İnvaziv duktal karsinoma olgularında histopatolojik parametreler ve prognostik faktörler ile nükleer morfometrik parametlerin karşılaştırılması
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Date
2005
Authors
İnal, Gülşah
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Journal ISSN
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Publisher
Uludağ Üniversitesi
Abstract
AMAÇ: İnvaziv duktal karsinoma olgularında histopatolojik parametreler ve prognostik faktörler ile tanı koyma ve prognozun belirlenmesinde objektif ve tekrarlanabilir oldukları çeşitli çalışmalarda gösterilmiş olan nükleer morfometrik parametrelerin karşılaştırılmasıdır. GEREÇ VE YÖNTEM: 1997-2004 yılları arasında Uludağ Üniversitesi Tıp Fakültesi Meme Cerrahisi Bilim Dalı tarafından invaziv duktal karsinoma nedeniyle modifiye radikal mastektomi ve aksiller lenf nodu diseksiyonu uygulanmış 75 kadın hasta çalışma kapsamına alındı. Olgulara ait Hematoksilen-Eozin (H&E) boyalı preparatlar patolojik parametreler açısından ışık mikroskobu altında incelendi. Olgular histolojik grade’e, Modifiye Bloom-Richardson yönteminde kullanılan parametreler için aldıkları puanlara, tümör çapına, lenf nodu metastazı ve nekroz bulunup bulunmadığına göre gruplandırıldı. Morfometrik çalışmada Scion Image Yazılım programı kullanılarak her bir olgu için rastgele seçilmiş 50 hücre işaretlendi. Program tarafından otomatik olarak nükleer alan ve nükleer çevre değerleri belirlendikten sonra bu ölçüm değerlerinin kullanıldığı formüllere göre şekil faktörü ve nükleer yuvarlaklık ölçütleri hesaplandı. Değişkenlerin normal dağılım gösterip göstermediği Shapiro-Wilk Testi ile test edildi. Normal dağılım gösteren değişkenler için iki grup karşılaştırmasında t-testi, üç ve daha fazla grup karşılaştırmasında tek yönlü varyans analizi kullanıldı. Tek yönlü varyans analizinde farklılık olması durumunda gruplar arasındaki farklılık Bon-ferroni Çoklu Karşılaştırma Testi ile incelendi. Normal dağılım göstermeyen değişkenlerde iki grup karşılaştırması için Mann-Whitney U Testi, üç ve daha fazla grup karşılaştırması için Kruskall Wallis Testi kullanıldı. Kategorik değişkenlerin karşılaştırılmasında Pearson Ki-Kare Testi kullanıldı. BULGULAR: Olguların histolojik ve nükleer grade’leri ile bütün morfometrik parametreler arasında anlamlı bir ilişki tespit edildi. İkili karşılaştırmalarda ise grade-1 ve grade-2 ile grade-1 ve grade-3 olgular arasında, yine mitoz sayısına göre 1 ve 2 puan alan olgular ile 2 ve 3 puan alan olgular arasında bütün morfometrik parametreler açısından anlamlı farklılık saptandı. Histolojik ve nükleer grade’e göre grade-2 ve grade-3 olgular arasında ise sadece nükleer alan ve çevre açısından anlamlı farklılık olduğu tespit edildi. Histolojik grade, nükleer grade ve mitoz sayısı arttıkça nükleer alan ve çevre değerlerinde de artış olduğu dikkati çekti. Tübül formasyonuna göre 2 ve 3 puan alan olgular arasında sadece nükleer alan açısından anlamlı farklılık saptandı. Lenf nodu metastazı olmayan olgulara göre, metastaz olan olgularda nükleer alan ve çevre değerlerinde hafif artış saptanırken bu parametreler arasında istatistiksel açıdan anlamlı bir ilişki tespit edilmedi. SONUÇ: Çalışmadaki verilere göre istatistiksel açıdan en güçlü ve anlamlı ilişkinin nükleer morfometrik parametreler ile histolojik ve nükleer grade arasında olduğu tespit edilmiştir. Yine histolojik ve nükleer grade arttıkça nükleer alan ve çevre değerleri de belirgin olarak artmaktadır. Kaynaklardaki bilgiler ile paralel olan bu bulgulara dayanarak morfometrik görüntü analiz yönteminin, invaziv duktal karsinoma olguları için en önemli prognostik faktörlerden biri olan grade’in belirlenmesinde objektif ve tekrarlanabilir bir yöntem olarak kullanılabileceği düşünülmüştür.
