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The correlation with prognostic factors of bcl-2 and cathepsin D in invasive ductal carcinomas

Yıl 2018, Cilt: 2 Sayı: 3, 186 - 218, 12.11.2018

Öz

Introduction: Invasive ductal carcinoma which
is cancers of the breast is the most common cancer of the breast in women. In this
tumors, early diagnosis and appropriate medical treatment is to influence
markedly to life span. For this reason, cancers of the breast is occured
intesify at therapy with chemotherapotic agents and hormonal treatment for the
purpose of prevention systemic spread and prognosis determination of works in
the last years. Just reliable determinatives are necessary, because of not to
be adequate to orientate treatment and prognosis only classıc parameters. For
this reason, it was evaluated the correlation with each other and other
prognostic factors of bcl-2 and cathepsin D in invasive ductal carcinomas of
the breast in the present study.

Materials and methods: In the present study. it
was included 50 cases diagnosed with invasive ductal carcinoma and examined
mastectomy and axillary dissection material. Slides stained  with estrogen, progesterone and c-erbB-2 were
reviewed again and done scoring separately for each slide.Also in the present
study it was stained bcl-2 and cathepsin D expression in 50 invasive ductal
carcinomas by immünhistochemistry, and evaluated the correlation with other
prognostic factors and each other.

Results: A strong positive relationship was not
detected between bcl-2 expression with other prognostic factors and cathepsin D
protein, while a strong positive relationship was detected between bcl-2
expression with low nuclear grade and progesterone receptor’ status. A strong
correlation was not observed between cathepsin D expression with oestrogen
receptor’ status and progesterone receptor’ status and c-erbB-2 oncogene
amplification and other prognostic factors, while a strong correlation was also
observed between cathepsin D expression with high nuclear grade and blood
vessel invasion and lymph-vessel invasion and perineural invasion.







Conclusion: Bcl-2 is thought to be important in
determining of invasive ductal carcinoma cases with low grade, while cathepsin
D is thought to be important in determining of invasive ductal carcinoma cases
with high grade and invasion ability. 

