Компаративна анализа имунохистохемијске експресије Stathminа1, Ecadherina, Ki67, p53 и bcl2 у интестиналном и дифузном карциному желуца

Abstract

Cilj rada je korelativna analiza imunohistohemijske ekspresije Stathmina 1, Ki67, Ecadherina, Bcl-2 i p53 u intestinalnom i difuznom karcinomu želuca sa klasičnim prognostičkim parametrima tumora. Korišćen je biopsijski operativni materijal Hirurške klinike KBC Zemun. Prvu ispitivanu grupu (n =45) su činile operativne biopsije sa intestinalnim adenokarcinomom želuca, a drugu (n =45) su činile operativne biopsije difuznog adenokarcinoma želuca. Kontrolnu grupu obje ispitivane grupe, predstavljaju operativne biopsije netumorskog tkiva želuca, iz okoline tumora. Nakon rutinske obrade tkiva i kalupljenja u parafin, na presjecima debljine 4μm su primjenjene klasična HE i imunohistohemijska ABC metoda sa anti – Stathmin 1, Ki67, E-cadherin, p53 i Bcl-2 antitijelima . U intestinalnom adenokarcinomu ni jedan od ispitivanih onkoproteina ne zavisi od pola i lokalizacije tumora. Stathmin 1 je u značajnoj vezi sa ekspresijom p53 i invazijom krvnih sudova. Ekspresija p53 je značajno povezana sa starosnom dobi i histološkim gradusom, a ekspresija Ki67 je u značajnoj vezi sa ekspresijom Bcl-2, histološkim gradusom, invazijom limfnih sudova, pT statusom, metastazama u limfnim čvorovima i stadijumom tumorske bolesti. E-cadherin je u značajnoj inverznoj korelaciji sa ekspresijom Bcl-2, invazijom limfnih i krvnih sudova, metastazama u limfnim čvorovima, udaljenim metastazama i stadijumom tumorske bolesti. Bcl-2 je značajno povezan sa makroskopskim tipom tumora, histološkim gradusom, invazijom limfnih i krvnih sudova, metastazama u limfnim čvorovima i stadijumom bolesti. U difuznom adenokarcinomu je Stathmin 1 povezan visokim koeficijentima korelacije sa ekspresijom Ki67, p53, E-cadherin, Bcl-2, histološkim gradusom, invazijom limfnih i krvnih sudova, metastazama u limfnim čvorovima, udaljenim metastazama, pT statusom i stadijumom bolesti. ROC analiza je pokazala da senzitivnost za Stathmin 1, za difuzni adenokarcinom iznosi 72.9%, a specifičnost 67.6%, dok je senzitivnost za Ki67 66.7%, a specifičnost 65.6%. U difuznom adenokarcinomu je porast indeksa ekspresije Stathmina 1 praćen povećanim proliferativnim indeksom, redukcijom ćelijske adhezije, redukcijom apoptoze i porastom metastatskog potencijala, zbog čega ovaj onkoprotein može biti atratkivna terapijska meta u ciljanoj terapiji ovog tipa karcinoma želuca.

Comparative analysis of immunohistochemical expression of Stathmin 1, Ki67, Ecadherin, p53 and Bcl2 in intestinal and diffuse gastric cancer. The aim of this study was to correlate the immunohistochemical expression of Stathmin 1, Ki67, E-cadherin, Bcl-2 and p53 in intestinal and diffuse gastric cancer with classical tumor prognostic parameters. Biopsy operative material from the Surgical Clinic of KBC Zemun was used. The first examined group (n = 45) consisted of operative biopsies with intestinal gastric adenocarcinoma, and the second (n = 45) consisted of operative biopsies of diffuse gastric adenocarcinoma. The control group of both the first (n = 45) and second (n = 45) examined groups are operative biopsies of adjacent non-tumor gastric tissue. After routine tissue processing and paraffin molding, classical HE and immunohistochemical ABC methods with anti - Stathmin 1, Ki67, Ecadherin, p53 and Bcl-2 antibodies were applied on 4μm thick sections. In intestinal adenocarcinoma, none of the examined oncoproteins depends on the sex and localization of the tumor. Stathmin 1 is significantly associated with p53 expression and vascular invasion. P53 expression is significantly associated with age and histological grade, and Ki67 expression is significantly associated with Bcl-2 expression, histological grade, lymph vessel invasion, pT status, lymph node metastases, and disease stage. E-cadherin is significantly inversely correlated with Bcl-2 expression, lymph and blood vessel invasion, lymph node metastases, distant metastases, and disease stage. Bcl-2 is significantly associated with macroscopic tumor type, histological grade, lymph and blood vessel invasion, lymph node metastases, and disease stage. In diffuse adenocarcinoma, Stathmin 1 is associated with high correlation coefficients with the expression of Ki67, p53, E-cadherin, Bcl-2, histological grade, lymph and blood vessel invasion, lymph node metastases, distant metastases, pT status and stage. ROC analysis showed that the sensitivity for Stathmin 1, for diffuse adenocarcinoma is 72.9% and the specificity is 67.6%, while the sensitivity for Ki67 is 66.7% and the specificity is 65.6%. In diffuse adenocarcinoma, the increase in Stathmin 1 expression index is accompanied by increased proliferative index, reduction of cell adhesion, reduction of apoptosis and increase of metastatic potential, due to which this oncoprotein can be an attractive therapeutic target in targeted therapy of this type of gastric cancer.