Opere edilen erişkin gliom olgularında P53 ve Kİ-67 değerleri ve prognoz üzerine etkileri
Küçük Resim Yok
Tarih
1998
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
51 Glial tümörler günümüzde halen çok farklı biyolojik davranışları ile klinisyenleri tedavi ve takibinde zor duruma düşüren en önemli santral sinir sistemi tümörleridir Aynı histolojik bulguları verse de total rezeksiyonda dahi çok kısa survey verdikleri halde parsiyel eksize edildikleri bazı durumlarda da uzun bir survey verebilmektedirler. Bu durumda tümör biyolojisini ve prognozunu daha belirgin şekilde ortaya koymak için pek çok çalışma yapılmıştır. Bu çalışmaların genetik alanda yoğunlaşması sonucunda tümör genetiği ortaya çıkmış ve "yüzyılın geni"olarak ifade edilen p53 geni bulunmuştur. Bu durumda özellikle glial tümörler üzerinde yapılan araştırmalarda mutasyonu sonucu tümör formasyonu oluşmasını baskılayan fonksiyonunun kaybı ile bu tümörlerin oluşumu arasında belirgin korelasyon bulunmuştur. Bu korelasyon her zaman bulunamamasına rağmen iyi diferansiye glial tümörlerden kötü diferansiye olanlara doğru p53 gen mutasyonunun ve mutant proteinin miktarının giderek arttığı yapılan pek çok laboratuvar ve klinik çalışmasında gösterilmiştir. Malign progresyon gösteren hücrelerin proliferasyon oranı benign lezyonlara göre oldukça fazladır. Bu yüzden kötü prognoz gösterirler. Bu proliferasyon miktarım ölçmek için yapılan çalışmalar sonucu Ki-67 nükleer antijeni bulunmuştur. Özellikle hücre siklusunun Gı,S,G2 ve M fazlarında saptandığı halde dinlenme fazında (G0)saptanamamıştır. Ki-67 antijeninin bir proliferasyon belirleyicisi olarak mitozdan daha objektif olduğu belirlenmiştir. Bu iki faktör birçok glial tümörün ve diğer natürlü tümörlerin prognostik çalışmasında birlikte ele alınmıştır. Olumlu sonuçlarla birlikte olumsuz sonuçlar da alınmıştır. Bu birbiriyle çelişen genel bilgiler ışığında bu çalışmada postoperatif dönemde alınan glial kökenli tümör materyallerinden immunohistokimyasal olarak boyanan p53 mutant proteini ve Ki-67 nükleer antijen oranlan tespit edilerek tümör histolojisi ve prognozu ile karşılaştırılmıştır. 59 glial tümör vakasında yapılan incelemeler sonucu histolojik olarak 35'inde GBM, 7'sinde anaplastik astrositom, 4'ünde oligodendrogliom, 4'ünde anaplastik oligodendrogliom, 3 'ünde oligoastrositom, 3 'ünde epandimom, 2' sinde derece II astrositom ve Tinde gemistositik astrositom tanıları elde edilmiştir. Olguların 35'i erkek, 25 'i kadındır. Preparat görüntülerinin nöropatoloji uzmanı tarafından değerlendirildikten sonra mikroskoptan visüel kamera aracılığı ile X40 büyütmede bilgisayara en yoğun boyalı 5 alan aktarılmıştır. Ekranda elde edilen görüntüden boyalı hücre nükleusları sayılarak işaretleme indeksleri belirlenmiştir. Ki-67 ve p53 için en yüksek işaretleme indeks değerleri sekonder52 GBM ve anaplastik oligodendrogliomlarda bulunmuştur. Sekonder GBM de Kİ-67 ortalama 30,80 (±17,44) ve p53 ortalama 45,56 (±2,23), anaplastik oligodendrogliomda ise Ki-67 ortalama 17,58 (±9,21) ve p53 ortalama 27,37 (±26,02) değerleri elde edilmiştir. Astro sitomlarda iyiden kötü diferansiye forma doğru iki parametrede de artış görülmüştür. Tümörler 4 grupta incelenerek korelasyonlar belirlenmiştir. Ki-67 ve p53 ile cinsiyet, yaş, tümör lokalizasyonu arasında istatistiksel korelasyon bulunmamıştır. Nüks sayısı ile orantılı ortalama değerler olmasına karşın istatistiksel anlam bulunamamıştır. Tümör derecesi ile anlamlı istatistiksel ilişki gözlenmiştir. Sağkalım analizlerinde p53 için %20 ve üzerindeki ve Ki-67 için %15 ve üzerindeki değerler kötü prognoz açısından olumlu bulunmuştur. Sonuç olarak, glial tümörlerde prognoz belirlenmesinde p53 ve Ki-67 işaretleme indeks değerlerinin önemi küçümsenemez. Özellikle gliomlu hastalarda malign transformasyona gidecek olan ve histolojik açıdan daha benign karakter çizen tümörlerin önceden belirlenmesinde ve postoperatif uygulanacak tedavi protokolünü belirlemede oldukça faydalı sonuçlar verecek parametrelerdir
