Expression of p16, p53, CD24, EpCAM and Calretinin in Serous Borderline Tumors of the Ovary

Abstract

ÖZAmaç: Over kanserinin yaygın olarak kabul gören patogenez modeline gore bir seröz borderline tümör invaziv olmadan önce, noninvaziv mikropapiller aşamaya geçer veya tipik bir seröz borderline tümör zemininde mikroinvazyon yaparak invaziv aşamaya geçer. Bu çalışmanın amacı seröz borderline tümörler ve over dışı lezyonlarının seröz over kanseri patogenezindeki rolünü immunohistokimyasal bir panelle incelemektir. Gereç ve Yöntem:Tipik, fokal mikropapiller, mikropapiller, mikroinvaziv, kistadenom ve düşük dereceli karsinom alanları içeren 46 olguluk seröz borderline tümör grubuna p16, p53, CD24, EpCAM ve kalretininden oluşan immünohistokimyasal bir panel uygulandı. Bu panelin degerlendirilmesi icin seröz borderline tümörler gibi kistik/ince duvarlı ve heterojen neoplazileri incelerken lineer bir kesite bakma imkanı vermesi nedeni ile daha avantajlı olan "cutting edge" matriks-benzeri doku arrayleri hazırlandı. Bulgular:Tümör supresör gen grubunda değerlendirilen iki işaretleyici ile diffüz, kuvvetli p53 ekspresyonu hiçbir olguda saptanmaz iken,olguların tümünde p16 ile kuvvetli, heterojen ekspresyon izlendi. Kalretinin ile mikropapiller tümörlerde fokal kuvvetli ekspresyon izlenirken, EpCAM ile aynı alanlarda ekspresyon kaybı saptandı. Hücre adezyon moleküllerinin ekspresyon lokalizasyonlarındaki değişikliklerin fenotipte değişme ve tümör progresyonu ile ilişkili olabileceğini destekler şekilde, peritoneal implantların saptandığı olgularda sitoplazmik ve kuvvetli CD24 ekspresyonu görüldü. Lenf nodu tutulumu ve mikroinvazyon alanlarında çembersel membranöz ve sitoplazmik CD24 ve EpCAM ekspresyonu görüldü.Sonuç: Bulgular, seröz over tümörü progresyonunun farklı aşamala-rına EpCAM, CD24, ve kalretinin immünohistokimyasal ekspresyon paternindeki değişikliklerin eşlik edebildiğini göstermektedir.Anahtar Sözcükler: Over tümörleri, p16 proteini, p53 antijeni, CD24 antijeni, EpCAM proteini, Calretinin ABSTRACTObjective: According to the widely accepted pathway, a serous borderline tumor becomes invasive either by progressing into a noninvasive micropapillary tumor or directly through microinvasion. Our objective was to investigate the role of serous borderline tumors and their accompanying extraovarian lesions in pathogenesis of serous ovarian cancer using immunohistochemistry as a tool. Material and Method:An immunohistochemical panel of p16, p53, CD24, EpCAM and calretinin was applied to cutting edge matrix assembly-like tissue arrays of 46 cases consisting of typical, focal micropapillary, micropapillary, microinvasive, cystadenoma, and low-grade carcinoma cases. These tissue arrays are better choices than conventional tissue arrays to examine thin walled and heterogenous neoplasia like serous borderline tumors as they facilitate the analysis with linear sections rather than a core.Results: For two tumor supressor gene markers; no diffuse and strong expression of p53, and strong and patchy/heterogenous expression of p16 were detected in all cases. Focal and strong calretinin expression was detected in micropapillary tu...

The immunohistochemical expression of CD24 and CD171 adhesion molecules in borderline ovarian tumors

“…In addition, high-grade carcinomas and carcinomas with metastases to the omentum had considerably higher CD24 scores, confirming the results of previous reports [10][11][12][13][14]. The polarized apical expression of CD24 was maintained in benign cystadenomas and most borderline tumors, while progression to carcinoma made prominent a non-polarized, cytoplasmic expression of CD24, an observation made by other authors as well [10][11][12][13]. This change of expression pattern may be due to overproduction, disturbance of protein distribution or degradation within the cell [11].…”

“…This change of expression pattern may be due to overproduction, disturbance of protein distribution or degradation within the cell [11]. Accumulative data from our results and those of the literature [10][11][12][13] support the view that cytoplasmic expression of CD24 in a borderline or a malignant ovarian tumor may suggest a more aggressive phenotype.…”

“…In general, malignant tumors, especially those of higher histological grade and those with metastatic disease, tend to present stronger immunoreaction, while CD24 expression has been associated with survival and prognosis. Previous studies in ovarian cancer cases have shown that overexpression of CD24 is an independent factor associated with tumor metastasis, and poor survival [10][11][12][13][14]. In this study the expression of CD24 was considerably higher in borderline tumors and ovarian carcinomas than normal ovaries and benign neoplasms.…”

“…It is also expressed by hematopoietic cells and a variety of tumor cell lines [2,9]. We undertook the task of investigating these molecules in ovarian neoplasms, focusing on the borderline tumor category, since literature concerning the expression of these molecules in ovarian cancer is still limited [10][11][12][13][14][15][16].…”

Ascitis as a unique microenvironment of tumors in ovarian cancer: interaction with prognosis and chemoresistance

“…Экзосомы могут нести информацию о канцерогенезе, риске прогрессирования и прогнозировании выживаемости. Показано, что более высокие уровни CD24 при РЯ указывают на худший прогноз и более низкую выживаемость [53]. Также есть данные о том, что уровни EpCAM и CD24, присутствующие в экзосомах, коррелируют с агрессивностью РЯ [54].…”