Kaynakça

  • 1. Gewefel H, Salhia B. Breast cancer in adolescent and young adult women. Clin Breast Cancer. 2014; 14(6): 390-5.2. Rezaianzadeh A, Sepandi M, Akrami M, Tabatabaee H, Rajaeefard A, Tahmasebi S, et al. Pathological profile of patients with breast diseases in Shiraz. Asian Pac J Cancer Prev. 2014; 15(19): 8191-5.3. Tao Z, Shi A, Lu C, Song T, Zhang Z, Zhao J. Breast Cancer: Epidemiology and Etiology.Cell Biochem Biophys. 2015; 72(2): 333-8.4. Verma R, Bowen RL, Slater SE, Mihaimeed F, Jones JL. Pathological and epidemiological factors associated with advanced stage at diagnosis of breast cancer. Br Med Bull. 2012; 103(1): 129-45.5. Gasparini G, Barbarechi M, Doglioni C. Exp of bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer. Clin Cancer Res. 1995; 1(2): 189-98.6. Nakopoulou L, Michalopoulou A, Giannopoulou I, Tzonou A, Keramopoulos A, Lazaris AC, et al. bcl-2 protein expression is associated with a prognostically favorable phenotype in breast cancer irrespective of p53 immunostaining. Histopathology 1999; 34(4): 310-19.7. Winstanley JH, Leinster SJ, Cooke TG, Westley BR, Platt-Higgins AM, Rudland PS. Prognostic significance of cathepsin D in patients with breast cancer. Br J Cancer 1993; 67(4): 767-72.8. Nadji M, Fresno M, Nassiri M, Conner G, Herrero A, Morales AR. Cathepsin D in host stromal cells, but not in tumor cells, is associated with aggressive behaviour in node-negative breast cancer. Hum. Pathol. 1996; 27(9); 890-95.9. Contesso G, Jotti GS. Bonadonna G.: Tumor grade as a prognostic factor in primary breast cancer. Eur J Clin Oncol. 1989; 25(3): 403-9.10. Pradhan SP, Dash A, Choudhury S, Mishra DP. Robinson's cytological grading on aspirates of breast carcinoma and correlation with Bloom-Richardson's histological grading. J Evid Based Med Healthcare.2017; 4(2): 86-91.11. De Potter CR, Schelfhout AM. The neu-protein and breast cancer. Wirchows Arch 1995; 426(2): 107-15.12. Razumovic JJ, Petrovecki M, Uzarevic B, Gamulin S. Mutual predictive value of c-erbB-2 overexpression and various prognostic factors in ductal invasive breast carcinoma. Tumori 2000; 86(1): 30-6.13. Howard EM, Lau SK, Lyles RH, Birdsong GG, Tadros TS, Umbreit JN, et al. Correlation and expression of p53, Her-2, vascular endothelial growth factor (VEGF), and e-cadherin in a high-risk breast cancer population. Int J Clin Oncol. 2004; 9(3): 154-60.14. Kariya S, Ogawa Y, Nishioka A, Moriki T, Ohnishi T, Ito S, et al. Relationship between hormonal receptors, HER-2, p53 protein, Bcl-2, and MIB-1 status and the antitumor effects of neoadjuvant anthracycline-based chemotherapy in invasive breast cancer patients. Radiat Med 2005; 23(3): 189-94.15. Chintamani, Singhal V, Singh JP, Lyall A, Saxena S, Bansal A. Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? –A prospective clinical study. BMC Cancer 2004; 4: 48-57.16. Zhang GJ, Kimijima I, Abe R, Kanno M, Katagata N, Hara K, et al. Correlation between the expression of apoptosis related bcl-2 and p53 oncoproteins and the carcinogenesis and progression of breast carcinomas. Clin Cancer Res 1997;3(12): 2329-35.17. Zhang GJ, Kimijima I, Tsuchiya A, Abe R. The role of bcl-2 expression in breast carcinomas. Oncol Rep. 1998; 5(5): 1211-16.18. Quinn CM, Ostrowski JL, Harkins L, Rice AJ, Loney DP. Loss of bcl-2 expression in ductal carcinoma in situ of the breast relates to poor histological differantiation and to expression of p53 and c-erbB-2 proteins. Histopathology 1998; 33(6): 531-6.19. Takei H, Oyama T, Iino Y, Horiguchi J, Hikino T, Maemura M, et al. Clinical significance of immunohistochemical bcl-2 expression in invasive breast carcinoma. Oncol Rep. 1999; 6(3): 575-81.20. Zhang GJ, Tsuda H, Adachi I, Fukutomi T, Yamamoto H, Hirohashi S, et al. Prognostic indicators for breast cancer patients with one to three regional lymph node metastasis with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 protein. Jpn J Clin Oncol. 