KIT expression in fetal, normal adult, and neoplastic renal tissues

Background: KIT is a transmembrane tyrosine kinase receptor, expressed in high amounts in various normal cells. In addition, c-kit mutation or activation is a major pathogenetic event in certain tumours (such as gastrointestinal stromal tumours). There are only limited data in the literature on the expression of KIT in normal and neoplastic renal tissues. Aims: To investigate KIT expression in normal and neoplastic renal tissues. Methods: KIT expression was evaluated by means of immunohistochemistry in paraffin wax embedded sections from 67 tissue samples. Results: Eight of eight fetal kidneys, and 10 of 10 normal adult kidneys revealed cytoplasmic staining of renal tubules. The three cases of renal dysplasia studied expressed KIT in their normal and aberrant tubules. Two of 13 conventional renal cell carcinomas (RCCs), two of seven papillary type RCCs, four of seven chromophobe type RCCs, none of six nephroblastomas, seven of seven oncocytomas, two of two mesoblastic nephromas, and two of four angiomyolipomas were positive. Conclusion: KIT is expressed in normal fetal and adult renal tubules, and in a subset of renal tumours. The expression of KIT in these renal tumours may prove to have diagnostic relevance and/or therapeutic implications

Immunophenotypic Evaluation of DNA Mismatch Repair Markers in 2 Cases of Synchronous Histomorphologically Distinct Gastric Adenocarcinomas With Gastrointestinal Stromal Tumors of the Proximal Small Bowel

Objectives: To assess the prognostic value of combined mismatch DNA repair (MMR) phenotyping in 2 synchronous histomorphologically distinct gastric adenocarcinomas (GADCs), each accompanied by gastrointestinal stromal tumors (GISTs) of the proximal small bowel. Summary Background Data: A 72-year-old female and a 55-year-old male patient were submitted to partial and total gastrectomy, respectively, with synchronous resection of a GIST in the proximal small bowel. The 2 patients attained contrasting survival outcomes. The female survives disease-free 20 months after surgery having received no chemotherapy. The male who received adjuvant chemotherapy developed metastases in liver and lung, and died 18 months after surgery. Methods: We phenotype MSH2 and MLH1 protein expression in tumor relative to matched normal tissue by immunohistochemistry. Results: Immunohistochemistry analysis revealed different combined MMR phenotypes for the 2 histomorhologically distinct GADCs and similar for both GISTs studied. Conclusions: Good and bad prognosis for disease-free survival of patients based on reduced and elevated combined MMR phenotypic expression of the 2 histomorphologically distinct GADCs, could be explained by disease-associated emergence of genomic MMR alterations in the tumor. The impact of synchronous GISTs with common intermediate MMR phenotypes on patient survival is rather incidental and secondary to predominating GADCs

Estradiol and leptin as conditional prognostic IVF markers

We studied the concentration of serum estradiol and serum and follicular fluid leptin in 200 women undergoing their first in vitro fertilization with embryo transfer (IVF-ET) program at the time of human chorionic gonadotrophin administration and oocyte retrieval, in an attempt to assess their concerted role on embryo quality and the prognosis of IVF outcome. Low serum (46.49 +/- 8.4 ng/ml) and follicular fluid (52 +/- 9.8 ng/ml) leptin levels were associated with a high number of 'good-quality' embryos (73.6%) and high implantation (11.2%) and pregnancy (35.8%) rates and were observed in women with normal peak estradiol levels of between 1000 and 2000 pg/ml. It appears that leptin and estradiol interact coordinately in a concentration-dependent manner to control IVF outcome. Further studies will be required to substantiate and clarify the mechanism of proposed conditional interaction between the two hormonal systems

Role of Hyperglycemia in Isogeneic Islet Transplantation: An Experimental Animal Study

Objective: Study the role of hyperglycemia-induced beta cell loss on grafted islet destruction. Design: Male inbred rats were made diabetic by streptozotocin administration and used as islet donors and/or isograft recipients to probe directly the role of hyperglycemia as an important determinant of transplanted islet fate, following exclusion of immune-related causes of islet graft destruction like allograft immunity and disease recurrence. Results: Our studies showed that: a) Hyperglycemia destroyed islet but not pituitary isografts and b) Tight control of normoglycemia by sufficient islet mass engraftment prevented graft damage. Conclusion: While sustained hyperglycemia caused destruction of transplanted islet isografts, induction of normoglycemia by transplantation of sufficient islet mass to diabetic recipients had a beneficial long term effect on their functional engraftment

