Isoform expression of CD44 adhesion molecules, Bcl-2, p53 and Ki-67 proteins in lung cancer.

CD44, belongs to the cell adhesion molecule family and is expressed on cell surfaces in several isoforms which are generated by alternative splicing of messenger RNA. These splice variants have been shown in several cancer cell types and are thought to be involved in tumor progression. The aim of the current study was to evaluate the expression of selected CD44 variants on lung cancer cells of various histology and to compare these with other markers of tumor spread. Surgical samples of primary lung carcinoma of various histology were subjected to alkaline phosphatase-anti-alkaline phosphatase complex immunohistochemistry using a panel of monoclonal antibodies: anti-CD44 v5, v6, v7/8, v10, anti-Ki-67, anti-Bcl-2 and anti-p53. Positive cells were scored in a semiquantitative way. The patients were subdivided into groups with and without metastases, as found during surgery. All CD44 variants tested could be demonstrated on lung cancer cells, but the incidence of particular isoforms varied, depending on lung cancer histology. In general, CD44 expression was highest in squamous cell tumors and lowest in anaplastic small cell carcinomas. Squamous cell cancers had high expression of v5 and v6 variants, while in anaplastic large cell and small cell carcinomas v10 was abundant. When Ki-67, Bcl-2 and p53 protein expression was compared to the incidence of CD44 variants, coincidence was found for v10 only. Most of the cases positive for v10 were also Ki-67 positive (p = 0.0146). In 12 cases with metastases, tumor cells had high v6 and Ki-67 expression, but these data were not significant compared to cases without metastases. Overall, these data suggest that v5 and v6 variants are of significance in squamous cell lung carcinoma, presumably in the promotion of metastasis, while in anaplastic small cell or large cell cancers only v10 expression seems to correlate with proteins associated with tumor growth and progression.

[Tumor escaping mechanisms present in microenvironment of laryngeal cancer]. / Mikrosrodowisko raka krtani--mechanizmy miejscowe wplywajace na ucieczke nowotworu spod nadzoru immunologicznego.

In tumor tissue obtained from a group of 21 patients treated surgically for laryngeal carcinoma, the expression of Fas, Fas-L, CD3, TCR zeta chain and Bcl-2 were estimated. It has been shown that tumor often express: Fas-L, Fas, Bcl-2, the molecules which may influence increased tumor survival. On the other hand lack of MHC class I antigen expression on tumor cells frequently has been observed. As it is known, such tumor cells can not be recognized by cytotoxic T lymphocytes. Frequently observed decreased expression of TCR zeta chain and high level of apoptosis among T cells present in tumor microenvironment seems to depend on direct interactions with molecules expressed by tumor. Understanding of these interactions may be of great importance in evaluation of tumor aggressiveness, patients follow up and the approach to treatment.

Extracellular matrix proteins and VLA integrins expression in the microenvironment of human lung carcinoma.

In order to gain an insight into interactions between human cancer and the surrounding host tissues, surgical samples of lung carcinoma of distinct histological types were examined for the expression of extracellular matrix (ECM) proteins and very late antigen (VLA) integrins, by means of a panel of monoclonal antibodies and immunohistochemistry of frozen tissue sections. It has been found that fibronectin (FN), tenascin (TN) and to a lesser degree collagen IV were abundant in the immediate vicinity of the tumor, but only TN penetrated tumor mass. FN isoforms were scarce or undetectable within the tumor area. The walls of blood vessels in the vicinity of the tumor showed increased an expression of collagen IV and laminin. The latter was occasionally absent within the basal membrane of cancer cells. The expression of EMC proteins was inversely proportional to the intensity of mononuclear tumor infiltrating cells (TIC). VLA integrins were present on both types of the cells: TIC and tumor cells. Percentage of positive TIC varied from 20% to 70%, depending on VLA integrin tested. VLA-3 was demonstrated on most of the cells of squamous carcinoma, but was almost absent on those of anaplastic small cell carcinoma one. In metastatic lymph node, VLA-4 was strongly expressed on tumor cells comparing to lymphoid ones. These data show that VLA integrins and their EMC ligands play apparently an important, but still obscure role in the interactions between lung carcinoma and its host.