1997; 27(6): 371-7.21. Eissa S, Labib R, Khalifa A, Swelam N, Khalil F, El-Shenawy AM. Regulator of apoptosis in human breast cancer. Clin Biochem. 1999; 32(5): 321-6.22. Hellemans P, van Dam PA, Weyler J, van Oosterom AT, Buytaert P, Van Marck E. Prognostic value of bcl-2 expression in invasive breast carcinoma. Br J Cancer 1995; 72(2): 354-60.23. Texeira C, Reed JC, Pratt MAC. Estrogen promotes chemotherapeutic drug resistance by a mechanism involving bcl-2 proto-oncogene expression in human breast cancer cells. Cancer Res. 1995; 55(17): 3902-7.24. Lee WY, Jin YT, Tzeng CC. Reciprocal expression of bcl-2 and p53 in breast ductal carcinoma. Anticancer Res 1996; 16(5A): 3007-12.25. Krajewski S, Thor AD, Edgerton SM, Moore DH 2nd, Krajewska M, Reed JC. Analysis of bax and bcl-2 expression in p53 immunopositive breast cancers. Clin Cancer Res. 1997; 3(2): 199-208.26. Brouillet JP, Theillet C, Maudelonde T, Defrenne A, Simony-Lafontaine J, Sertour J, et al. Cathepsin D assay in primary breast cancer and lymph nodes: relationship with c-myc, c-erb-B-2 and int-2 oncogene amplification and node invasiveness. Eur J Cancer 1990; 26(4): 437-41.27. Maudelonde T, Khalaf S, Garcia M, Freiss G, Duporte J, Benatia M, et al. ,Immunoenzymatic assay of Mr 52.000 cathepsin D in 182 breast cancer cytosols: low correlation with other prognostic parameters. Cancer Res. 1988; 48(2): 462-6. 28. Thorpe SM, Rochefort H, Garcia M, Freiss G, Christensen IJ, Khalaf S, et al. Association between high concentrations of Mr 52.000 cathepsin D and poor prognosis İn primary human breast cancer. Cancer Res. 1989; 49(21): 6008-14.29. Henry JA, McCarthy AL, Angus B, Westley BR, May FE, Nicholson S, et al. Prognostic significance of the estrogen-regulated protein cathepsin D in breast cancer. An immunohistochemical study. Cancer 1990; 65(2): 265-71.30. Kandalaft PL, Chang KL, Ahn CW, Traweek ST, Mehta P, Battifora H. Prognostic significance of immunohistochemical analysis of cathepsin D in low stage breast cancer. Cancer 1993; 71(9): 2756-63. 31. Hurlimann J, Gebhard S, Gomez F. Oestrogen receptor, progestrone receptor, pS2, ERD5, HSP 27 and cathepsin-D in invasive ductal breast carcinomas. Histopathology 1993; 23(3): 239-48.32. Armas OA, Gerald WL, Lesser ML, Arroyo CD, Norton L, Rosen PP. Immunohistochemical detection of cathepsin D in T2N0 M0 breast carcinoma. Am J Surg Pathol. 1994; 18(2): 158-66.33. Okamura K, Kobayashi I, Matsuo K, Kiyoshima T, Yamamoto K, Miyoshi A, et al. Immunohistochemical localization of cathepsin D, proliferating cell nuclear antigen and epidermal growth factor receptor in human breast carcinoma analysed by computer image analyser:correlation with histological grade and metastatic behaviour. Histopathology 1997; 31(6): 540-8.34. Domagala W, Striker G, Szadowska A, Dukowicz A, Weber K, Osborn M. Cathepsin D in invasive ductal NOS breast carcinoma as defined by immunohistochemistry. No correlation with survival at 5 years. Am J Pathol. 1992; 141(5): 1003-12.