The Fat Content of Small Primary Breast Cancer Interferes with Radiofrequency-Induced Thermal Ablation

Background: Radiofrequency (RF) thermal ablation is a minimally invasive technique of local mass elimination with variable efficiency. Methods: Ten patients with small primary breast cancer diagnosed preoperatively by core needle biopsy were ablated percutaneously by an RF (Radionics Cool-tip) device operating on impedance control mode. The percent fat-containing area was calculated in each slide of a total of 47 slides introduced to IQ materials software image analysis. Results: Seven of 10 tumors with tumor diameter less than 2.8 cm and fat content less than 12.47% were totally ablated ( score 3). One of 10 with 3 cm tumor diameter and 5.45% fat content showed an intermediate degree of ablated tissue ( score 2), and the last 2 with 2 cm and 2.2 cm tumor diameter and more than 19.74% tumor fat content were minimally ablated ( score 1). Our present exploratory study on 10 patients suggests dependence of the degree of thermal damage on tumor fat content. Conclusions: We conclude that the fat content of small primary breast cancer could serve as a 'heat sink' and should be considered as a preventing factor of complete local tumor destruction by RF thermal ablation. Copyright (c) 2008 S. Karger AG, Base

Estradiol and leptin as conditional prognostic IVF markers

We studied the concentration of serum estradiol and serum and follicular fluid leptin in 200 women undergoing their first in vitro fertilization with embryo transfer (IVF-ET) program at the time of human chorionic gonadotrophin administration and oocyte retrieval, in an attempt to assess their concerted role on embryo quality and the prognosis of IVF outcome. Low serum (46.49 +/- 8.4 ng/ml) and follicular fluid (52 +/- 9.8 ng/ml) leptin levels were associated with a high number of ‘good-quality’ embryos (73.6%) and high implantation (11.2%) and pregnancy (35.8%) rates and were observed in women with normal peak estradiol levels of between 1000 and 2000 pg/ml. It appears that leptin and estradiol interact coordinately in a concentration-dependent manner to control IVF outcome. Further studies will be required to substantiate and clarify the mechanism of proposed conditional interaction between the two hormonal systems

Comparing normal primary endocervical adenoepithelial cells to uninfected and influenza B virus infected human cervical adenocarcinoma HeLa cells

Human adenocarcinoma HeLa cells surviving infection with low (10(-9) units), medium (10(-6) units), and high (10(-2) units) influenza B titers were compared to their uninfected precursors and to normal endocervical adenoepithelial and metaplastic cells using Papanikolaou-staining method and immunocytochemistry. Normal primary endocervical and infected HeLa cells surviving infection shared similar morphologic, phenotypic, and divisional patterns that differed drastically from those of uninfected HeLa cells. The number of infected hosts surviving 6-7 days of viral exposure did not change during 3-week follow-up period, and their cyclin E levels suggested that they had been arrested to the G1 phase of the cell cycle by viral stress. Our findings suggest that in addition to apoptosis, nononcogenic viral stress activated the expression of endocervical metaplastic-like motifs in surviving hosts. A mechanism of cell response to nononcogenic viral stress was proposed to explain these findings. We conclude that nononcogenic respiratory viruses specifically target and eliminate abnormal cells ectopically overexpressing appropriate receptors and may complement current treatments of cervical cancer

Sequence-based genotyping HPV L1 DNA and RNA transcripts in clinical specimens

We developed a direct sequence-based genotyping method to detect single and multiple HPV L1 DNA and RNA types in genital and dermatological specimens. Our method couples PCR amplification of a highly conserved HPV L1 segment using a broad spectrum-generic primer cocktail mix with automated sequencing of amplified PCR products, followed by GenBank sorting of sequencing data. We genotyped 5 skin and 30 cervical HPV DNA-positive specimens using this method and established its first experimentally derived working cutoff value with the aid of commercial hybridization-based techniques. We suggest that sequence-based genotyping of appropriately amplified DNA and RNA products may serve as a primary HPV detection method in dermatological specimens. It can be applied as an all-purpose genotyping method for rare HPV types not detectable by commercial hybridization-based techniques and for sorting multiple HPV infections by order of prevalence. (C) 2009 Elsevier GmbH. All rights reserved