Radyoterapi uygulanan invazif mesane kanserli olgularda HER-2/neu protein overekspresyonunun prognoz ve sağkalıma etkisinin değerlendirilmesi
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Date
2009
Authors
Yılmaz, Eda Bengi
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Bu çalışmanın amacı invazif mesane kanseri tanısıyla küratif radyoterapi uygulanan olgularda HER-2/neu protein aşırı ekspresyonunun prognostik önemini ve sağkalıma etkisini değerlendirmekti.Çalışmaya 1996-2003 yılları arasında Uludağ Üniversitesi Tıp Fakültesi (UÜTF) Muammer Ağım (MA) Radyoterapi merkezinde invazif mesane kanseri tanısıyla mesane komplet transüretral rezeksiyonu (TUR-M) sonrası küratif radyoterapi uygulanan 51 olgu dahil edildi.Olguların patoloji spesmenleri HER-2/neu protein ekspresyonunu değerlendirmek üzere immunohistokimyasal olarak boyandı. Food and Drug Administration (FDA) onaylı DAKO kit kriterlerine göre membran boyanma yoğunluğu ve şiddeti skorlandı. Olguların incelenmesinde, beşinin negatif, 24'ünün (%47) (+), 20'sinin (%39) (++), ikisinin (%4) (+++) boyandığı saptandı. (++) ve (+++) olarak skorlananlar pozitif olarak gruplandırıldı.İstatistiksel analizlerde genel sağkalım (GSK) ve hastalığa özgü sağkalım için (HÖSK) Kaplan-Meier eğrileri, gruplar arası farklılıklar için log rank testi, çok değişkenli analizde Cox-regresyon testi kullanıldı. Prognostik faktörlerin incelenmesi Spearman korelasyon testi ile yapıldı. p değerinin ?0.05 olması istatistiksel olarak anlamlı kabul edildi.Ortanca 22 aylık (1-124) izlem süresi içerisinde lokal ve uzak yineleme sırasıyla yedi (%14) ve dokuz olguda (%18) görüldü. Olgular iki ve beş yıllık HÖSK ve GSK açısından incelendiğinde, HER-2/neu pozitif ve negatif grup arasında anlamlı farklılık görülmedi.Tek değişkenli analizde HER-2/neu pozitifliği ile T evresi (p=0.053), perinöral invazyon varlığı (p=0.052), metastaz gelişimi (p=0.051) ve GSK (p=0.058) arasında istatistiksel anlamlılığa yakın ilişki görülürken, tedaviye yanıt ile anlamlı ilişki saptandı (p=0.018).Sonuç olarak, HER-2/neu aşırı ekspresyonu invazif mesane kanserinde küratif kemoradyoterapiye yanıtı öngörmede bir faktör olabilir. Ancak çalışmamızda sağkalım üzerine bağımsız prognostik faktör olarak etkisi gösterilememiştir.
The aim of the study was to evaluate the effect of Her-2/neu overexpression on prognosis and survival in cases with invasive bladder cancer, who had undergone curative radiotherapy.Fifty one cases with invasive bladder cancer, who had been treated with curative radiotherapy after complete transurethral resection of bladder (TURB) at the Uludag University Faculty of Medicine (Muammer Agim Radiotherapy Center), between 1996-2003, were enrolled in the study.The pathological specimens were stained immunohistochemically to evaluate Her-2/neu expression. The membrane staining pattern and intensity was scored according to the Food and Drug Administration (FDA) approved DAKO criteria. Of all cases five were stained negative, 24 (47%) were stained (+), 20 were stained (39%) (++) and two (4%) were stained (+++). Tumors with scores of (++) and (+++) were considered as positive.In statistical analyses, overall survival (OS) and disease-specific survival (DSS) were evaluated by Kaplan-Meier curves, in univariate analysis log-rank test and in multivariate analysis Cox's regression model were used. Prognostic factors were analyzed with Spearman's Correlation test. A p value of ≤0.05 was considered as statistically significant.After a median follow-up time of 22 months (range: 1-124 months), local recurrence and distant metastasis were seen in seven (%14) and nine cases (%18), respectively. When the cases were analyzed with regard to two and five years DSS and OS, there were no significant differences between Her-2/Neu positive and negative groups.While the positivity of Her-2/neu was found to be borderline significance with T stage (p=0.053), presence of perineural invasion (p=0.052), metastasis (p=0.051), and OS (p=0.058), there was a significant association with treatment response (p=0.018).As conclusion, Her-2/neu overexpression might be a factor predicting response to curative chemoradiotherapy in invasive bladder cancer. However, its effect on survival as an independent prognostic factor could not be demonstrated in our study.
The aim of the study was to evaluate the effect of Her-2/neu overexpression on prognosis and survival in cases with invasive bladder cancer, who had undergone curative radiotherapy.Fifty one cases with invasive bladder cancer, who had been treated with curative radiotherapy after complete transurethral resection of bladder (TURB) at the Uludag University Faculty of Medicine (Muammer Agim Radiotherapy Center), between 1996-2003, were enrolled in the study.The pathological specimens were stained immunohistochemically to evaluate Her-2/neu expression. The membrane staining pattern and intensity was scored according to the Food and Drug Administration (FDA) approved DAKO criteria. Of all cases five were stained negative, 24 (47%) were stained (+), 20 were stained (39%) (++) and two (4%) were stained (+++). Tumors with scores of (++) and (+++) were considered as positive.In statistical analyses, overall survival (OS) and disease-specific survival (DSS) were evaluated by Kaplan-Meier curves, in univariate analysis log-rank test and in multivariate analysis Cox's regression model were used. Prognostic factors were analyzed with Spearman's Correlation test. A p value of ≤0.05 was considered as statistically significant.After a median follow-up time of 22 months (range: 1-124 months), local recurrence and distant metastasis were seen in seven (%14) and nine cases (%18), respectively. When the cases were analyzed with regard to two and five years DSS and OS, there were no significant differences between Her-2/Neu positive and negative groups.While the positivity of Her-2/neu was found to be borderline significance with T stage (p=0.053), presence of perineural invasion (p=0.052), metastasis (p=0.051), and OS (p=0.058), there was a significant association with treatment response (p=0.018).As conclusion, Her-2/neu overexpression might be a factor predicting response to curative chemoradiotherapy in invasive bladder cancer. However, its effect on survival as an independent prognostic factor could not be demonstrated in our study.
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Keywords
Mesane karsinomu, HER-2/neu, Kemoradyoterapi, Bladder cancer, Chemoradiotherapy
Citation
Yılmaz, E. B. (2009). Radyoterapi uygulanan invazif mesane kanserli olgularda HER-2/neu protein overekspresyonunun prognoz ve sağkalıma etkisinin değerlendirilmesi. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.