Μελέτη της πλοειδίας του DNA σε επιχρίσματα εντυπωμάτων κακοήθων νεοπλασμάτων του πνεύμονα και συσχέτιση με διάφορες κλινικοπαθολογοανατομικές παραμέτρους και την πρόγνωση

Abstract

Introduction: Lung cancer is the leading cause of death from neoplasia worldwide, accounting for 17.8% of all cancer deaths. It is usually diagnosed in advanced stages and most primary lung cancers are non-small cell lung cancers. The most accepted predictive factors are histologic stage, grade, lymph node metastasis and tumor size. Current research aims to evaluate new prognostic parameters, such as DNA ploidy, and transmembrane proteins E-cadherin and β-catenin. Objective: To evaluate, in imprints of resected non-small cell lung cancer, the relationship between DNA ploidy and E- cadherin / β-catenin expression with classical prognostic factors. Also, study the average DNA content in cancer cells in relation with E- cadherin / β-catenin expression. Materials and Methods: A total of 45 smears from patients (28 squamous cell carcinomas and 17 adenocarcinomas) who underwent surgical treatment for non-small cell lung cancer were studied. Imprints were stained with Papanicolaou and Giemsa cytology procedures for diagnosis and for evaluating and existence of cancer cells. Imprints were also stained with Theonin-Feulgen procedure in order to be used for image analysis and immunocytochemistry procedure for evaluating E- cadherin / β-catenin expression. Subsequently image analysis algorithms were used for (i) measuring the morphometric nucleus parameters (perimeter, area, diameter, roundness, aspect ratio) and (ii) measurement of DNA quantity (DNA index) and the generation of ploidy histograms in order to classify imprints to diploid and aneuploid. Results: Thirty-two (71.1%) of tumors were classified as aneuploid. E-cadherin positive expression was observed in 18 (40%) and β-catenin in 21 (46.7%) of the tumors. DNA ploidy was correlated only with differentiation (ρ2=10.778, p=0.005). From morphometric parameters nucleus area was significantly higher for poorly differentiated tumors (F=4.562, p=0.016). E- cadherin and β-catenin expression correlated with grade (ρ2=23.093, p<0.0001 and ρ2=18.975, p<0.0001 respectively) and lymphnode metastasis (ρ2=8.522, p=0.004 and ρ2=5.658, p=0.017 respectively). The mean DNA index was higher for tumors with negative expression of E- cadherin / β-catenin (t=2.064, p=0.045 and t=2,324, p=0.025 respectively). Conclusion: Poorly and medium differentiated tumors have a higher probability to be aneuploid. DNA ploidy is probably an epiphenomenon rather than a primary event in 136 NSCLC and is an independent prognostic factor. E-Cadherin, β-Catenin strongly expression was expressed mainly in well differentiated tumors that maintain cell adhesiveness and were less invasive. On the contrary their expression was reduced in poorly differentiated tumors which have lost their intercellular adhesion and demonstrate a strong invasive behavior. The results of the present study indicate that reduced expression of E- Cadherin and β-Catenin are significant factors in predicting positive nodal status and poorly differentiated tumors in NSCLC. Aneuploid tumors can also predict poorly differentiated tumors. Analyzing the DNA ploidy and E- Cadherin, β-Catenin expression pattern are very useful factors, combined with other clinicopathologic parameters.