Nowadays, gliomas that clinicians raise difficulties to treatment and follow them with their different biologic behaviors are the most important tumours of the central nervous system. Glial tumours may give long life-time for patients in some situatinons of partial surgical resection of them despite they may give short life-time for patients in total resections of them at the same histologic groups. Thus, a lot of studies have done for clearly bring to light of biologic behavior and prognosis of gliomas. From results of these studies which genetics of tumour have been arised and p53 gene thus "the gene of this century" was discovered by these authors. In this stiuation, especially, it has been found manifest correlation between lose of depression of tumour formation of p53 functions and growth of glial tumours from result of p53's mutation. It has been observed that progressive increase level of mutations of p53 gene and mutant p53 protein from benign glial tumours to malign forms in a lot of laboratorial and clinical studies despite this correlation always has not been. The rate of proliferation of cells that show malignant progression has been increased than the benign lesions. For thus reason this cells show a bad prognosis. Ki-67 nuclear antigen was discovered from result of studies that has been done for the measurement of the proliferation rates.Ki-67 has been observed in Gı, S, G2 and M54 phases of the cell cycle despite it has not been observed in Go phase of the cell cycle. It has been determined as more objective parameter from mitosis in define proliferation. This two factors have been together taken for prognostic investigation of many glial and other tumours. Negative results have been recorded as well despite the positive results. Under the light of contradictory general informations,, the rates of mutant p53 protein and Ki-67 nuclear antigen that have been painted with immunohistochemical method from tumour materials of gliomas that have been obtained in postoperative period have been determined in this study. Later, this rates have been compared to histological features and prognosis of tumour. Investigations were obtained from the histological features of 59 patients: 35 were GBM, 7 were AA, 4 were oligodendroglioma, 4 were anaplastic oligo, 3 were oligoastrocytoma, 3 were ependimoma, 2 were grade II astrocytoma and 1 was gemistocytic astrocytoma. The patients included 35 males: and 25 females. Each slide was utilized by neuropathologist. Later, the different five areas of each slide which were appeared to have the highest density of labeled nuclei were selected and transformed from microscope to computer at magnification of x40 by visual camera. Labeled indices of cells have been determined with counting from obtained images in screen of computer. The highest amount of labeled nuclei for p53 and Ki-67 were obtained in GBM and oligodendrogliomas. Ki-67 mean labeling indices were 30.80% (±17.44) and p53 mean labeling indices were 45.56 % (±2.23) in secondary GBM. Same values for anaplastic oligodendrogliomas 17.58% (±9.21) and 27.37% (±26.02) respectivelly. Higher values were obtained in an incerasing form as progressing from benign to malign differantiations in astrocytomas. Correlations were determined between tumors that have been investigated in four groups. Statistical correlations were not found between these markers and sex, age, tumours of patients and sites of the tumours. Statistical significance was not found between the number of recurrence and with these markers, despite there was a proportional correlation between them. Significance statistical correlation was obtained between these markers (p53 and Ki- 67) and the grading p53 of tumours.55 Twenty percentage and above values for p53 and 15% and above values for Ki-67 were found a positive aspect of a prediction for a bad prognosis in survival analysis. As a consequence, importance of p53 and Ki-67 labeling indices, in together, should not taken into underestimation in definition of the prognosis of glial tumours. Especially, these parameters may give useful results to predict the glial tumour that will progress to malign transformation and show more benign character with histologic features. So, they may give useful results to determine a treatment protocol of postoperative duration for patients with this glial tumours.
