The role of microvascularization and growth/adhesion-regulatory lectins in the prognosis of non-small cell lung cancer in stage II.

OBJECTIVE: To investigate the role of growth/adhesion-regulatory lectins in the prognosis of the stage II non-small cell lung carcinomas (NSCLCs) via quantitative lectinhistochemical examinations and measurement of microvascularization of the tumour. METHODS: In 94 radically operated lung cancer patients, stage II NSCLC was confirmed histologically (T1N1: 6, T2N1: 66, T3N0: 22). Immunohistochemical methods were applied to investigate the galectin-1, galectin-3, CL-16 and hyaluronic-acid-binding capacities of the tumours, and also the expression of galectin-1, -3 and heparin binding lectin. Sections were examined with the aid of qualitative (stained/not-stained) and syntactic structure analysis. The microvessels were detected by staining with anti-factor VIII antibodies. The findings were compared with the survival data. RESULTS: In the univariate survival examinations, the prognosis was poorer for the galectin-1 and -3-expressing tumours (p=0.014 and p=0.003) and in multivariate analysis for the galectin-3-expressing tumours (p=0.046, RR: 2.026). Correlations could be demonstrated between the survival and the distance between the tumour cell for the tumours binding galectin-3 (p=0.039, RR: 5.944) and expressing galectin-3 (p=0.041, RR: 3.335). An elevation of the volume fraction of microvessels was a sign of a poor prognosis (p=0.017, RR: 2.334), however the increase of surface fraction improves the survival (p=0.01, RR: 0.956). CONCLUSIONS: In stage II NSCLC, galectin-3 expression is indicative of a poor prognosis. In tumour expressing and binding galectin-3, the distance between the tumour cells is of prognostic significance. An increase in the microvessel volume fraction points to a poorer survival rate.

[Prognostic role of microvascularization in surgically treated lung cancer]. / A mikrovaszkularizáltság prognosztikai jelentôsége operált tüdôrák esetén.

OBJECTIVE: The aim of our study was the determination of microvascularization and its prognostic significance in lung cancer patients. METHODS: Histological sections were prepared from paraffin-embedded tissues removed from the peripheral part of the tumor of 450 radically operated non-small cell and small cell lung cancer patients. Immunohistochemical staining was performed with antibody against factor VIII-associated antigen. During computer imaging, the absolute and relative parameters of vascularization were determined, as was the density of tumor cells situated to the nearest neighboring vessels. The results were compared with TNM status, the cell type and survival. RESULTS: T2 and T4 tumors demonstrated an enhanced vascularization, however, except for the surface fraction, statistically significant difference was not found. The microvascularization parameters did not differ significantly between tumors with different N status. In small cell lung cancer cases, the vascularization was stronger than in non-small cell lung cancer cases, while cell density was lower, however, these differences did not prove statistically significant. The survival rate decreased significantly with the increasing tumor cell density in the interval of 0-20 microm. CONCLUSIONS: A clear connection could not be demonstrated between vascularization and the appearance of lymph node metastases. The density of tumor cells measured in the direct vicinity of vessels proved an important prognostic factor.

Prognostic significance of endogenous adhesion/growth-regulatory lectins in lung cancer.

OBJECTIVE: To determine the expression of endogenous adhesion/growth-regulatory lectins and their binding sites using labeled tissue lectins as well as the binding profile of hyaluronic acid as an approach to define new prognostic markers. METHODS: Sections of paraffin-embedded histological material of 481 lungs from lung tumor patients following radical lung excision processed by a routine immunohistochemical method (avidin-biotin labeling, DAB chromogen). Specific antibodies against galectins-1 and -3 and the heparin-binding lectin were tested. Staining by labeled galectins and hyaluronic acid was similarly visualized by a routine protocol. After semiquantitative assessment of staining, the results were compared with the pT and pN stages and the histological type. Survival was calculated by univariate and multivariate methods. RESULTS: Binding of galectin-1 and its expression tended to increase, whereas the parameters for galectin-3 decreased in advanced pT and pN stages at a statistically significant level. The number of positive cases was considerably smaller among the cases with small cell lung cancer than in the group with non-small-cell lung cancer, among which adenocarcinomas figured prominently with the exception of galectin-1 expression. Kaplan-Meier computations revealed that the survival rate of patients with galectin-3-binding or galectin-1-expressing tumors was significantly poorer than that of the negative cases. In the multivariate calculations of survival lymph node metastases (p < 0.0001), histological type (p = 0.003), galectin-3-binding capacity (p = 0.01), galectin-3 expression (p = 0.03) and pT status (p = 0.003) proved to be independent prognostic factors, not correlated with the pN stage. CONCLUSION: The expression and the capacity to bind the adhesion/growth regulatory galectin-3 is defined as an unfavorable prognostic factor not correlated with the pTN stage.

Prognostic significance of microvascularization in cases of operated lung cancer.

OBJECTIVE: Measurement of microvascularization and determination of its prognostic significance in cases of lung cancer. METHODS: Section prepared from histological material from 432 radically operated non-small cell lung cancer patients were stained with antibodies against factor VIII-associated antigen. During computer imaging, the absolute and relative parameters of the vascularization were determined, as was the density of tumour cells situated in the vicinity of the vessels. The results were compared with the TNM status, the cell type and the survival. RESULTS: Each parameter demonstrated an enhanced vascularization in classifications T2 and T4, but only the surface fraction, the mean vascular circumference and the mean vascular area displayed a significant change. The microvascularization parameters did not differ significantly between with different N status, however, the cell density progressively increased in the areas close to the vessels in advanced pN classifications. Elevation of the tumour cell density within 20 microm distance of the vessels was accompanied by a significantly poorer survival rate. The density of tumour cells within 20 microm region was the second strongest prognostic factor after the N status. CONCLUSIONS: More advanced tumour classifications grow with enhanced vascularization. A clear-cut connection cannot be demonstrated between the vascularization and appearance of lymph node metastases. The density of tumour cells measured in the direct vicinity of vessels is an important prognostic factor.

Vascular diffusion density and survival of patients with primary lung carcinomas.

AIM: To investigate the clinical significance of tumour vascularisation in operated lung cancer patients. MATERIALS AND METHODS: Histological slides obtained from 498 patients with potentially curative operated lung carcinomas in two different institutions of thoracic surgery were immunohistochemically stained with an anti-CD34 antibody and subjected to quantitative image analysis. Syntactic structure analysis measured the absolute and relative features of vessels, including the numerical tumour cells densities relative to their nearest neighbouring vessel. These data are associated with tumour volume, post-surgical TNM stage, and each patient's survival. RESULTS: The clinical data, including sex distribution, age of patients, pTNM stages and survival, did not differ between the two institutions. The tumour vascularisation (volume fraction, Vv) amounted to 7% in lung carcinomas, was independent from cell type and increased in advanced tumour stages (pT4, pN3). Advanced tumour stages presented with a higher numerical vascular density and with maintained minimum diameter and circumference of vessels. Each patient's survival was closely associated with the pN stage, tumour volume, cell type and numerical density of tumour cells within a distance less than 20 micro m from the nearest neighbouring vessel due to multivariate statistical analysis. CONCLUSION: Vascularisation of lung tumours becomes altered in advanced tumour stages. Of prognostic significance is the distribution of tumour cells in relation to the nearest neighbouring vessel only.