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P53, HER2/neu, Bcl-2 and PCNA overexpression in ductal carcinoma in situ lesions of the breast and their role in progression to invasive carcinoma

Yıl 2019, Cilt: 11 Sayı: 4, 490 - 496, 01.12.2019
https://doi.org/10.21601/ortadogutipdergisi.536772

Öz

Objective: Understanding proliferative activity and the changes in oncogenes and tumour supressor genes may be important to predict the ductal carsinoma in situ cases that have high probability of progression to invasive breast carcinoma. In this study the correlation between p53, HER2/neu, bcl-2 and PCNA overexpression and progression of ductal carsinoma in situ were evaluated.
Methods: We evaluated 20 ductal carsinoma in situ (group 1) and 20 ductal carsinoma in situ associated with invasive ductal carcinoma cases (group 2). We studied p53, HER2/neu, bcl-2 ve PCNA to cases immunohistochemically.
Results: P53, HER2/neu and PCNA overexpression were higher in group 2 cases. But differences were not significant statistically (p>0,05). Bcl-2 overexpression was seen 36.8% in group 1, 70% in group 2 cases. The difference between two groups was significant statistically (p<0,05). In our study, also one of the important finding was that p53, HER2/neu, bcl-2 and PCNA overexpression were revealed 3 cases in group 2 at the same time but was not seen in any of group 1 cases.
Conclusion: These findings showed that bcl-2 overexpression may be more important in progression of ductal carsinoma in situ to invasive ductal carcinoma, existing different pathways in development of invasive ductal carcinoma and revealing more than one of these changes in the same case may be more important in defining progression risk to invasive ductal carcinoma. These results contribute to define DCIS subtypes that have different biological behaviour.

