Ekspresija i obrada somatostatina u gušterači u razvoju i u duktalnom adenokarcinomu gušterače

Somatostatin is a gastrointestinal peptide hormone that inhibits growth of pancreatic cancer as reported by an increasing body of evidence. Yet this is not always the case. To clarify the controversy we aimed to identify the expression of somatostatin in developing human embryonic pancreatic tissue and pancreatic adenocarcinoma given that somatostatin positive cells were shown either into primitive pancreatic ductal epithelium or into pancreatic carcinoma. Tissue sections representing pancreatic fetal specimens (n=15) and ductal pancreatic adenocarcinoma specimens (n=15) were assessed using immunohistochemical methods for somatostatin expression. Normal primitive exocrine ductal epithelium and endocrine epithelium showed a definite, statistically significant, higher expression of somatostatin over neoplastic pancreatic tissue of mixed (ductal-endocrine) and pure ductal type (p1=0.021, p2=0.001, p3<0.0001and p4=0.003 respectively) during the 8th to the 10th week. No statistically significantly different expression of somatostatin in the mantle zone of the islets over neoplastic tissue of mixed (p5=0.16) and pureductal type (p6=0.65), from the 13th to the 24th week was demonstrated. Pancreatic cancer cells can express somatostatin in a model that reproduces the normal expression of the peptide by d-cells during embryonal organogenesis. Therapy aimed at pancreatic cancer must be targeted to somatostatin and analogues as a potential adjuvant novel option.Somatostatin je probavni peptidni hormon koji suzbija rast raka gušterače, za što postoji sve više dokaza. No to se ne događa uvijek. Cilj studije bio je utvrditi ekspresiju somatostatina u ljudskom embrijskom tkivu gušterače u razvoju i u adenokarcinomu gušterače, s tim da su na somatostatin pozitivne stanice dokazane ili u primitivnom duktalnom epitelu gušterače ili u karcinomu gušterače. Tkivni isječci koji su predstavljali uzorke fetalne gušterače (n=15) i uzorke adenokarcinoma gušterače (n=15) ispitani su pomoću imunohistokemijskih metoda za ekspresiju somatostatina. Normalan primitivni egzokrini duktalni epitel i endokrini epitel pokazao je konačnu, statistički značajno višu ekspresiju somatostatina iznad neoplastičnog tkiva gušterače miješanog (duktalno-endokrinog) i čistog duktalnog tipa (p1=0,021, P2=0,001, p3<0,0001 odnosno p4=0,003) tijekom 8. do 10. tjedna. Nije dokazana statistički značajno različita ekspresija somatostatina u ovojnom sloju (mantle zone, mantle layer) otočića iznadneoplastičnog tkiva miješanog (p5=0,16) i čistog duktalnog tipa (p6=0,65) od 13. do 24. tjedna. Dakle, stanice raka gušterače mogu izražavati somatostatin na naein koji ponavlja normalnu d-staničnu ekspresiju peptida za vrijeme embrijske organogeneze. Liječenje zbog raka gušterače usmjereno na somatostatin i njegove analoge moglo bi predstavljati novu mogućnosti adjuvantne terapije

Local immune response in serous papillary carcinoma of the endometrium

Objective: Serous papillary carcinomas of the endometrium are aggressive tumors that tend to permeate, in a very extensive fashion, to uterine and adnexal lymphatic and vascular channels at an early stage in their evolution, and are associated with a particularly gloomy prognosis. It is generally thought that even tumors apparently limited to the endometrium or confined to an endometrial polyp have a poor outcome. Our study points towards the value of HLADR antigen in the outcome of serous papillary endometrial cancer. Our aim was to assess the HLA-DR expression in inactive, endometrial intraepithelial carcinoma (EIC), and invasive serous carcinoma curretage specimens from the endometrial cavity, suggesting a role inimmune response to keep tumor proliferation in check. Study design: Thirty-one cases of inactive endometrium, twelve cases of EIC, and thirtynine cases of serous papillary invasive carcinoma curettings were evaluated for the detection of HLA-DR monoclonal antigen. T helper (TH) marker (CD4) in the tumor stroma of the relevant cases was also studied, given that it is now known that the dependence of immune responsiveness on the class II antigens reflects the central role of these molecules in presenting antigen to TH cells. Results: HLA-DR was expressed in 20 of 31 inactive endometrium (64.5%), 4 of 12 in EIC (33.3%), and in 10 of 39 serous papillary invasive carcinomas (25.6%). CD4 was expressed in 9 of 31 inactive endometrium (29%), 5 of 12 in EIC (42%), and in 26 of 39 serous papillary invasive carcinomas (67%). Conclusions: The results showed decreased expression of HLA-DR and increased expression of CD4 as the lesion progressed to malignancy. The aberrant expression of HLA-DR by epithelial cells of inactive endometrium, of EIC and of serous papillary invasive carcinomas agrees with the hypothesis of the inactive endometrium - carcinoma in situ sequence as the usual route for the development of serous papillary invasive carcinoma. The immune attract mechanism by low HLA-DR signaling seems to be of minor importance in the malignant and metastatic potential of the serous papillary endometrial tumours

UNREMITTING EARLY STAGE HODGKIN’S DISEASE: REPORT OF 7 CASES AND BONE MARROW TISSUE IMMUNOHISTOCHEMICAL MARKER STUDY

Bone marrow is infrequently implicated in early stages of Hodgkin’s disease. We studied the immunohistochemical bone marrow tissue of 7 out of 20 cases with early stage Hodgkin’s disease of the mixed cellularity variant, diagnosed by lymph node biopsy at initial presentation, not responding to radiotherapy alone, in order to examine possible marrow attack. A statistically significant prevalence of CD45, CD45RO, and CD4 positive infiltrates, to the advantage of unremitting hosts, was found. The predominance of CD4-positive cells in the bone marrow space might be suggestive of involvement in the process and could explain the abnormal cytokine production leading to reduced T-cell immunity and inefficient antitumor response despite the existence of a vast majority of reactive infiltrating immune cells