paratesticular rhabdomyosarcoma treated with surgery and radiotherapy.

Paratesticular rhabdomyosarcoma is a highly malignant neoplasm and is exceedingly rare in adults. Thus, its biological behavior is unclear and there is no standard established treatment. The prognosis of recurrent paratesticular rhabdomyosarcoma is dismal in the elderly. Herein we describe a case of locally recurrent paratesticular rhabdomyosarcoma in a 68-year-old patient treated with surgery and radiotherapy.