İnvaziv duktal karsinomlarda bcl 2 ve katepsin D’nin prognostik faktörlerle ilişkisi

Yıl 2018, Cilt: 2 Sayı: 3, 186 - 218, 12.11.2018

Öz

GİRİŞ



Meme
kanserlerinden invaziv duktal karsinom, kadınlarda en sık görülen meme
kanseridir. Bu tümörlerde erken tanı ve uygun tedavi yaşam süresini önemli
ölçüde etkilemektedir. Bu nedenle son yıllardaki çalışmaların, meme kanserlerinde prognozu belirleme ve sistemik
yayılımı önleme amacıyla hormonal
ve kemoterapötik ajanlarla tedavide
yoğunlaştığı görülmektedir. Sadece klasik parametrelerin prognozu ve tedaviyi
yönlendirmede yeterli olmaması nedeniyle yeni, güvenilir belirleyicilere gerek
vardır. Bu nedenle bu çalışmada, memenin
invaziv duktal karsinom (İDK)’unda bcl-2 ve katepsin D’nin birbirleriyle ve
diğer prognostik faktörlerle
olan
ilişkisi araştırıldı.



GEREÇ VE YÖNTEM



2004-2006 yılları
arasında Yüzüncü Yıl Üniversitesi Tıp Fakültesi Patoloji Ana Bilim Dalında
mastektomi ve aksiller diseksiyon materyali incelenen ve invaziv duktal
karsinom tanısı alan 50
adet olgu çalışmaya alındı.
Bu
olguların tümör diferansiyasyonu, histolojik derece ve nükleer skor (NS)’ları ile
mitoz sayısı Bloom Richardson'a göre ayrı ayrı değerlendirildi.
Bunun yanısıra tümör çevresi lenfatik, kan damarı
ve perinöral invazyonun varlığı
araştırıldı.
Tümörün deri ile ilişkisi saptandı.

Tümör çapı ve aksiller lenf nodlarının durumu değerlendirildi. Multifokal ve
multisentrik
tümörlerde, en büyük
tümörün çapı ele alındı. Östrojen, progesteron ve c-erbB-2 ile boyanmış olan
lamlar tekrar gözden geçirilerek her biri için ayrı ayrı skorlama yapıldı.



Ayrıca 50 invaziv duktal
karsinom olgusu, bcl-2 ve katepsin D ile immünhistokimyasal olarak boyandı ve
her biri için ayrı ayrı skorlama yapılarak sonuçlar birbirleri ve diğer
prognostik faktörlerle karşılaştırılarak değerlendirildi.



BULGULAR



Progesteron reseptörü ve
düşük NS ile bcl-2 ekspresyonu arasında güçlü pozitif bir ilişki tespit
edilirken katepsin D ve diğer prognostik faktörlerle bcl-2 ekspresyonu arasında
güçlü pozitif bir ilişki tespit edilmedi. Perinöral invazyon, lenf damarı
invazyonu, kan damarı invazyonu ve yüksek NS ile katepsin D ekspresyonu
arasında güçlü pozitif bir ilişki gözlenirken diğer prognostik faktörler,
c-erbB2, progesteron reseptörü, östrojen reseptörü ile katepsin D ekspresyonu
arasında güçlü bir ilişki gözlenmedi.



SONUÇ



Bcl-2’nin düşük dereceli, katepsin D’nin ise yüksek dereceli ve
invazyon yeteneği kazanmış invaziv duktal karsinom olgularının
belirlenmesinde önemli
olabileceği düşünülmektedir.

