The present paper describes the primary structure, glycosylation and tissue localization of fetal antigen 1 (FA1) isolated from second-trimester human amniotic fluid. FA1 is a single-chained, heterogeneous glycoprotein of 225 -262 amino acid residues. FA1 has six well conserved epidermalgrowth-factor motifs and contains up to ten O-glycosylation and N-glycosylation sites, six of which are differentially glycosylated. Alignment to the translated sequences of Mus. musculus dlk and human dlk revealed 86% and 99% identity, respectively, to a 259-amino-acid residue overlap, and this high similarity extends with minor corrections to the human adrenal-specific mRNA, pG2 as well. Immunohistochemical analysis demonstrated the presence of FA1 in 10 out of 14 lung tumors containing neuroendocrine elements, and in the placental villi where FA1 was exclusively seen in stromal cells in close contact to the vascular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the p cells within the islets of Langerhans.Our findings suggest that FA1 is synthesized as a membrane anchored protein and released into the circulation after enzymic cleavage, and that circulating FA1 represents the post-translationally modified gene product of human dlk which, in turn, is identical to human adrenal-specific mRNA pG2.The circulating form of fetal antigen 1 (FA1) was originally isolated from normal human amniotic fluid during the second trimester of pregnancy (Fay et al., 1988). The fetal origin of FA1 was suggested in accordance with the quantitative distribution in fetal and maternal compartments and immunohistochemical analysis (Fay et al., 1988;Tornehave et al., 1989). High concentrations of FA1 were found in secondtrimester amniotic fluid and in fetal serum, whereas the concentration in normal human serum was found to be approximately 20ng/mL which is 1000-times less than in secondtrimester fetal serum (Jensen, 1992). In preliminary-tissue localization studies using the indirect immunoperoxidase technique on fetal tissues (week 7), FA1 immunoreactivity was detected in the hepatocytes of the fetal liver (Tomehave et Abbreviations. FA1, fetal antigen 1 ; EGF, epidermal growth factor; PDMS, plasma-desorption mass spectrometry ; MALDI-MS, matrix-assisted laser-desorptionionisation mass spectrometry; BCG, Bacille, Calmette, GuLrin ; PPD, purified protein derivative; PEG, poly(ethy1ene glycol) ; FITC, fluoroscein isothiocyanate ; NSE, neuron-specific enolase.

Summary The prognostic role of the epidermal growth factor receptor (EGFR) and the related receptor p185HER-2 in lung cancer is as yet undefined. We investigated the immunohistochemical expression of EGFR (monoclonal antibody RI; Amersham) and pl85HER-2 (polyclonal antibody A485; Dako) in cryosections. A total of 186 unselected and systemically untreated patients with non-small-cell lung cancer (NSCLC) diagnosed and treated at Odense University Hospital, Denmark, were included. Median follow-up period was 66 months.EGFR and pl85HER-2 was highly expressed in 55% and 26% of cases respectively. Expression of EGFR was independent of pl85HER-2 expression. The expression of EGFR was higher in squamous cell carcinomas whereas the level of pl85HER-2 staining was higher in adenocarcinomas. Expression of either or both receptors was not correlated with age, histological grading, stage and prognosis. We conclude that immunohistochemical detection of these growth factor receptors failed to demonstrate a prognostic significance in patients operated on for NSCLC.

Summary Cytogenetic analysis of short-term cultures from seven pulmonary hamartomas revealed an abnormal karyotype in six of them. The most characteristic aberration was an exchange of material between 6p21 and 14q24, found in three tumours. Abnormalities of either 6p or 14q were seen in another two hamartomas. Other regions that were rearranged more than once were 12q (three times) and 17p (twice), sometimes in exchange with 6p or 14q and giving rise to complex derivative chromosomes. Only one tumour had aberrations that did not involve 6p, 12q, 14q, or 17p. These results -together with the data on three previously reported pulmonary hamartomas, two of which also had t(6;14) -show that recombinations between 6p2l and 14q24 are common, and hence probably pathogenetically important. The data support the view that these tumours are genuine neoplasms rather than developmental anomalies. The coexistence of a common 14q24 breakpoint in uterine leiomyomas and pulmonary hamartomas indicates that a gene important in the genesis of both tumours exists in this band.

Summary The prognostic role of epidermal growth factor receptor (EGFR)

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