Kaynakça

  • Mercier I, Gonzales DM, Quann K, ve ark. CAPER, a novel regulator of human breast cancer progression. Cell Cycle 2014 Apr 15; 13(8): 1256-1264.
  • Perez AA, Balabram D, Salles MA, Gobbi H. Ductal carcinoma in situ of the breast: correlation between histopathological features and age of the patients. Diagn Pathol. 2014; 9: 227-232.
  • Terry G, Ho L, Londesborough P, Duggan C, Hanby A, Cuzick J. The expression of FHIT, PCNA and EGFR in benign and malignant breast lesions. Br J Cancer 2007 Jan 15; 96(1): 110-117.
  • Tot T. DCIS, cytokeratins and the theory of the sick lobe. Virchows Arch 2005; 447: 1-8.
  • Gerber B, Müller H, Reimer T, Krause A, Friese K. Nutrition and lifestyle factors on the risk of developing breast cancer. Breast Cancer Res Treat 2003; 79(2): 265-276.
  • Gerber B, Mylonas I. Reduction of the risk of breast cancer. Zentralbl Gynecol 2003; 125(1): 6-16.
  • Pape-Zambito D, Jiang Z, Wu H, ve ark. Identifying a Highly-Aggressive DCIS Subgroups by Studying Intra-Individual DCIS Heterogeneity among Invasive Breast Cancer Patients. PLoS One. 2014; 9(6): e100488.
  • Shang M, Zhang X, Liu X, ve ark. P16 and P53 Play Distinct Poles in Different Subtypes of Breast Cancer. PLoS One. 2013; 8(10): e76408.
  • Menard S, Fortis S, Castiglioni F, Agresti R, Balsari A. HER-2 as a prognostic factor in breast cancer. Oncol 2001; 61: 67-72.
  • Barlett JMS, Nofech-Moses S, Rakovitch E. Ductal carcinoma in situ of the breast: can biomarkers improve current management. Clin Chem 2014; 60(1): 60-67.
  • Siziopikou KP, Khan S. Correlation of HER-2 gene amplification with expression of the apoptosis-suppressing genes bcl-2 and bcl-x-L in ductal carcinoma in situ of the breast. Appl Immunohistochem Mol Morphol 2005; 13: 14-18.
  • Keohavong P, Gao WM, Mady HH, Kanbour-Shakir A, Melhem MF. Analysis of p53 mutations in cells taken from paraffin-embedded tisue sections of ductal carcinoma in situ and atypical ductal hyperplasia of the breast. Cancer Lett 2004; 212(1): 121-130.
  • Mylonas I, Makovitzky J, Jeschke U, Briese V, Friese K, Gerber B. Expression of Her2/neu, Steroid Receptors (ER and PR), Ki-67, and p53 in Invasive Mammary Ductal Carcinoma Associated with Ductal Cacinoma In Situ (DCIS) Versus Invasive Breast Cancer Alone. Anticancer Res 2005; 25: 1719-1724.
  • Mommers ECM, Leonhart AM, Falix F, Michalides R, Meijer CJLM, Baak JP. Similarity in expression of cell cycle proteins between in situ and invasive ductal breast lesions of same differantiation grade. J Pathol 2001; 194: 327-333.
  • Mommers ECM, Van Diest PJ, Leonhart AM, Meijer CJLM, Baak JPA. Expression of proliferation and apoptosis-related proteins in usual ductal hyperplasia of the breast. Hum Pathol 1998; 29: 1539-1545.
  • Allred DC, Clark GM, Molina R, ve ark. Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol 1992; 23(9): 974-979.
  • Umekita Y, Takasaki T, Yoshida H. Expression of p53 protein in benign epithelial hyperplasia, atypical ductal hyperplasia, noninvasive and invasive mammary carcinoma. An immunohistochemical study. Virchows Arch 1994; 424(5): 491-494.
  • Hung MC, Lau YK. Basic science of HER-2/neu: a review. Semin Oncol 1999; 26: 51-59.
  • Roetger A, Merschjann A, Dittmar T, Jackisch C, Barnekow A, Brandt B. Selection of potentially metastatic subpopulations expressing c-erbB-2 from breast cancer tissue by use of an extravasation model. Am J Pathol 1998; 153: 1797-1806.
  • Hockenbery DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ. Bcl-2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci U S A 1991; 88: 6961-6965.
  • Stewart BW. Mechanisms of apoptosis: integration of genetic, biochemical, and cellular indicators. J Natl Cancer Inst 1994; 86(17): 1286-1296.
  • Siziopikou KP, Prioleau JE, Harris JR, Schnitt SJ. Bcl-2 expression in the spectrum of preinvasive breast lesions. Cancer 1996; 77: 499-506.
  • Sizopikou KP, Schnitt SJ. MIB-1 proliferation index in ductal carcinoma in situ of the breast: relationship to the expression of the apoptosis-regulating proteins bcl-2 and p53. Breast J 2000; 6(6): 400-406.
  • Niewiadomska H, Jeziorski A, Olborski B. The expression of the proliferating antigen Ki67, PCNA and products of gene p53 in primary invasive ductal breast carcinoma. J Exp Clin Cancer Res 1998; 17(4): 503-510.
  • Haerslev T, Jacobsen GK, Zedeler K. Correlation of growth fraction by Ki-67 and proliferating cell nuclear antigen (PCNA) immunohistochemistry with histopathological parameters and prognosis in primary breast carcinomas. Breast Cancer Res Treat 1996; 37: 101-113.
  • Mommers EC, van Diest PJ, Leonhart AM, Meijer CJ, Baak JP. Balance of cell proliferation and apoptosis in breast carcinogenesis. Breast Cancer Res Treat 1999; 58(2): 163-169.
  • Larsen MS, Bjerre K, Giobbie-Hurder A, ve ark. Prognostic value of Bcl-2 in two independent populations of estrogen receptor positive breast cancer patients treated with adjuvant endocrine therapy. Acta Oncol. 2012 Jul; 51(6): 781-789.
  • Kushlinskii NE, Orinovskii MB, Gurevich LE, ve ark. Expression of biomolecular markers (Ki-67, PCNA, Bcl-2, BAX, BclX, VEGF) in breast tumors. B Exp Biol Med 2004; 137(2): 182-185.
  • Tunon G, Ricote M, Ruiz A, Fraile B, Paniagua R, Royuela M. Cell cycle control related proteins (p53, p21, and Rb) and transforming growth factor B (TGFB) in benign and carcinomatous (in situ and infilrating) human breast: implications in malignant transformations. Cancer Invest 2006; 24: 119-125.
  • Tad M, Kulaçoğlu S. Memenin Duktal Karsinoma İn Situ Lezyonları: Histopatolojik Özellikler ile p53, HER2/neu, bcl-2 ve PCNA Ekspresyonu Arasındaki İlişki. Dicle Med J 2018; 45(3): 265-273.
  • Chaisson K, Rivere A, Corsetti R, Weiss T, Fuhrman GM. A potential additional variables to consider in the surgical treatment of ductal carcinoma in situ. Ochsner J 2017 Winter; 17(4): 341-344.

Memenin duktal karsinoma in situ lezyonlarında P53, HER2/neu, Bcl-2 ve PCNA ekspresyonu ve bunların invaziv karsinoma progresyonda rolleri

Yıl 2019, Cilt: 11 Sayı: 4, 490 - 496, 01.12.2019
https://doi.org/10.21601/ortadogutipdergisi.536772