Kaynakça

  • 1. Gewefel H, Salhia B. Breast cancer in adolescent and young adult women. Clin Breast Cancer. 2014; 14(6): 390-5.2. Rezaianzadeh A, Sepandi M, Akrami M, Tabatabaee H, Rajaeefard A, Tahmasebi S, et al. Pathological profile of patients with breast diseases in Shiraz. Asian Pac J Cancer Prev. 2014; 15(19): 8191-5.3. Tao Z, Shi A, Lu C, Song T, Zhang Z, Zhao J. Breast Cancer: Epidemiology and Etiology.Cell Biochem Biophys. 2015; 72(2): 333-8.4. Verma R, Bowen RL, Slater SE, Mihaimeed F, Jones JL. Pathological and epidemiological factors associated with advanced stage at diagnosis of breast cancer. Br Med Bull. 2012; 103(1): 129-45.5. Gasparini G, Barbarechi M, Doglioni C. Exp of bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer. Clin Cancer Res. 1995; 1(2): 189-98.6. Nakopoulou L, Michalopoulou A, Giannopoulou I, Tzonou A, Keramopoulos A, Lazaris AC, et al. bcl-2 protein expression is associated with a prognostically favorable phenotype in breast cancer irrespective of p53 immunostaining. Histopathology 1999; 34(4): 310-19.7. Winstanley JH, Leinster SJ, Cooke TG, Westley BR, Platt-Higgins AM, Rudland PS. Prognostic significance of cathepsin D in patients with breast cancer. Br J Cancer 1993; 67(4): 767-72.8. Nadji M, Fresno M, Nassiri M, Conner G, Herrero A, Morales AR. Cathepsin D in host stromal cells, but not in tumor cells, is associated with aggressive behaviour in node-negative breast cancer. Hum. Pathol. 1996; 27(9); 890-95.9. Contesso G, Jotti GS. Bonadonna G.: Tumor grade as a prognostic factor in primary breast cancer. Eur J Clin Oncol. 1989; 25(3): 403-9.10. Pradhan SP, Dash A, Choudhury S, Mishra DP. Robinson's cytological grading on aspirates of breast carcinoma and correlation with Bloom-Richardson's histological grading. J Evid Based Med Healthcare.2017; 4(2): 86-91.11. De Potter CR, Schelfhout AM. The neu-protein and breast cancer. Wirchows Arch 1995; 426(2): 107-15.12. Razumovic JJ, Petrovecki M, Uzarevic B, Gamulin S. Mutual predictive value of c-erbB-2 overexpression and various prognostic factors in ductal invasive breast carcinoma. Tumori 2000; 86(1): 30-6.13. Howard EM, Lau SK, Lyles RH, Birdsong GG, Tadros TS, Umbreit JN, et al. Correlation and expression of p53, Her-2, vascular endothelial growth factor (VEGF), and e-cadherin in a high-risk breast cancer population. Int J Clin Oncol. 2004; 9(3): 154-60.14. Kariya S, Ogawa Y, Nishioka A, Moriki T, Ohnishi T, Ito S, et al. Relationship between hormonal receptors, HER-2, p53 protein, Bcl-2, and MIB-1 status and the antitumor effects of neoadjuvant anthracycline-based chemotherapy in invasive breast cancer patients. Radiat Med 2005; 23(3): 189-94.15. Chintamani, Singhal V, Singh JP, Lyall A, Saxena S, Bansal A. Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? –A prospective clinical study. BMC Cancer 2004; 4: 48-57.16. Zhang GJ, Kimijima I, Abe R, Kanno M, Katagata N, Hara K, et al. Correlation between the expression of apoptosis related bcl-2 and p53 oncoproteins and the carcinogenesis and progression of breast carcinomas. Clin Cancer Res 1997;3(12): 2329-35.17. Zhang GJ, Kimijima I, Tsuchiya A, Abe R. The role of bcl-2 expression in breast carcinomas. Oncol Rep. 1998; 5(5): 1211-16.18. Quinn CM, Ostrowski JL, Harkins L, Rice AJ, Loney DP. Loss of bcl-2 expression in ductal carcinoma in situ of the breast relates to poor histological differantiation and to expression of p53 and c-erbB-2 proteins. Histopathology 1998; 33(6): 531-6.19. Takei H, Oyama T, Iino Y, Horiguchi J, Hikino T, Maemura M, et al. Clinical significance of immunohistochemical bcl-2 expression in invasive breast carcinoma. Oncol Rep. 1999; 6(3): 575-81.20. Zhang GJ, Tsuda H, Adachi I, Fukutomi T, Yamamoto H, Hirohashi S, et al. Prognostic indicators for breast cancer patients with one to three regional lymph node metastasis with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 protein. Jpn J Clin Oncol. 