Expression and activation of erbB-2 and epidermal growth factor receptor in lung adenocarcinomas.

ErbB-2 and EGFR (epidermal growth factor receptor) are expressed in lung adenocarcinomas and associated with a poor prognosis. Immunocytochemical analysis revealed erbB-2 and EGFR coexperession as a characteristic feature of most lung adenocarcinomas, and at levels of receptor expression present in bronchial epithelial cells. In primary lung tumours and cell lines, erbB-2 detected using Western blot analysis demonstrated low-level phosphotyrosine staining of the 185 kDa band, as compared with breast cancer cell lines. A549 and A427 lung adenocarcinoma cells treated with neu differentiation factor (NDF) showed increased erbB-2 phosphotyrosine staining, but to a much lesser extent than breast cancer cells. The lung cells were examined for expression of the potential autocrine growth factors NDF and transforming growth factor alpha (TGF-alpha) by Northern blot analysis. Both NDF and TFG-alpha mRNA were abundantly expressed in the A549 cells. NDF mRNA was highest during active cell proliferation and decreased in confluent cells or after treatment with the growth-inhibitory steroid dexamethasone. Primary tumours and cell lines expressed EGFR, showing higher basal level phosphotyrosine staining than erbB-2. Treatment with NDF and EGF (epidermal growth factor) stimulated cell growth, and in A549 cells the presence of both factors provided an additive increase in cell growth. The growth stimulus that ligand-activated erbB-2 and EGFR provides to lung adenocarcinoma cells may establish a background of continued cell proliferation over which other critical transforming events may occur.

E-cadherin expression in primary and metastatic thoracic neoplasms and in Barrett's oesophagus.

Reduced expression of E-cadherin, a Ca(2+)-dependent cell adhesion molecule present in normal epithelium, has been associated with invasive and metastatic cancer. Immunohistochemistry was used in examining the relationship between E-cadherin expression and stage in 59 oesophageal and 52 lung cancers. Advanced-stage oesophageal cancers were associated with both reduced and disorganised E-cadherin expression (P < 0.01). Advanced-stage lung adenocarcinomas generally exhibited disorganised or reduced E-cadherin expression, but no statistical association between expression pattern and stage was found (P > 0.05). No differences in stage were seen between tumours with reduced or disorganised E-cadherin expression. Altered E-cadherin expression was detected in dysplastic, non-invasive Barrett's oesophagus. Importantly, high-level E-cadherin expression was detected in 17 of 17 lymph nodes containing metastatic cancer. E-cadherin mRNA expression was decreased in tumours with reduced protein expression, but not in tumours with disorganised expression. Expression of alpha-catenin mRNA, an E-cadherin-associated protein, was detected in tissues with altered E-cadherin protein expression. Reduced and disorganised expression of E-cadherin appear to be related to transcriptional and post-translational events respectively, and both appear to represent altered cell adhesion associated with invasion and metastasis in thoracic neoplasms.

Colloid oncotic pressure and body water dynamics in septic and injured patients.

Colloid oncotic pressure (COP) and fluid shifts were studied in 43 septic (SS) patients and 33 injured (HS) patients (ISS = 48.2). During maximal postresuscitation fluid retention, plasma volume (PV/RISA), red cell volume (RBC/51Cr), inulin space (ECF), and COP were measured. Interstitial space (IFS), PV/IFS ratio, and correlation coefficients (r) were calculated. A subgroup of 22 SS patients and 22 HS patients of equal study weight were also compared. Septic patients had greater IFS expansion (17.6 L vs. 11.5 L) than HS patients who, by inference, had more intracellular expansion. Expansion of IFS in SS patients correlated (r = -0.76, p less than 0.02) with reduced plasma COP; this was not seen in HS patients (r = -0.09, p less than 0.35). In contrast, plasma COP correlated (r = 0.72, p less than 0.001) with PV/RISA in HS patients but not in SS patients (r = 0.09, p greater than 0.35). We conclude: (1) SS patients with greater IFS expansion that correlates with reduced plasma COP likely have increased capillary permeability; and (2) HS patients with less IFS expansion that does not correlate with reduced plasma COP likely have maintained capillary permeability with altered IFS matrix configuration causing reduced protein exclusion.