Overexpression of FAK may be part of a mechanism for invasion and metastasis of thyroid cancer. Furthermore, the levels of p125FAK may serve as a marker of biologic behavior in this disease.

Using a PCR-based cloning technique, we have isolated a series of DNA fragments coding for tyrosine kinases that are expressed in a metastatic human colon tumor, and have subsequently analyzed their expression pattern at the protein level in human tumors. We identified both the alpha and the beta forms of the platelet-derived growth factor receptor (PDGFR), axl and 8 other genes, including 3 cytoplasmic tyrosine kinases. To study their expression in human colon cancer, we performed Western blots of matched sets of normal tissues and of carcinomas from the same patient. These revealed that the alpha-PDGFR migrates predominantly as a 200-kDa band in 8/8 normal tissues, and as a 170-kDa band in 17/17 malignant tissues, as well as in colonic polyps, suggesting that expression of an isoform of this receptor may be a marker for the progression of colon cancer. Additional studies showed that the Axl receptor tyrosine kinase was expressed at 10-fold higher levels in a peritoneal metastatic nodule than in other normal and malignant tissues. Immunohistochemistry revealed Axl over-expression specifically in the malignant cells of the tumor. This indicates that over-expression and possibly a differential processing event of tyrosine kinase receptors may be involved in colon cancer, and that they are potential markers for the progression of this disease.

The t(14;18) translocation is a common somatic mutation in non-Hodgkin's lymphoma (NHL) that is associated with bcl-2 activation and inhibition of apoptosis. We hypothesized that some risk factors might act specifically along t(14;18)-dependent pathways, leading to stronger associations with t(14;18)-positive than t(14;18)-negative non-Hodgkin's lymphoma. Archival biopsies from 182 non-Hodgkin's lymphoma cases included in a case-control study of men in Iowa and Minnesota (the Factors Affecting Rural Men, or FARM study) were assayed for t(14;18) using polymerase chain reaction amplification; 68 (37%) were t(14;18)-positive. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) for various agricultural risk factors and t(14;18)-positive and -negative cases of non-Hodgkin's lymphoma, based on polytomous logistic regression models fit using the expectation-maximization (EM) algorithm. T(14;18)-positive non-Hodgkin's lymphoma was associated with farming (OR 1.4, 95% CI = 0.9-2.3), dieldrin (OR 3.7, 95% CI = 1.9-7.0), toxaphene (OR 3.0, 95% CI = 1.5-6.1), lindane (OR 2.3, 95% CI = 1.3-3.9), atrazine (OR 1.7, 95% CI = 1.0-2.8), and fungicides (OR 1.8, 95% CI = 0.9-3.6), in marked contrast to null or negative associations for the same self-reported exposures and t(14;18)-negative non-Hodgkin's lymphoma. Causal relations between agricultural exposures and t(14;18)-positive non-Hodgkin's lymphoma are plausible, but associations should be confirmed in a larger study. Results suggest that non-Hodgkin's lymphoma classification based on the t(14;18) translocation is of value in etiologic research.

No abstract

Although carcinoma of the uterine endometrium is the most frequently diagnosed malignancy of the female reproductive tract, the molecular genetic features of this tumor have yet to be described in significant detail. Since mutations of the p53 tumor suppressor gene are the single most common genetic alteration found in human malignancies, we examined the hypothesis that p53 mutations occur in human endometrial carcinoma. Sequencing analysis of exons 5-8 revealed point mutations in 3 of 21 (14%) tumors; one mutation was an unusual single-base insertion at codons 176-177, resulting in a premature stop codon, whereas the other two were CGG----TGG transitions at codon 248. Two of these tumors showed reduction to homozygosity at the p53 allele, but one tumor apparently retained heterozygosity. These data indicate that p53 mutations occur in human endometrial carcinoma, although relatively infrequently, and that loss of the normal p53 allele does not necessarily occur with point mutation of the p53 gene in this tumor type.

No abstract

A monoclonal antibody prepared against estrogen receptor has been shown to be highly specific and sensitive for the detection and quantification of estrogen receptor in human breast lesions using immunohistochemical methods. A semiquantitative relationship has been shown between the intensity of staining and biochemical receptor analysis. To evaluate the usefulness of this technique in fine needle aspiration biopsies, 41 cases of breast cancer were studied. Nuclear localization of receptor antibody PAP complex was observed. Comparison of the immunocytochemical analysis of the aspiration cytologic specimens to the biochemical analysis of the excised tumor mass revealed a sensitivity and specificity of 80% and 89%, respectively. There was a significant semiquantitative correlation between the methods. These results extend the observation that antireceptor monoclonal antibody in immunohistochemical analysis is an effective tool in the evaluation of estrogen receptor content in human breast lesions and with careful specimen handling and proper controls may be extended to the evaluation of fine needle aspiration biopsies.

Accurate preoperative staging is important for proper selection of patients for radical retropubic prostatectomy. Preoperative staging by digital rectal examination, transrectal ultrasound, magnetic resonance imaging (MRI), Gleason grade and prostate specific antigen was compared to pathological stage for 25 patients who underwent radical retropubic prostatectomy. The predictive value for tumor confinement was 36% by rectal examination, 37% by ultrasound and 30% by MRI. The predictive value for extracapsular disease was 100% by rectal examination, 83% by ultrasound and 66% by MRI. Preoperative determinations of tumor volume by any modality did not correlate with pathological tumor volume. Digital rectal examination, ultrasound and MRI clinically understage the disease in most patients but they may be reliable to predict extracapsular disease.