Expression of matrix metalloproteinase-9 in the neoplastic and interstitial inflammatory infiltrate cells in the different histopathological types of esophageal cancer.

Metalloproteinase-9 (MMP-9) is the proteolytic enzyme degrading type IV collagen, and plays important role in the invasiveness and metastatic potential of tumor cells. The aim of the current study was to compare the association between the intensity of MMP-9 expression in neoplastic cells and in the interstitial inflammatory infiltrate cells in esophageal cancer with clinicopathological features of esophageal cancer (EC) and in different histopatological types of EC, e.g. adenocarcinoma and esophageal squamous cell carcinoma. The study included 32 EC patients, 17 cases of squamous cell carcinoma and 15 cases of adenocarcinoma, verified histopatologically. The presence of MMP-9 in cancer tissue was investigated by immunohistochemistry on formalin-fixed, wax-embedded sections of esophageal cancers. The light microscopy was used to evaluate the expression of metalloproteinase-9 in cancer cells and in inflammatory infiltrate in the neoplastic interstitium in semi-quantitative scale. The expression of MMP-9 in cancer cells was positive in 81% of cases whereas in inflammatory cells - in 75% and increased with tumor stage, depth of tumor invasion (T factor) and lymph node metastases (N factor). In squamous cell cancer the MMP-9 expression in cancer cells and in inflammatory infiltrate was higher than those in adenocarcinoma. Mean value of MMP-9 expression in inflammatory cells was higher in early stages of EC, whereas mean expression of this enzyme in cancer cells increased with tumor stage. In conclusion, this is the first study comparing the expression of metalloproteinase-9 in cancer and inflamatory infiltrate cells in different histopatological types of esophageal cancer. We proved the synthesis of MMP-9 by cancer cells as well as by inflammatory cells and its correlation with tumor stage, tumor size, depth of tumor invasion and lymph node metastases. The results suggest the role of MMP-9 in esophageal tumorigenesis, although this issue requires further investigations

Posttranslational p53 phosphorylation in non small cell lung cancer cells after radio/chemotherapy

Wstęp: Jednym z najważniejszych regulatorów cyklu komórkowego i apoptozy jest białko p53. Wiele czynników zmienia ekspresję tego białka i modyfikuje jego funkcje. Celem badań autorów było określenie stabilności i wybranych potranslacyjnych modyfikacji białka p53 w przebiegu terapii raka płuca. Materiał i metody: Oceniano zmiany ilości markera uszkodzenia DNA - poli-ADP-rybozy, ploidię DNA, ekspresję antygenu proliferacyjnego Ki-67, ekspresję natywnego i zmutowanego p53 oraz intensywność reakcji fosforylacji wybranych reszt serynowych tego białka, C-końcowej Ser392 i N-końcowych Ser15 i Ser20 w próbkach pobranych w trakcie bronchoskopii chorych na nawrotowego niedrobnokomórkowego raka płuca przed radio- i chemioterapią i po niej. Badania objęły 23 pacjentów będących po zabiegu chirurgicznym w stadiach I-IIIA.Wyniki: Terapia obniżyła liczbę komórek będących w fazie G2/M, ale zwiększyła frakcję komórek w fazie S o około 50%. Zwiększyła także ekspresję białka p53 oraz ilość białka fosforylowanego w pozycjach Ser392 i Ser20, a zmiany te korelowały ze zmianami ilości poli-ADP-rybozy i ekspresją Ki-67. Wnioski: Uzyskane przez autorów wyniki wskazują, że oprócz zmian ekspresji białka p53 jego potranslacyjna fosforylacja uczestniczy w regulacji proliferacji komórek nowotworowych pod wpływem leków.Introduction: p53 protein is a critical regulator of cell cycle and apoptosis. Many stimuli change its expression and modify its functions. The aim of our work was to determine stability and chosen posttranslational modification of p53 protein during the treatment of lung cancer. Material and methods: We investigated levels of poly-ADP-ribose- a marker of cellular DNA damage, DNA ploidy, Ki-67 expression, wild type and mutated p53 protein expression and intensity of phosphorylation of chosen p53 serine sites: C-terminal Ser392, and N-terminal Ser15, and Ser20 in fiberoptic bronchoscopy biopsy samples taken from patients suffering from recurrent squamous cell lung cancer before and after radio/chemotherapy. Analysis was based on results obtained from 23 patients after surgery in I-IIIA clinical stage of the disease. Results: Therapy lowered the number of G2/M cells, but increased S fraction cell population in about 50%. Therapy increased p53 expression and p53 phosphorylation at Ser392 and Ser20, and these changes correlated with poly-ADP-ribose levels and Ki-67 expression. Conclusions: Our results indicate that apart from changes in p53 quantity, p53 posttranslational phosphorylation play a role in regulation of neoplastic cells proliferation in response to drugs