Öz

Amaç: Proliferatif aktivitenin, onkogenlerde ve tümör süpresör genlerdeki değişikliklerin anlaşılması, duktal karsinoma in situnun invaziv meme kanserine gelişme ihtimalinin yüksek olduğu olguları belirlemede önemli olabilir. Bu çalışmada p53, HER2/neu, bcl-2 ve PCNA overekspresyonunun duktal karsinoma in situnun progresyonu ile ilişkisi değerlendirildi.
Gereç ve Yöntem: Biz 20 duktal karsinoma in situ (grup 1) ve 20 invaziv duktal karsinoma birlikteliğinde duktal karsinoma in situ (grup 2) olgusunu değerlendirdik. Olgulara immünhistokimyasal yöntemler kullanılarak p53, HER2/neu, bcl-2 ve PCNA çalışıldı.
Bulgular: Grup 2 olgularında p53, HER2/neu ve PCNA overekspresyonu daha yüksekti. Ancak farklar istatistiksel olarak anlamlı değildi (p>0,05). Grup 1 olgularının %36,8’inde, grup 2 olgularının %70’inde bcl-2 overekspresyonu izlendi. İki grup arasındaki bu fark istatistiksel olarak anlamlıydı (p<0,05). Çalışmamızda önemli bulgulardan biri de, p53, HER2/neu, bcl-2 ve PCNA overekspresyonunun aynı anda grup 2 olgularının 3’ünde izlenirken grup 1 olgularının hiçbirinde gözlenmemesiydi.
Sonuç: Bulgular bize, bcl-2 overekspresyonunun duktal karsinoma in situnun invaziv duktal karsinomaya gelişim ihtimalinin yüksek olduğu olguları belirlemede daha değerli olabileceğini, invaziv duktal karsinoma gelişiminde farklı progresyon yollarının varolduğunu, preinvaziv evrede bu değişikliklerin birden fazlasının aynı olguda tespit edilmesinin invaziv duktal karsinomaya progresyon riskini belirlemede tek başlarına olduğundan daha değerli olabileceğini gösterdi. Bu sonuçlar farklı biyolojik davranışa sahip DKIS alt tiplerinin tanımlanmasına katkı sağlayacaktır.