OBJECTIVE: To compare the nuclear morphometric parameters which are proved to be objective and reproducible in diagnosis and predicting prognosis by many studies with histopathologic parameters and prognostic factors in invasive ductal carcinoma. MATERIALS AND METHODS: Seventy–five women with invasive ductal carcinoma who had undergone modified radical mastectomy and axillary lymph node dissection at Uludag University Medical School Department of Breast Surgery were included in the study. Haematoxylin-Eosin (H&E) stained slides were reevaluated for the pathological parameters under the light microscope. Cases were grouped according to histological grade, number of points they got from the Modified Bloom-Richardson parameters, tumor dimension, lymph node metastasis, and presence of necrosis. In this morphometric study, randomly selected 50 cells from each case were labeled using Scion Image Analysis software programme. Nuclear area and nuclear perimeter were calculated automatically by the programme, and shape factor and nuclear rounding measures were calculated with formulas using these measured values. Whether the variables showed a normal range or not was tested with Shapiro-wilk test. For variables with a normal distribution rank, t test was used for comparing two groups and one-way variance analysis for comparing three or more groups. If there was difference in one-way variance analysis, difference between the groups were examined by Bon-ferroni multiple comparison test. For variables which did not show a normal distribution, comparison of two groups was done by Mann Whitney U test and Kruskall Wallis was used for three or more groups. Pearson chi-square test was used for categorical variables. FINDINGS: A meaningful relationship was found between the histological and nuclear grades and all morphometric parameteres. When comparing two variables there was a meaningful difference between cases which got 1 or 2 points and cases which got 2 or 3 points from mitosis; between grade-1 and 2 cases, and grade-1 and 3 cases. There was a meaningful difference, only with respect of nuclear area and perimeter, between histological and nuclear grade-2 and 3 cases. It was noted that nuclear area and perimeter values increased as histological grade, nuclear grade and the number of mitosis increased. Between the cases with 2 points and 3 points from tubuli formation, there was a meaningful relationship only in respect of nuclear area. Although there was a slight increase in nuclear area and perimeter values with metastatic cases compared with nonmetastatic ones, there was no statistically significant relationship between these parameters. RESULT: According to the data in this study the most statistically powerful and meaningful relationship was found between nuclear morphometric parameters and histological and nuclear grade. Again as the histological and nuclear grade increased, nuclear area and perimeter values also increased prominently. These findings are consistent with the knowledge we got from the literature, it is thought that morphometric image analysis technique can be used in invasive carcinoma of breast for predicting grade which is one of the most important prognostic factors.
OBJECTIVE: To compare the nuclear morphometric parameters which are proved to be objective and reproducible in diagnosis and predicting prognosis by many studies with histopathologic parameters and prognostic factors in invasive ductal carcinoma. MATERIALS AND METHODS: Seventy–five women with invasive ductal carcinoma who had undergone modified radical mastectomy and axillary lymph node dissection at Uludag University Medical School Department of Breast Surgery were included in the study. Haematoxylin-Eosin (H&E) stained slides were reevaluated for the pathological parameters under the light microscope. Cases were grouped according to histological grade, number of points they got from the Modified Bloom-Richardson parameters, tumor dimension, lymph node metastasis, and presence of necrosis. In this morphometric study, randomly selected 50 cells from each case were labeled using Scion Image Analysis software programme. Nuclear area and nuclear perimeter were calculated automatically by the programme, and shape factor and nuclear rounding measures were calculated with formulas using these measured values. Whether the variables showed a normal range or not was tested with Shapiro-wilk test. For variables with a normal distribution rank, t test was used for comparing two groups and one-way variance analysis for comparing three or more groups. If there was difference in one-way variance analysis, difference between the groups were examined by Bon-ferroni multiple comparison test. For variables which did not show a normal distribution, comparison of two groups was done by Mann Whitney U test and Kruskall Wallis was used for three or more groups. Pearson chi-square test was used for categorical variables. FINDINGS: A meaningful relationship was found between the histological and nuclear grades and all morphometric parameteres. When comparing two variables there was a meaningful difference between cases which got 1 or 2 points and cases which got 2 or 3 points from mitosis; between grade-1 and 2 cases, and grade-1 and 3 cases. There was a meaningful difference, only with respect of nuclear area and perimeter, between histological and nuclear grade-2 and 3 cases. It was noted that nuclear area and perimeter values increased as histological grade, nuclear grade and the number of mitosis increased. Between the cases with 2 points and 3 points from tubuli formation, there was a meaningful relationship only in respect of nuclear area. Although there was a slight increase in nuclear area and perimeter values with metastatic cases compared with nonmetastatic ones, there was no statistically significant relationship between these parameters. RESULT: According to the data in this study the most statistically powerful and meaningful relationship was found between nuclear morphometric parameters and histological and nuclear grade. Again as the histological and nuclear grade increased, nuclear area and perimeter values also increased prominently. These findings are consistent with the knowledge we got from the literature, it is thought that morphometric image analysis technique can be used in invasive carcinoma of breast for predicting grade which is one of the most important prognostic factors.
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Keywords
Meme kanseri, Morfometri, Görüntü analizi, Breast cancer, Morphometry, Image analysis
Citation
İnal, G. (2005). İnvaziv duktal karsinoma olgularında histopatolojik parametreler ve prognostik faktörler ile nükleer morfometrik parametlerin karşılaştırılması. Yayınlanmamış tıpta uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.