Publication: Endometrial karsinomlarda pten, beta-catenin, p53, cerb-b2, ki67 ve stk 15 immunhistokimyasal belirteçlerinin tümör tipini belirlemede yeri ve patolojik prognostik parametrelerle ilişkisi
Abstract
Amaç: Endometrial karsinom (EK) olgularında; PTEN, β-catenin, P53, cerb- B2, Kİ67 ve STK 15 immunhistokimyasal (İHK) belirteçlerini kullanarak; bu belirteçlerin histolojik tiplendirmede tanısal yararını saptamak ve tümör evresi, tümör derecesi, myometrial invazyon derinliği, lenfovasküler invazyon varlığı, gibi patolojik prognostik parametrelerle ilişkisini değerlendirmek. Materyal ve Metod: 2008-2015 yıllları arasında retrospektif olarak incelenen, EK tanılı histerektomi olgularından seçilen 98 tümör bloğuna; PTEN, β-catenin, P53, cerb-B2, Kİ67 ve 53 tümör bloğuna STK 15 İHK boyaları uygulandı. İHK sonuçları semikantitatif olarak değerlendirilerek istatistiksel analiz yapıldı. Bulgular: Histolojik tiplerle göre boyanma düzeyleri karşılaştırıldığında; PTEN kaybı ve β-catenin ekspresyon artışı endometrioid tipte belirginken, P53, cerb-B2, Kİ67 ve STK 15 ekspresyon artışlarının nonendometrioid (NE) tümörlerde belirgin oluşu anlamlı saptanmıştır. Ayrıca bu belirteçlerin kombine kullanımlarının (PTEN+ β-catenin; endometrioid tip ve P53+ cerb-B2+ Kİ67; NE tip) histolojik tiplendirmede anlamı istatistiksel olarak daha da belirgindir. Boyanma düzeylerinin evre ile ilişkinde ise; P53 ve STK 15 ekspresyon artışlarının ileri evrelerde (evre 3 ve 4) daha yüksek oluşu anlamlı bulunmuştur. Endometrioid tip tümörlerde grade ile boyanma düzeyleri karşılaştırıldığında; Kİ67 ve STK 15 ekspresyon artışları, yüksek grade olgularda belirgin olarak izlenmiştir. Myometrial invazyon derinliği ile boyanma düzeyleri ilişkisinde ise; belirteçlerin hiçbirinin istatistiksel olarak anlamlı ilişkisi gösterilemese de, invazyon III olmayan olgulara göre, >%50 invazyon izlenen olgularda cerb-B2 ve P53 ekspresyonlarının artmış olduğu tespit edilmiştir. Lenfovasküler invazyon ile boyanma düzeyleri karşılaştırıldığında; P53 ve STK 15 ekspresyonunun lenfovasküler invazyon olan olgularda artmış olarak izlenmesi anlamlı bulunmuştur. (p<0.01 ve p<0.05 ) Sonuç: PTEN nükleer ekspresyon kaybı ve β-catenin nükleer ekspresyon artışı tek tek ya da kombine olarak endometrioid tip karsinomları belirlemede tanısal olarak kullanılabilir. P53’ün kuvvetli diffüz ekspresyonu, Cerb-B2 membranöz ekspresyonu, Kİ67 proliferasyon indeksi artışı tek tek ya da kombine olarak ve STK 15 nükleer+sitoplazmik ekspresyon artışı NE karsinomlarla ilişkilidir ve tanıda kullanılabilir. Ayrıca p53, Kİ67 ve STK 15 belirteçleri tümör tanısı dışında; evre, grade ve lenfovasküler invazyon gibi prognostik parametrelerle de ilişkili olduğundan tümörün prognoz tahmininde de yarar sağlayabilir. Ancak prognoz konusunda kesin yorumlar yapabilmek için; tümör tipi, evre ve derece gibi parametrelerin homojen dağılımının olduğu geniş olgu serilerinde, survi analizleriyle birlikte daha fazla inceleme yapmak gerekmektedir.
