Gastrointestinal stromal tümörlerde histopatolojik, tanısal ve prognostik bulguların değerlendirilmesi
The evaluation of histopathological, diagnostic and prognostic features of gastrointestinal stromal tumors
Yazar: FİLİZ ÇEVLİK
Danışman: PROF. FİGEN DORAN
Çukurova Üniversitesi / Tıp Fakültesi / Patoloji Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2006
Konu: Patoloji = Pathology

Özet:
ÖZETGastrointesitinal Stromal Tümörlerde Histopatolojik, Tan sal ve PrognostikBulgular n De erlendirilmesiGastrointestinal stromal tümörler (G ST) gastrointestinal trakt n en s k görülenmezenkimal tümörleridir. G ST'ler benignden maligne kadar geni bir davran spektrumunasahiptir. Literatürde G ST'lerin kötü gidi ini tahmin etmede risk gradelemesinin tümörboyutu ve mitotik oran baz al narak yap lmas gerekti i önerilmi tir. Bu çal man n amactümör boyutu, mitotik oran gibi konvansiyonel fakörlere ek olarak klinikopatololojikparametreler, risk gradei ve c-kit, CD34, S100, SMA, desmin, Ki-67, p53, bcl-2, bax, cox-2,PDGFR 'n n prognostik de erini ara t rmakt r.Bu çal mada 1995-2006 y llar aras nda rezeke edilmi G ST'ler ve gastrointestinalsistemin di er mezenkimal tümörlerine (leiomiyom, leiomyosarkom vb.) immünhistokimyasalyöntemle c-kit, CD34, SMA, S100 ve desmin uygulanm t r. Bu olgulardan G ST tan salanlara prognostik de erlendirme amaçl ki-67, p53, bcl-2, bax, cox-2, PDGFRçal lm t r.Yirmiyedi olguda tümör ince barsakta, 20 olguda midede, 6 olguda omentumda, 4olguda kal n barsakta, 2 olguda özefagusta lokalizeydi. Makroskopik olarak tümör boyutu 20-250mm aras ndayd (ortalama: 104mm). C-kit pozitif 60 olgu ve c-kit negatif 1 olgu, 12 olgudü ük risk gradeli, 8 olgu orta risk gradeli, 35 olgu yüksek risk gradeli olmak üzere riskgruplar na klasifiye edildi. Çok dü ük risk grubuna giren olgu yoktu. 6 olgu tümör çap n nbilinmemesi nedeniyle gradelenemedi. Risk gradei metastaz/rekürrens varl yla istatistikselolarak anlaml bulunmad . Mikroskopik olarak tümör, i si hücrelerden (40 olgu), epiteloidhücrelerden (7 olgu) ve mikst hücrelerden (14 olgu) olu maktayd . Fokal hemoraji ve nekrozgörüldü. Altm bir G ST olgusundan, 43'ü (70,5%) CD34, 34'ü (55,7%) SMA, 40' (65,6%)S100, 9'u (14,8%) desmin, 44'ü (72,1%) ki67, 17'si (29,3%) p53, 48'i (%82,8) bcl-2, 19'u(32,8%) bax, 56's (96,6%) cox-2 ve 48'i (78%) PDGFR ile pozitifti.Ki-67 ekspresyonu risk gradei ve mitozla koraleydi. Tümör nekrozu da risk gradei ilekoraleydi. Bu çal ma G ST'lerin malign potansiyelinin ya , cinsiyet, tümör lokalizasyonu,büyüme paterni, ülserasyon, hücre tipi, nükleer atipi, sellülarite, kanama ve c-kit, CD34,SMA, S100, desmin, p53, bcl-2, bax, cox-2, PDGFR ekspresyonu ile ilgili olmad ngöstermi tir.Ki-67 labeling index ve tümör nekrozu malign potansiyeli tahmin etmede ve cerrahitedavi eklini belirleme, takip ve adjuvan terapi gereklili ine karar vermede yard mc olabilir.Anahtar sözcükler: Gastrointestinal Stromal Tümör, c-kit, CD34, S100, SMA,Desmin, Ki-67, P53, Bcl-2, Bax, COX-2, PDGFR.

Abstract:
ABSTRACTThe Evaluation of Histopathological, Diagnostic and Prognostic Features ofGastrointestinal Stromal TumorsGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumorsof the gastrointestinal tract. GISTs have a wide spectrum of biologic behavior ranging frombenign to malignant. Risk grading based on tumor size and mitotic counts has been proposedin an effort to predict the adverse outcome of GIST in the literature so far. The aim of thisstudy was to elucidate the prognostic values of clinicopathological parameters, risk grade andC-kit, CD34, S100, SMA, Desmin, Ki-67, P53, Bcl-2, Bax, COX-2, PDGFR , in addition tothe conventional factors including tumor size, mitotic counts.In this study diagnostic immunohistochemical staining with C-kit, CD34, SMA, S-100and desmin were performed in patients with previously diagnosed GIST and othermesenchymal tumors (leiomyoma, leiomyosarcoma etc.) of gastrointestinal tract whounderwent resection from 1995 to 2006. Ki-67, P53, Bcl-2, Bax, COX-2, PDGFR stainingwere performed on tumors rediagnosed as gastrointestinal stromal tumor for the prognosticevaluation.There were 27 tumors located in the small intestine, 20 in the stomach, 6 omentum, 4large intestine, 2 esophagus. Grossly, the tumor size was between 20 and 250mm (mean:104mm). 60 cases of c-kit positive and one c-kit negatif GISTs were classified into, 12 casesof low-risk grade, 8 cases of intermediate-risk grade, and 35 cases of high-risk grade. Therewas no case of very low-risk grade. Six cases were excluded from the histopathologicalgrading because of unknown tumor size. The risk grade was not significantly associated withthe presence of metastases and/or recurrence. Microscopically, the tumor was composed ofspindle cells (40 cases), epithelioid cells (7 cases) and mixed cells (14). Focal hemorrhage,necrosis could be seen. Among the 61 cases of GIST, 43 (70,5%) were positive for CD34, 34(55,7%) for SMA, 40 (65,6%) for S100, 9 (14,8%) for desmin, 44 (72,1%) for Ki67, 17(29,3%) for p53, 48 (%82,8) for bcl-2, 19 (32,8%) for bax, 56 (96,6%) for cox-2 and 48(78%) for PDGFR .Ki-67 expression was correlated with risk grade and mitosis. The tumor necrosis wasalso correlated with risk grade. The study also indicated that the malignant potential of GISTis not correlated with the age, sex, tumor location, growth pattern, ulceration, cell type,nuclear atypia, high cellularity, tumor hemorrhage , expression of c-kit, CD34, SMA, S100,desmin, p53, bcl-2, bax, cox-2, PDGFR .Ki-67 labeling index and tumor necrosis may be useful in predicting malignantpotential, and therefore help to determine the surgical treatment, follow-up manner, and thenecessity of adjuvant therapy.Key words: Gastrointestinal Stromal Tumor, c-kit, CD34, S100, SMA, Desmin, Ki-67, P53, Bcl-2, Bax, COX-2, PDGFR .