The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p.

The JC12 monoclonal antibody recognizes a previously unknown nuclear protein that showed a restricted distribution in normal tonsil and was also overexpressed in a subset of diffuse large B-cell lymphomas. Using this reagent, we expression cloned cDNAs encoding its antigenic target and identified this protein as a novel putative transcription factor, FOXP1. The FOXP1 protein sequence contains predicted domains characteristic of transcription factors, including a winged helix DNA-binding motif, a second potential DNA-binding motif, a C(2)H(2) zinc finger, nuclear localization signals, coiled-coil regions, PEST sequences, and potential transactivation domains. The FOXP1 gene has been mapped to chromosome 3p14.1, a region that commonly shows loss of heterozygosity in a wide range of tumors and which is reported to contain a tumor suppressor gene(s). Using tissue arrays and immunohistochemistry, we demonstrate that both the FOXP1 mRNA and protein are widely expressed in normal tissues. The levels of FOXP1 mRNA were compared in paired normal and tumor tissues (from the same patient) using a tissue array containing cDNAs extracted from 68 samples taken from kidney, breast, prostate, uterus, ovary, cervix, colon, lung, stomach, rectum, small intestine, and from nine cancer cell lines. Differences in FOXP1 mRNA expression between normal and tumor samples were observed in 51% of cases. Most striking was the comparative loss of expression in 73% of colon tumors and comparative overexpression of FOXP1 mRNA in 75% of stomach tumors. Analysis of the FOXP1 mRNA expression in normal tissues (not taken from cancer patients) indicated that loss of FOXP1 expression may occur in some histologically normal tissues adjacent to tumors. Immunohistochemical analysis of FOXP1 protein expression was performed on 128 solid tumors, including 16 renal, 9 breast, 12 lung, 20 colon, 21 stomach, 10 head and neck, 35 prostate, and 5 pancreatic cases. Complete loss of expression, increased expression, and cytoplasmic mislocalization of the predominantly nuclear FOXP1 protein were frequently observed in neoplastic cells. Our study identifies FOXP1 as a new candidate tumor suppressor gene localized to the chromosome 3p14.1 region.

Immunohistochemical evaluation of estrogen and progesterone receptors in adenoid cystic carcinoma of salivary gland origin.

Adenoid cystic carcinoma (ACC) is a malignant tumor of salivary gland origin, which is characterized by a high rate of local recurrence and distant metastasis even after aggressive surgical treatment. In several studies using various immunohistochemical techniques, estrogen and progesterone receptor (ER and PgR) proteins in salivary gland ACC have been identified and the possible use of endocrine therapy as a treatment modality suggested. On this basis, 27 samples of formalin-fixed paraffin-embedded salivary gland ACC were immunohistochemically evaluated for the presence of ER and PgR. ER was not detected in any of the tumors and PgR was identified in only two cases. Thus, application of hormone therapy to salivary gland ACC is not supported by the results of the present study.

Prevalence of hypothyroidism and diabetes mellitus in elderly kibbutz members.

UNLABELLED: The aim of this study was to determine the prevalence of hypothyroidism and diabetes mellitus (DM) in elderly (aged 65-92 years) kibbutz members in Northern Israel. METHOD: The medical records of 1096 elderly (642 females and 454 males) residing in 11 kibbutzim were reviewed for data regarding thyroid function tests (TSH and FT4) and fasting blood glucose. Fasting blood glucose levels above 7.8 mmol/l was considered diagnostic for diabetes mellitus. RESULTS: The prevalence of hypothyroidism was 14% (9.7% in males and 18.2% in females) and that of DM was 11.5% (12.1% in males and 11.1% in females). In 74% of the diabetics the diagnosis was made after the age of 60 years. Distribution of treatment modalities in diabetics was as follows: diet only 42%. oral hypoglycemic agents 52% and Insulin 6%. Subclinical hypothyroidism (serum TSH levels above 4.5 mU/L with normal FT4 levels) was detected in 38% of all the hypothyroid subjects. CONCLUSION: The data suggest that diabetes mellitus and primary hypothyroidism are common disorders in elderly subjects. DM in the elderly can usually be handled with diet and oral hypoglycemic drugs. Since the clinical features of hypothyroidism in the elderly are often atypical, we suggest that elderly subjects should be screened for hypothyroidism.

[Watermelon stomach: a cause of chronic blood loss in the elderly].

Watermelon stomach, or gastric vascular ectasia, is a relatively new, distinct clinical entity. This rare vascular abnormality of the stomach causes severe chronic blood loss and iron-deficiency anemia, particularly in the elderly. Endoscopically it is characterized by longitudinal antral folds which contain visible vessels radiating from the pylorus, and resembling the dark stripes on the surface of some watermelons. This endoscopic picture may easily be misinterpreted as antral hemorrhagic gastritis. The specific histologic features which establish the diagnosis on endoscopic biopsy are dilation and thrombosis of mucosal capillaries and fibromuscular hyperplasia of the lamina propria. Associated diseases, including achlorhydria, pernicious anemia and chronic liver disease have been reported. We recently encountered 2 cases of watermelon stomach associated with pernicious anemia and hypothyroidism. This entity should be considered in the differential diagnosis of iron-deficiency anemia.

[Primary gastric tuberculosis].

Intestinal tuberculosis (TB) comprises 5% of all cases of TB and may be a major problem in immigrant communities, although the incidence of pulmonary TB is declining. Gastric TB is rare, constituting 0.1-2% of all cases of TB. Gastric TB usually develops secondary to other tuberculous lesions, most commonly pulmonary. On endoscopy antral infiltrative lesions are found. Primary gastric TB is very rare, only 8 cases having been reported in the English literature. We report a case of primary gastric TB in a 55-year-old woman who presented with abdominal pain and gastric outlet obstruction. The diagnosis was confirmed by endoscopic biopsies which showed granulomas, but no acid-fast bacilli. The Mantoux test was positive, acid-fast bacilli were found in the gastric juice, and a positive culture for TB was obtained on gastric lavage. There was an excellent response to antituberculous chemotherapy. With the relative rate of extra-pulmonary TB increasing, primary gastric TB should be taken into account in the differential diagnosis of infiltrative lesions of the antrum.

Exogastric neurilemmoma presenting as acute abdomen: role of computed tomography in diagnosis.

A case of subserosal gastric neurilemmoma is hereby presented. This reported case is unique in its clinical presentation including the appearance of acute abdomen and fever subsequent to unremarkable and uneventful upper gastrointestinal endoscopy. The tendency of neurilemmoma to cause mucosal ulceration with fistula formation probably led to this clinical presentation. The role of computed tomography in establishing diagnosis of exogastric tumor is emphasized.