Expression of Her2/neu oncogene product p185 in correlation to clinicopathological and prognostic factors of gastric carcinoma.

The expression of the Her2/neu gene product p185 was retrospectively analyzed in 58 patients with gastric carcinoma. The results were correlated to various clinicopathological and prognostic factors. Positive membrane staining for p185 could be detected in 38% of the patients (22/58). Membrane staining was significantly greater in well and moderately differentiated tumors of the intestinal type when compared with poorly differentiated lesions and carcinomas of the diffuse type (P less than 0.01). Positive membrane staining did not correlate with site and tumor stage, but T1 lesions had less membrane staining than more advanced primary tumors. Overall survival showed no difference between p185-positive and negative cases. Multivariate analysis defined a subgroup of curatively resected patients with stage III and IV disease that had a statistically significant poorer survival when p185 was overexpressed (P = 0.005). Overexpression of the Her2/neu product p185 appears to be associated with intestinal-type gastric carcinoma and may help in identifying a subset of patients at increased risk for shorter survival.

Lymphadenectomy in gastric carcinoma. A prospective and prognostic study.

In 193 gastric resections for adenocarcinoma, lymphadenectomy was prospectively evaluated to quantify the number of lymph nodes and to identify prognostic factors. Overall, 7112 nodes (median, 36.8 per patient) were resected with 27.2% showing metastases. Most nodes were found in the perigastric region. The histologic type and site of the tumor did not influence the number of invaded nodes, but tumor stage and quality of the resection (curative/palliative) did. By multivariate analysis the tumor stage, curative vs palliative resections, and the number of metastatic lymph nodes in curative resections were independent prognostic factors. Patients with less than six metastatic nodes showed a survival not significantly different from that of patients with normal nodes. These patients may be well treated by surgery alone, but the other patients may require multimodal therapy to improve their prognosis.

Amplification of HER-2/neu gene in human gastric adenocarcinomas: correlation with primary site.

Adenocarcinomas of the proximal stomach including the gastroesophageal junction are extremely virulent cancers which are increasing rapidly in incidence. Stage-for-stage proximal gastric cancers have a worse prognosis than do tumors of the body or antrum of the stomach. To further explore biological differences based on site, we studied 80 patients with locally advanced primary tumours of the proximal (n = 40) and distal stomach (n = 40) for amplification of the HER-2/neu proto-oncogene. None of 40 patients with proximal lesions had overexpression of HER-2/neu, whereas four of 40 (10%) distal adenocarcinomas had a 16-24-fold gene amplification (P = 0.04). In the adenocarcinomas from two patients, gene rearrangements were found in addition to amplification. HER-2/neu gene product p185 over-expression was found only in the amplified cases. All four patients with distal tumors and amplification had rapid progression of disease (median survival: 4.3 months). While it is unclear why HER-2/neu amplification is seen only in distal tumors, these data further support the hypothesis that biological differences between proximal and distal lesions are present. As is the case for other tumours, HER-2/neu amplification is associated with a poor prognosis for the individual patient.

Surgical treatment of gastric carcinoma: a retrospective analysis with special regard to the value of total gastrectomy as the operation of choice.

The surgical treatment of gastric carcinoma has been under discussion for many years with regard to the extent of surgical radicality, particularly in terms of total gastrectomy as the operation of choice. The main arguments against this procedure were high postoperative morbidity and mortality as well as poor long-term results, but objective data are not available at this time. Between 1968 and 1987, 1135 resections for gastric carcinomas were performed (714 total, 313 distal subtotal and 108 proximal gastrectomies). During different time periods the incidence of total gastrectomies as a proportion of all resections increased up to 81%. With increased experience the postoperative mortality following total gastrectomy fell to 2%. In this retrospective study no significant differences in the 5-year survival rates between distal subtotal and total gastrectomies could be obtained. However, exact definitions of histopathological features as well as data of epidemiological studies are able to describe more accurately the number of subtotal and total gastrectomies. These characteristics serve as a first step for prospective trials to define the extent of surgical radicality necessary from the oncological point of view with the aim of improving the long-term prognosis of patients with gastric carcinoma individually.