High frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in advanced breast tumors associated with aggressiveness of the tumor.

Background: The product of Wilms' tumor suppressor gene (WT1), a nuclear transcription factor, regulates the expression of the insulin-like growth factor (IGF) and transforming growth factor (TGF) systems, both of which are implicated in breast tumorigenesis and are known to facilitate angiogenesis. In the present study, WT1 allelic integrity was examined by Loss of Heterozygosity (LOH) studies in infiltrating breast carcinoma (n=60), ductal carcinoma in situ (DCIS) (n=10) and benign breast disease (n=5) patients, to determine its possible association with tumor progression. Methods: LOH at the WT1 locus (11p13) as determined by PCR-RFLP for Hinf1 restriction site and was subsequently examined for its association with intratumoral expression of various growth factors i.e. TGF-β1, IGF-II, IGF-1R and angiogenesis (VEGF and Intratumoral micro-vessel density) in breast carcinoma. Results: Six of 22 (27.2%) genetically heterozygous of infiltrating breast carcinoma and 1 of 4 DCIS cases showed loss of one allele at WT1 locus. Histologically, the tumors with LOH at WT1 were Intraductal carcinoma (IDC) and were of grade II and III. There was no correlation in the appearance of LOH at WT1 locus with age, tumor stage, menopausal status, chemotherapy status and lymph node metastasis. The expression of factor IGF-II and its receptor, IGF-1R was significantly higher in carcinoma having LOH at WT1 locus. A positive correlation was observed between the TGF-β1, VEGF expression and IMD scores in infiltrating carcinoma. Conclusions: The current study indicates that the high frequency of loss of allelic integrity at Wilms' tumor suppressor gene-1 locus in high-graded breast tumors is associated with aggressiveness of the tumor.

Clinical significance of insulin-like growth factor-1 receptor expression in stage I non-small-cell lung cancer: immunohistochemical analysis

BACKGROUND/AIMS: The insulin-like growth factor (IGF) system has been implicated in tumor growth, invasion, and metastasis. However, reports on the IGF-1 receptor (IGF-1R) based on radioimmunoassays are conflicting, and its prognostic implications in non-small-cell lung cancer (NSCLC) are still controversial. METHODS: Seventy-one paraffin-embedded tissue sections from stage I NSCLC patients were stained using a mouse monoclonal antibody against human IGF-1R. RESULTS: The intensity and frequency of IGF-1R expression on the membrane and cytoplasm of cancer cells was evaluated and scored using a semiquantitative system. IGF-1R expression was detected in nine of 71 (12.7%) cases. No significant relationship was found between clinical/histopathological parameters and IGF-1R expression. None of the patients whose tumor expressed IGF-1R had experienced distant metastasis or cancer-related death, although the difference did not reach statistical significance. CONCLUSIONS: We conclude that IGF-1R expression may not be a major prognostic factor for stage I NSCLC.

Deficiencia del receptor de hormona de crecimiento "Síndrome de Laron": descripción de un caso / Growth Hormone Receptor Deficiency \"Laron's Syndrome\": description of a case

Se presenta el caso de un paciente portador del Síndrome de Laron con todas las características clínicas del mismo: baja talla, frente prominente, puente nasal chato, escleróticas azules, desproporción cráneo facial con rostro pequeño, micrognatía, proporciones corporales normales, manos y pies pequeños. Los niveles elevados de hormona de crecimiento; descendidos de somatomedina (IGF1) y la respuesta al test de generación de IGF1 confirmaron bioquímicamente la patología. Dado el escaso número de pacientes con Síndrome de Laron informados se realiza esta publicación.