Nowadays, gliomas that clinicians raise difficulties to treatment and follow them with their different biologic behaviors are the most important tumours of the central nervous system. Glial tumours may give long life-time for patients in some situatinons of partial surgical resection of them despite they may give short life-time for patients in total resections of them at the same histologic groups. Thus, a lot of studies have done for clearly bring to light of biologic behavior and prognosis of gliomas. From results of these studies which genetics of tumour have been arised and p53 gene thus "the gene of this century" was discovered by these authors. In this stiuation, especially, it has been found manifest correlation between lose of depression of tumour formation of p53 functions and growth of glial tumours from result of p53's mutation. It has been observed that progressive increase level of mutations of p53 gene and mutant p53 protein from benign glial tumours to malign forms in a lot of laboratorial and clinical studies despite this correlation always has not been. The rate of proliferation of cells that show malignant progression has been increased than the benign lesions. For thus reason this cells show a bad prognosis. Ki-67 nuclear antigen was discovered from result of studies that has been done for the measurement of the proliferation rates.Ki-67 has been observed in Gı, S, G2 and M54 phases of the cell cycle despite it has not been observed in Go phase of the cell cycle. It has been determined as more objective parameter from mitosis in define proliferation. This two factors have been together taken for prognostic investigation of many glial and other tumours. Negative results have been recorded as well despite the positive results. Under the light of contradictory general informations,, the rates of mutant p53 protein and Ki-67 nuclear antigen that have been painted with immunohistochemical method from tumour materials of gliomas that have been obtained in postoperative period have been determined in this study. Later, this rates have been compared to histological features and prognosis of tumour. Investigations were obtained from the histological features of 59 patients: 35 were GBM, 7 were AA, 4 were oligodendroglioma, 4 were anaplastic oligo, 3 were oligoastrocytoma, 3 were ependimoma, 2 were grade II astrocytoma and 1 was gemistocytic astrocytoma. The patients included 35 males: and 25 females. Each slide was utilized by neuropathologist. Later, the different five areas of each slide which were appeared to have the highest density of labeled nuclei were selected and transformed from microscope to computer at magnification of x40 by visual camera. Labeled indices of cells have been determined with counting from obtained images in screen of computer. The highest amount of labeled nuclei for p53 and Ki-67 were obtained in GBM and oligodendrogliomas. Ki-67 mean labeling indices were 30.80% (±17.44) and p53 mean labeling indices were 45.56 % (±2.23) in secondary GBM. Same values for anaplastic oligodendrogliomas 17.58% (±9.21) and 27.37% (±26.02) respectivelly. Higher values were obtained in an incerasing form as progressing from benign to malign differantiations in astrocytomas. Correlations were determined between tumors that have been investigated in four groups. Statistical correlations were not found between these markers and sex, age, tumours of patients and sites of the tumours. Statistical significance was not found between the number of recurrence and with these markers, despite there was a proportional correlation between them. Significance statistical correlation was obtained between these markers (p53 and Ki- 67) and the grading p53 of tumours.55 Twenty percentage and above values for p53 and 15% and above values for Ki-67 were found a positive aspect of a prediction for a bad prognosis in survival analysis. As a consequence, importance of p53 and Ki-67 labeling indices, in together, should not taken into underestimation in definition of the prognosis of glial tumours. Especially, these parameters may give useful results to predict the glial tumour that will progress to malign transformation and show more benign character with histologic features. So, they may give useful results to determine a treatment protocol of postoperative duration for patients with this glial tumours.
Açıklama
Bu tezin, veri tabanı üzerinden yayınlanma izni bulunmamaktadır. Yayınlanma izni olmayan tezlerin basılı kopyalarına Üniversite kütüphaneniz aracılığıyla (TÜBESS üzerinden) erişebilirsiniz.
Anahtar Kelimeler
Nöroşirürji, Neurosurgery, Genler-P53, Genes-P53, Glioma, Glioma, Neoplazmlar, Neoplasms, Prognoz, Prognosis
