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Cytophotometric study of the expression of the tumoral marker Factor VIII and prognostic factors in gastrci adenocarcinoma

Mary Tossa Nakamura Osvaldo Malafaia Ronaldo Mafia Cuenca Nicolau Gregori Czeczko Regina Maria da Cunha Teresa Cristina Santos Cavalcanti Carmen Austrália Paredes Marcondes Ribas Alexandre Eduardo Augustin Czeczko About the authors

INTRODUCTION: Regarding gastric cancer, the incidence, diagnosis and therapeutic options showed improvement in the last decades, but prognosis remains gloomy, specially due the fact that most patients, already diagnosed present advanced tumors, metastatic and not liable to be surgically resected. Molecular biology is an area in science, which can give the answer to many questions and current scientific facts show that the this should be through detection of tumoral markers. The great advances in informatics refined cell image analysis by image cytophotometry makes it possible to study cell proliferation and angiogenesis in various tumor processes using immunohistochemistry and several markers. At present, studies are conducted to demonstrate the prognostic value of their expressions, however, in gastric adenocarcinoma the results have been divergent and studies are scarce. AIM: To identify and quantify the expression of cell proliferation markers using Ki-67 and of angiogenesis with Factor VIII in gastric adenocarcinoma using cytophotometry, and compare their expressions with factors such as Bormanns´ classification, tumor invasion depth, degree of differentiation, nodal involvement, histologic pattern and age. METHODS: Twenty-one patients with gastric adenocarcinoma identified between 1998 and 2006 were studied. Ki-67 and Factor VIII expressions were performed using immunohistochemistry with clone MIB-1 primary antibodies, monoclonal for Ki-67 and policlonal for Factor VIII. Cytophotometric analysis was performed using the SAMBA 4000 system. RESULTS: Of the 21 patients 61.90% were males and 38.10% females, with a median age of 65 years. In our study eight patients had no Ki-67 marking (61,90% marking) and only one had no Factor VIII marking (95,24% marking). Means of Ki-67 labelling index was 33,25% (standard deviation 20,08, varying from 5,43 to 75,10) and of Factor VIII, 61,14% (standard deviation 15,06, varying from 29,16 to 73.91). There was no correlation between the two markers regarding gender and age. When compared between the two markers, expression for angiogenesis was significantly greater than that for cell proliferation with a mean difference between labelling index of 20,89 (p<0,001) and 15,26 standard deviation. There was no correlation between Ki-67 labelling index with comparative factors. However, regarding Factor VIII, tumors classified as III or IV present a significantly greater labelling index than those with Bormann I or II, but there was no correlation with tumor invasion depth, differentiation degree, nodal involvement and histologic pattern. CONCLUSIONS: 61,90% of the samples were identified and marked by Ki-67 and 95,24% by Factor VIII. In the marked tumors the mean Ki-67 labelling index was 33,25% and that of the Factor VIII, 61,14%. In the comparative study between the two markers, angiogenesis expression was significantly greater than that of cell proliferation. Regarding prognostic factors there was no significant correlation, except for Factor VIII and Bormanns´ classification in which type III or IV was greater than type I or II.

Gastric adenocarcinoma; Ki-67; Factor VIII; Image cytophotometry; SAMBA

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