Is the urokinase-type plasminogen activator system a reliable prognostic factor in gastric cancer?

AIM: The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohistochemically assessed uPA and PAI-1 in patients with gastric cancer. METHODS: This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. RESULTS: Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). CONCLUSIONS: Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.

Feasibility of sentinel node concept in gastric carcinoma: clinicopathological analysis of gastric cancer with solitary lymph node metastases.

BACKGROUND: The feasibility and diagnostic reliability of sentinel lymph node biopsy of gastric carcinoma are still unclear and controversial. PATIENTS AND METHODS: To assess the applicability of the sentinel node concept to gastric carcinoma, we retrospectively analyzed the location of metastatic lymph nodes in patients with only one or two lymph node metastases. RESULTS: A total of 135 patients, who underwent gastrectomy with D2 lymphadenectomy for primary gastric adenocarcinoma between 1997 and 2001, were enrolled in this study. An average of 39 lymph nodes were resected and analyzed for each patient. Of the 135 patients, 88 (65%) were subtyped as pN+ (with lymph node metastasis); of the latter, 15 cases (pT1-3; 17% of N+ cases) showed one or two lymph node metastases. In 14 (93%) of these patients, lymph nodes directly adjacent to the primary tumor were involved. Skip metastases were only seen in one patient with cardia carcinoma and lymph node involvement of compartment II (left gastric artery). CONCLUSION: In patients with gastric carcinoma, especially in early stage carcinoma, the phenomenon of skip metastasis is infrequent. Therefore, the sentinel node concept may be feasible in gastric cancer.

Tenascin expression in gastric cancer with special emphasis on the WHO-, Lauren-, and Goseki-classifications.

Ample evidence has been provided concerning the presence of tenascin in various histological subtypes of gastric cancer. However, conflict and discussion still persist regarding the correlation with different classification systems and prognostic impact. Therefore, we studied 203 adenocarcinomas of the stomach with special emphasis to the WHO-classification, Lauren's and Goseki's subtypes as well. The immunohistochemical ABC-method was applied using a monoclonal anti-human-tenascin antibody. 30% of all tumours showed a distinct staining reaction. Tubulo-papillary carcinomas (WHO) revealed a significantly stronger reactivity than signet-ring subtypes. Adenocarcinomas of intestinal type (Lauren) were significantly more positive than the diffuse types. Mucin-poor tumours (Goseki I+III) stained positive in a much higher degree compared to mucin-rich subtypes (Goseki II+IV). However, no correlation could been demonstrated regarding TNM-stage or prognosis.

Masaoka staging is of prognostic relevance in type B3 / C thymomas.

BACKGROUND: The purpose of this study was to correlate the Ki67 labelling index (LI) with the Masaoka classification and the new WHO-classification in type B3 / C thymomas. PATIENTS AND METHODS: Fourteen patients with type B3 / C thymomas were evaluated, and archived specimens were histologically reclassified according to Masaoka staging, the new WHO classification and the Ki-67 LI in a retrospective analysis. RESULTS: Four patients presented with Masaoka stage II disease (all WHO-type B3), 1 patient had stage III (WHO-type C), 6 stage IVa (3 WHO-type B3 and 3 WHO-type C), and another 3 patients stage IVb (all WHO-type C). The statistical analysis revealed a significant correlation between Masaoka staging and Ki-67 LI (II, III vs. IV; p = 0.007). As well, WHO-classification correlated significantly with Ki-67 LI (B3 vs. C; p = 0.015). Masaoka staging (II, III vs. IV) correlated significantly with survival status (p = 0.0237) in patients with type B3 / C thymoma whereas WHO-classification did not (p = 0.3266). Between survivors and non-survivors there was no statistically significant correlation concerning Ki-67 LI (p = 0.075). CONCLUSION: Our study indicated that the Masaoka staging system is of prognostic relevance in type B3 / C thymomas.

[Heterotopic gastric pancreas: a rare cause of abdominal complaints]. / Heterotopes Pankreasgewebe der Magenwand. Seltene Ursache abdominaler Beschwerden.

Heterotopic pancreas is an uncommon cause of gastrointestinal complaints such as epigastric pain, nausea, vomiting, and upper gastrointestinal bleeding. Despite the development of modern diagnostic procedures, it is still difficult to differentiate heterotopic pancreatic tissue from other benign or malignant gastric tumors. Local excision of the gastric wall is regarded as the diagnostic and therapeutic procedure of choice. We present two cases and an overview of the literature.

Apoptosis and expression of bcl-2 protein are inverse factors influencing tumour cell turnover in primary carcinoid tumours of the lung.

AIMS: This study evaluates potential regulating factors in primary pulmonary carcinoid tumours, 16 typical and four atypical samples, with special emphasis on apoptosis and the bcl-2 gene family. Furthermore, p53-related oncogenes were analysed in a search for associated biological parameters. METHODS AND RESULTS: The in-situ end-labelling technique (ISEL) was used to determine apoptotic cells, in addition to immunohistochemical methods, which were used to investigate the expression of the Ki67 antigen (avidinbiotin complex (ABC) method) and bcl-2, bcl-x, p53, p21/waf1, p27 and mdm-2 proteins (catalysed reporter deposition (CARD) technique). The incidence of apoptotic tumour cells was significantly enhanced in typical carcinoids. The bcl-2 protein was expressed to a higher degree in atypical carcinoids, which displayed a higher proliferative capacity as well. In contrast, bcl-x was observed predominantly in so-called typical carcinoids. The tumour cell turnover index was the most distinguishing parameter between both entities. All carcinoid tumours failed to show a staining for p53, p21/waf. p27 and mdm-2 proteins. CONCLUSIONS: The different biological behaviour of the carcinoid tumours under study seems to be influenced by the bcl-2 gene family preventing programmed cell death. We speculate that this results in a more aggressive course in atypical carcinoid tumours.

Prognostic impact of p21/waf1/cip1 in colorectal cancer.

In addition to the tumor suppressor gene p53, Cyclin Dependent Kinases (CDK) are well known to influence the cell cycle in normal human tissues and various neoplasias as well. The purpose of our present study was to evaluate the expression of the CDK-inhibitor p21/waf1/cip1 in colorectal cancer with special emphasis on the prognostic impact. Between 1985 and 1991, 294 patients (median age, 65 years) underwent surgical operative therapy for colorectal cancer. Formalin-fixed and paraffin-embedded tumor specimens were investigated. For immunohistochemistry the Catalysed Reporter Deposition (CARD) technique was performed. The survival probability was calculated and possible prognostic risk factors were tested using multivariate analysis. The p21/ waf1/cip1 staining pattern was positive in 197 (67%) specimens and negative in 97 (33%) samples. No significant correlation could been calculated between p21/waf1/cip1 expression and other variables such as age, sex, WHO-Classification, localisation, grading, TNM-classification or UICC-stage. Patients with a positive staining reaction had a significantly better survival (p < 0.0052). Moreover, p21/waf1/cip1 was shown to be an independent prognostic parameter by multivariate analysis (p < 0.022). In contrast with these findings, the p53 tumor status had no impact on survival. P21/ waf1/cip1 appears to be an independent prognostic parameter in colorectal cancer and is associated with a favorable survival. This feature may be related to a cell cycle arrest in the G1 phase induced by p21/waf1/cip1, resulting in lower tumor cell proliferative activity.