ÖZET(ABSTRACT) Aim: Our aim is to evaluate the expression of PTEN, β-catenin, P53, cerb-B2, Kİ67 and STK 15 immunohistochemical markers in endometrial carcinoma in order to investigate their diagnostic advantage in histologic subtypes and to correlate each marker with prognostic factors like; tumor stage, tumor grade, depth of myometrial invasion and lymphovascular invasion. Material and Method: Ninety-eight histerectomy specimens diagnosed as endometrial carcinoma, between 2008-2015 were included in our study. Sections from selected tumor blocks were stained immunohistochemically using; PTEN, β- catenin, P53, cerb-B2, Kİ67 and STK 15 antibodies. Results obtained from semi quantitative analyses were evaluated statistically. Findings: When histologic types and expression levels were compared, PTEN loss and β- catenin overexpression were significant in endometriod carcinomas, while P53, cerb- B2, Kİ67 and STK 15 overexpressions were significant in nonendometrioid (NE) tumors. Also the combined use of these markers (PTEN+ β-catenin; endometrioid type and P53+cerb-B2+Kİ67; NE type) was even more significant, in the differentiation of histologic types. There was a significant correlation between p53 and STK 15 expression in advanced stages (stages 3 and 4). When we compared expression of markers in various grades of endometrioid type tumors; increase in Kİ67 and STK 15 expressions were prominent in high grade cases. Even though the correlation between the expression of markers and depth of myometrial invasion was not statistically significant with any of the markers, overexpression of cerb-B2 and p53 was detected in >%50 invasive cases, as opposed to noninvasive cases. By comparing the expression of markers and lymphovascular invasion, we detected a significant increase of p53 and STK 15 expression in cases with lymphovascular invasion. Conclusion: Loss of nuclear PTEN expression and β-catenin nuclear overexpression can be used as an individual or combined diagnostic marker in endometrioid type carcinoma. Strong and diffuse expression of p53, membranous expression of cerb-B2 and increase of ki67 proliferation index as an individual or combined marker, and STK 15 nuclear+cytoplasmic overexpression as an individual marker are correlated with NE carcinomas and can be used in their diagnosis. P53,Kİ67 and STK 15 expression levels, because of their correlation with prognostic parameters like stage, grade and lymphovascular invasion, can also be useful in estimating the prognosis. However, to make a better estimate of prognosis; more investigations and more analyses of series with homogenous distrubition of parameters like; tumor type, stage, grade and survey analyses are required.
ÖZET(ABSTRACT) Aim: Our aim is to evaluate the expression of PTEN, β-catenin, P53, cerb-B2, Kİ67 and STK 15 immunohistochemical markers in endometrial carcinoma in order to investigate their diagnostic advantage in histologic subtypes and to correlate each marker with prognostic factors like; tumor stage, tumor grade, depth of myometrial invasion and lymphovascular invasion. Material and Method: Ninety-eight histerectomy specimens diagnosed as endometrial carcinoma, between 2008-2015 were included in our study. Sections from selected tumor blocks were stained immunohistochemically using; PTEN, β- catenin, P53, cerb-B2, Kİ67 and STK 15 antibodies. Results obtained from semi quantitative analyses were evaluated statistically. Findings: When histologic types and expression levels were compared, PTEN loss and β- catenin overexpression were significant in endometriod carcinomas, while P53, cerb- B2, Kİ67 and STK 15 overexpressions were significant in nonendometrioid (NE) tumors. Also the combined use of these markers (PTEN+ β-catenin; endometrioid type and P53+cerb-B2+Kİ67; NE type) was even more significant, in the differentiation of histologic types. There was a significant correlation between p53 and STK 15 expression in advanced stages (stages 3 and 4). When we compared expression of markers in various grades of endometrioid type tumors; increase in Kİ67 and STK 15 expressions were prominent in high grade cases. Even though the correlation between the expression of markers and depth of myometrial invasion was not statistically significant with any of the markers, overexpression of cerb-B2 and p53 was detected in >%50 invasive cases, as opposed to noninvasive cases. By comparing the expression of markers and lymphovascular invasion, we detected a significant increase of p53 and STK 15 expression in cases with lymphovascular invasion. Conclusion: Loss of nuclear PTEN expression and β-catenin nuclear overexpression can be used as an individual or combined diagnostic marker in endometrioid type carcinoma. Strong and diffuse expression of p53, membranous expression of cerb-B2 and increase of ki67 proliferation index as an individual or combined marker, and STK 15 nuclear+cytoplasmic overexpression as an individual marker are correlated with NE carcinomas and can be used in their diagnosis. P53,Kİ67 and STK 15 expression levels, because of their correlation with prognostic parameters like stage, grade and lymphovascular invasion, can also be useful in estimating the prognosis. However, to make a better estimate of prognosis; more investigations and more analyses of series with homogenous distrubition of parameters like; tumor type, stage, grade and survey analyses are required.