Kaynakça

  • Mercier I, Gonzales DM, Quann K, ve ark. CAPER, a novel regulator of human breast cancer progression. Cell Cycle 2014 Apr 15; 13(8): 1256-1264.
  • Perez AA, Balabram D, Salles MA, Gobbi H. Ductal carcinoma in situ of the breast: correlation between histopathological features and age of the patients. Diagn Pathol. 2014; 9: 227-232.
  • Terry G, Ho L, Londesborough P, Duggan C, Hanby A, Cuzick J. The expression of FHIT, PCNA and EGFR in benign and malignant breast lesions. Br J Cancer 2007 Jan 15; 96(1): 110-117.
  • Tot T. DCIS, cytokeratins and the theory of the sick lobe. Virchows Arch 2005; 447: 1-8.
  • Gerber B, Müller H, Reimer T, Krause A, Friese K. Nutrition and lifestyle factors on the risk of developing breast cancer. Breast Cancer Res Treat 2003; 79(2): 265-276.
  • Gerber B, Mylonas I. Reduction of the risk of breast cancer. Zentralbl Gynecol 2003; 125(1): 6-16.
  • Pape-Zambito D, Jiang Z, Wu H, ve ark. Identifying a Highly-Aggressive DCIS Subgroups by Studying Intra-Individual DCIS Heterogeneity among Invasive Breast Cancer Patients. PLoS One. 2014; 9(6): e100488.
  • Shang M, Zhang X, Liu X, ve ark. P16 and P53 Play Distinct Poles in Different Subtypes of Breast Cancer. PLoS One. 2013; 8(10): e76408.
  • Menard S, Fortis S, Castiglioni F, Agresti R, Balsari A. HER-2 as a prognostic factor in breast cancer. Oncol 2001; 61: 67-72.
  • Barlett JMS, Nofech-Moses S, Rakovitch E. Ductal carcinoma in situ of the breast: can biomarkers improve current management. Clin Chem 2014; 60(1): 60-67.
  • Siziopikou KP, Khan S. Correlation of HER-2 gene amplification with expression of the apoptosis-suppressing genes bcl-2 and bcl-x-L in ductal carcinoma in situ of the breast. Appl Immunohistochem Mol Morphol 2005; 13: 14-18.
  • Keohavong P, Gao WM, Mady HH, Kanbour-Shakir A, Melhem MF. Analysis of p53 mutations in cells taken from paraffin-embedded tisue sections of ductal carcinoma in situ and atypical ductal hyperplasia of the breast. Cancer Lett 2004; 212(1): 121-130.
  • Mylonas I, Makovitzky J, Jeschke U, Briese V, Friese K, Gerber B. Expression of Her2/neu, Steroid Receptors (ER and PR), Ki-67, and p53 in Invasive Mammary Ductal Carcinoma Associated with Ductal Cacinoma In Situ (DCIS) Versus Invasive Breast Cancer Alone. Anticancer Res 2005; 25: 1719-1724.
  • Mommers ECM, Leonhart AM, Falix F, Michalides R, Meijer CJLM, Baak JP. Similarity in expression of cell cycle proteins between in situ and invasive ductal breast lesions of same differantiation grade. J Pathol 2001; 194: 327-333.
  • Mommers ECM, Van Diest PJ, Leonhart AM, Meijer CJLM, Baak JPA. Expression of proliferation and apoptosis-related proteins in usual ductal hyperplasia of the breast. Hum Pathol 1998; 29: 1539-1545.
  • Allred DC, Clark GM, Molina R, ve ark. Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. Hum Pathol 1992; 23(9): 974-979.
  • Umekita Y, Takasaki T, Yoshida H. Expression of p53 protein in benign epithelial hyperplasia, atypical ductal hyperplasia, noninvasive and invasive mammary carcinoma. An immunohistochemical study. Virchows Arch 1994; 424(5): 491-494.
  • Hung MC, Lau YK. Basic science of HER-2/neu: a review. Semin Oncol 1999; 26: 51-59.
  • Roetger A, Merschjann A, Dittmar T, Jackisch C, Barnekow A, Brandt B. Selection of potentially metastatic subpopulations expressing c-erbB-2 from breast cancer tissue by use of an extravasation model. Am J Pathol 1998; 153: 1797-1806.
  • Hockenbery DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ. Bcl-2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci U S A 1991; 88: 6961-6965.
  • Stewart BW. Mechanisms of apoptosis: integration of genetic, biochemical, and cellular indicators. J Natl Cancer Inst 1994; 86(17): 1286-1296.
  • Siziopikou KP, Prioleau JE, Harris JR, Schnitt SJ. Bcl-2 expression in the spectrum of preinvasive breast lesions. Cancer 1996; 77: 499-506.
  • Sizopikou KP, Schnitt SJ. MIB-1 proliferation index in ductal carcinoma in situ of the breast: relationship to the expression of the apoptosis-regulating proteins bcl-2 and p53. Breast J 2000; 6(6): 400-406.
  • Niewiadomska H, Jeziorski A, Olborski B. The expression of the proliferating antigen Ki67, PCNA and products of gene p53 in primary invasive ductal breast carcinoma. J Exp Clin Cancer Res 1998; 17(4): 503-510.
  • Haerslev T, Jacobsen GK, Zedeler K. Correlation of growth fraction by Ki-67 and proliferating cell nuclear antigen (PCNA) immunohistochemistry with histopathological parameters and prognosis in primary breast carcinomas. Breast Cancer Res Treat 1996; 37: 101-113.
  • Mommers EC, van Diest PJ, Leonhart AM, Meijer CJ, Baak JP. Balance of cell proliferation and apoptosis in breast carcinogenesis. Breast Cancer Res Treat 1999; 58(2): 163-169.
  • Larsen MS, Bjerre K, Giobbie-Hurder A, ve ark. Prognostic value of Bcl-2 in two independent populations of estrogen receptor positive breast cancer patients treated with adjuvant endocrine therapy. Acta Oncol. 2012 Jul; 51(6): 781-789.
  • Kushlinskii NE, Orinovskii MB, Gurevich LE, ve ark. Expression of biomolecular markers (Ki-67, PCNA, Bcl-2, BAX, BclX, VEGF) in breast tumors. B Exp Biol Med 2004; 137(2): 182-185.
  • Tunon G, Ricote M, Ruiz A, Fraile B, Paniagua R, Royuela M. Cell cycle control related proteins (p53, p21, and Rb) and transforming growth factor B (TGFB) in benign and carcinomatous (in situ and infilrating) human breast: implications in malignant transformations. Cancer Invest 2006; 24: 119-125.
  • Tad M, Kulaçoğlu S. Memenin Duktal Karsinoma İn Situ Lezyonları: Histopatolojik Özellikler ile p53, HER2/neu, bcl-2 ve PCNA Ekspresyonu Arasındaki İlişki. Dicle Med J 2018; 45(3): 265-273.
  • Chaisson K, Rivere A, Corsetti R, Weiss T, Fuhrman GM. A potential additional variables to consider in the surgical treatment of ductal carcinoma in situ. Ochsner J 2017 Winter; 17(4): 341-344.
Toplam 31 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma makaleleri
Yazarlar

Murat Tad 0000-0003-2772-5856

Sezer Kulaçoğlu Bu kişi benim 0000-0003-3288-2039

Yayımlanma Tarihi 1 Aralık 2019
Yayımlandığı Sayı Yıl 2019 Cilt: 11 Sayı: 4

Kaynak Göster

Vancouver Tad M, Kulaçoğlu S. Memenin duktal karsinoma in situ lezyonlarında P53, HER2/neu, Bcl-2 ve PCNA ekspresyonu ve bunların invaziv karsinoma progresyonda rolleri. otd. 2019;11(4):490-6.

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