1997; 27(6): 371-7.21. Eissa S, Labib R, Khalifa A, Swelam N, Khalil F, El-Shenawy AM. Regulator of apoptosis in human breast cancer. Clin Biochem. 1999; 32(5): 321-6.22. Hellemans P, van Dam PA, Weyler J, van Oosterom AT, Buytaert P, Van Marck E. Prognostic value of bcl-2 expression in invasive breast carcinoma. Br J Cancer 1995; 72(2): 354-60.23. Texeira C, Reed JC, Pratt MAC. Estrogen promotes chemotherapeutic drug resistance by a mechanism involving bcl-2 proto-oncogene expression in human breast cancer cells. Cancer Res. 1995; 55(17): 3902-7.24. Lee WY, Jin YT, Tzeng CC. Reciprocal expression of bcl-2 and p53 in breast ductal carcinoma. Anticancer Res 1996; 16(5A): 3007-12.25. Krajewski S, Thor AD, Edgerton SM, Moore DH 2nd, Krajewska M, Reed JC. Analysis of bax and bcl-2 expression in p53 immunopositive breast cancers. Clin Cancer Res. 1997; 3(2): 199-208.26. Brouillet JP, Theillet C, Maudelonde T, Defrenne A, Simony-Lafontaine J, Sertour J, et al. Cathepsin D assay in primary breast cancer and lymph nodes: relationship with c-myc, c-erb-B-2 and int-2 oncogene amplification and node invasiveness. Eur J Cancer 1990; 26(4): 437-41.27. Maudelonde T, Khalaf S, Garcia M, Freiss G, Duporte J, Benatia M, et al. ,Immunoenzymatic assay of Mr 52.000 cathepsin D in 182 breast cancer cytosols: low correlation with other prognostic parameters. Cancer Res. 1988; 48(2): 462-6. 28. Thorpe SM, Rochefort H, Garcia M, Freiss G, Christensen IJ, Khalaf S, et al. Association between high concentrations of Mr 52.000 cathepsin D and poor prognosis İn primary human breast cancer. Cancer Res. 1989; 49(21): 6008-14.29. Henry JA, McCarthy AL, Angus B, Westley BR, May FE, Nicholson S, et al. Prognostic significance of the estrogen-regulated protein cathepsin D in breast cancer. An immunohistochemical study. Cancer 1990; 65(2): 265-71.30. Kandalaft PL, Chang KL, Ahn CW, Traweek ST, Mehta P, Battifora H. Prognostic significance of immunohistochemical analysis of cathepsin D in low stage breast cancer. Cancer 1993; 71(9): 2756-63. 31. Hurlimann J, Gebhard S, Gomez F. Oestrogen receptor, progestrone receptor, pS2, ERD5, HSP 27 and cathepsin-D in invasive ductal breast carcinomas. Histopathology 1993; 23(3): 239-48.32. Armas OA, Gerald WL, Lesser ML, Arroyo CD, Norton L, Rosen PP. Immunohistochemical detection of cathepsin D in T2N0 M0 breast carcinoma. Am J Surg Pathol. 1994; 18(2): 158-66.33. Okamura K, Kobayashi I, Matsuo K, Kiyoshima T, Yamamoto K, Miyoshi A, et al. Immunohistochemical localization of cathepsin D, proliferating cell nuclear antigen and epidermal growth factor receptor in human breast carcinoma analysed by computer image analyser:correlation with histological grade and metastatic behaviour. Histopathology 1997; 31(6): 540-8.34. Domagala W, Striker G, Szadowska A, Dukowicz A, Weber K, Osborn M. Cathepsin D in invasive ductal NOS breast carcinoma as defined by immunohistochemistry. No correlation with survival at 5 years. Am J Pathol. 1992; 141(5): 1003-12.
Toplam 1 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Klinik Tıp Bilimleri
Bölüm ARAŞTIRMA MAKALESİ
Yazarlar

Mustafa Kösem Bu kişi benim

İbrahim Gelincik

İrfan Bayram

Mehmet Çetin Kotan Bu kişi benim

Ayhan Yıldırım Bu kişi benim

Yayımlanma Tarihi 12 Kasım 2018
Yayımlandığı Sayı Yıl 2018 Cilt: 2 Sayı: 3

Kaynak Göster

APA Kösem, M., Gelincik, İ., Bayram, İ., Kotan, M. Ç., vd. (2018). İnvaziv duktal karsinomlarda bcl 2 ve katepsin D’nin prognostik faktörlerle ilişkisi. Balıkesir Medical Journal, 2(3), 186-218.