Lymphatic vessel invasion detected by the endothelial lymphatic marker D2-40 (podoplanin) is predictive of regional lymph node status and an independent prognostic factor in patients with resected esophageal cancer

The discovery of markers to lymphatic endothelial cells and the development of novel antibodies to these markers have brought increasing attention to the lymphatics and progress in the understanding of lymphangiogenesis and cancer metastasis. In this study, we investigate the presence of lymphatic vessel invasion (LVI) detected by D2-40 immunohistochemical staining in resected esophageal cancer and correlated with clinicopathologic data and patient survival. Sixty nine patients, who had a primary resection of esophageal cancer, were analyzed by univariate and multivariate logistic regression, and univariate and multivariate survival analysis. The total rate of LVI was 72% (50/69). Positive LVI was significantly correlated with lymph node metastasis (p < 0.001), tumor size (p < 0.001), histological grading (p = 0.017), tumor depth (p = 0.001), and stage (p < 0.001). Multivariate logistic analysis identified LVI (p = 0.036) as a predictor of regional lymph node metastasis. On univariate survival analysis, patients with LVI had a significantly shorter disease-free survival, cancer-specific survival and overall survival. Multivariate analysis proved that LVI diagnosed by D2-40 is an independent prognostic factor of both disease-free survival (p = 0.04) and overall survival (p = 0.032) in resected esophageal cancer. These results show that LVI assessment identifies patients at high risk for regional lymph node metastasis and that LVI is an independent prognostic factor in patients with esophageal cancer. <i>(Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 1, pp. 90–97

Expression of matrix metalloproteinase-9 in the neoplastic and interstitial inflammatory infiltrate cells in the different histopathological types of esophageal cancer.

Metalloproteinase-9 (MMP-9) is the proteolytic enzyme degrading type IV collagen, and plays important role in the invasiveness and metastatic potential of tumor cells. The aim of the current study was to compare the association between the intensity of MMP-9 expression in neoplastic cells and in the interstitial inflammatory infiltrate cells in esophageal cancer with clinicopathological features of esophageal cancer (EC) and in different histopatological types of EC, e.g. adenocarcinoma and esophageal squamous cell carcinoma. The study included 32 EC patients, 17 cases of squamous cell carcinoma and 15 cases of adenocarcinoma, verified histopatologically. The presence of MMP-9 in cancer tissue was investigated by immunohistochemistry on formalin-fixed, wax-embedded sections of esophageal cancers. The light microscopy was used to evaluate the expression of metalloproteinase-9 in cancer cells and in inflammatory infiltrate in the neoplastic interstitium in semi-quantitative scale. The expression of MMP-9 in cancer cells was positive in 81% of cases whereas in inflammatory cells - in 75% and increased with tumor stage, depth of tumor invasion (T factor) and lymph node metastases (N factor). In squamous cell cancer the MMP-9 expression in cancer cells and in inflammatory infiltrate was higher than those in adenocarcinoma. Mean value of MMP-9 expression in inflammatory cells was higher in early stages of EC, whereas mean expression of this enzyme in cancer cells increased with tumor stage. In conclusion, this is the first study comparing the expression of metalloproteinase-9 in cancer and inflamatory infiltrate cells in different histopatological types of esophageal cancer. We proved the synthesis of MMP-9 by cancer cells as well as by inflammatory cells and its correlation with tumor stage, tumor size, depth of tumor invasion and lymph node metastases. The results suggest the role of MMP-9 in esophageal tumorigenesis, although this issue requires further investigations