To evaluate the correlation of p53 and Bcl-2, expressions with c-erbB-2, estrogen and progesterone receptors in breast carcinoma

Year 2006, Volume: 37 Issue: 4, 89 - 94, 01.05.2006

Sevinç Hallaç Keser Nimet Karadayı Mine Çayırcı Hakan Karabulut Sibel Şensu

Abstract

OBJECTIVES: Several studies have established the functional markers that play role in human breast carcinomas and help the activities of anticancer agents. Although the treatment modalities of mammary carcinomas are chosen by evaluating prognostic parameters, none of the molecular markers has yet been accepted as an independent prognostic factor. However, recently, p53 tumour supressor gene and bcl-2 protooncogene have gained increasing interest. As well as estrogen receptor (ER) protein, progesterone receptor (PR) protein and c-erbB-2 levels are shown to have importance in individual response to hormonotherapy, radiotherapy and chemotherapy. Approaches of combining molecular markers provide more clinicopathological criteria that result in better predictions. In this study, we aimed to investigate the relationship of p53 and bcl-2 which are rather new markers, with c-erbB-2, ER and PR proteins. METHODS: In our pathology department, 65 mammary invasive ductal carcinoma cases are investigated for p53 and bcl-2, c-erbB-2, ER and PR expressions immunohistochemically (IHC) by using HRP-AEC methods. Besides, the staining percentages and staining intensity of the cases are compared statistically. RESULTS: Forty-seven out of 65 cases (72.3%) showed positive staining by p53, bcl-2 and PR protein. Forty-five out of 65 cases (69.2%) had positive staining by ER protein and 23 (35.3%) by c-erbB-2. Results were analysed by using chi square statistical analysis. There was no statistically significant correlation between p53 and bcl-2, c-erbB-2, ER or PR protein expressions (p>0.05) and between bcl-2 and c-erbB-2, ER or PR protein expressions (P>0.05). CONCLUSION: Although each one is accepted to have value regarding prognosis, our results, in acccordance with various literatures, did not show any statistically significant correlation between neither p53 nor bcl-2 and the selected prognostic parameters.

Keywords

Breast Neoplasms, Tumor Suppressor Protein p53, Genes, bcl-2, Proto-Oncogene Proteins c-bcl-2, Estrogens, Progesterone, Genes, erbB-2, Oncogene Proteins v-erbB

Meme karsinomlarında P53 ve Bcl-2 ekspresyonlarının c-erb, B-2 östrojen ve progesteron reseptörleriyle ilişkinin değerlendirilmesi

Abstract

Bazı çalışmalar insan meme karsinomlarmda rol oynayan ve antikanser ajanlarının aktivitelerine yardım eden fonksiyonel işaretleyicilerin (marker) varlığını ortaya koymuştur. Prognostik parametreler değerlendirilerek seçilmiş olan meme karsinomlarının tedavi modalitelerine rağmen, moleküler marker 'ların hiçbiri henüz bağımsız bir prognostik faktör olarak kabul edilmemiştir. Bununla birlikte, son zamanlarda, p53 tümör supresör gen proteini ve bcl-2 protoonkogeni giderek artan önem kazanmışlardır. Ostrojen (ER) kadar, progesteron reseptör proteini (PR) ve c-erbB-2 seviyeleri hormonoterapi, radyoterapi ve kemoterapiye bireysel yanıtta öneme sahip olduklarını göstermişlerdir. Moleküler marker'ların kombinasyonuna ilişkin yaklaşımlar,, daha iyi tahminlerle sonuçlanan daha fazla klinopatolojik kriter sağlar. Bu çalışmada, c-erb B-2, ER ve PR proteinleri ile daha yeni markerlar olan bcl-2 ve p53'üri ilişkilerini araştırmayı amaçladık. METODLAR: Patoloji bölümümüzde, 65 invasiv duktal meme karsinom vakasının p53 ve bcl-2, c-erbB-2, ER ve PR ekspresyonları HRP-AEC yöntemi kullanılarak immünohistokimyasal olarak (IHK) araştırılmıştır. Bunun yanısıra, boyanma oranları ve boyanma yoğunlukları istatistiksel olarak karşılaştırılmıştır. BULGULAR: 65 olgunun 47'si (% 72.3) p53, bcl-2 ve PR proteini ile pozitif boyanma göstermiştir. 65 vakanın 45'i (% 69.2) ER proteini ile, 23 'ü (%35.3) c-erbB-2 ile pozitif boyanmıştır. Sonuçlar ki kare istatistiki analizi kullanılarak analiz edilmişlerdir. p53 ve bcl-2, c-erbB-2, ER veya PR protein ekspresyonları arasında (p>0.05) ve bcl-2 ile c-erbB-2, ER veya PR protein ekspresyonları (p>0 05) arasında istatistiksel olarak önemli korelasyon saptanmamıştır. SONUÇ: Her birinin prognoza ilişkin değere sahip olduğu kabul edilmiş olmasına rağmen, bizim sonuçlarımızda, çeşitli literatürlere uygun olarak ne p53 ne de bcl-2 ve seçilen diğer prognostik parametreler arasında hiçbir istatistiksel öneme sahip korelasyon görülmemiştir.

Keywords

Meme neoplazmları, Tümör baskılayıcı protein p53, Genler, bcl-2, Proto-onkojen proteinler c-bcl-2, Östrojenler, Progesteron, Genler, erbB-2, Onkojen proteinler v-erbB

References

• Rosai J: Breast, Chapter 20. In: Ackerman s Surgical Pathology, ed. Rosai J., St. Louis Mosby, 2004, 9th ed: 1763-1876 Dimitrikakis C, Konstadoulakis M, Messaris E, et al. Molecular markers in breast cancer: can we use c-erbB-2, p53, bcl-2, and box gene expression as prognostic factors? The Breast 2002; 11:279-285
• Hamilton A, Piccart M. The contribution of molecular markers to the prediction of response in the treatment of breast cancer: A review of the literature on HER-2, p53 and bcl-2. Annals of Oncology 2000; 11: 647-663
• Quinn CM, Ostrowski JL, Harkins L, et al
• Loss of bcl-2 expression in ductal carcinoma in situ of the breast relates to poor histological differentiation and to expression ofp53 and c- erbB-2 proteins. Histopathology 1998; 33: 531-536
• Beenken SW, Grizzle WE, Crowe R, et al
• Molecular biomarkers for breast cancer prognosis: coexpression ofc-erbB-2 andp53
• Annals of Surgery 2001; 233: 630-638
• Pich A, Margaria E, Chiusa l. Onco genes and male breast carcinoma: c-erbB-2 andp53 coexpres sion predicts a poor survival. J Clin Oncol 2000; 18: 2948-2956
• Nakopoulou L, Michalopoulou A, Giannopoulou I, etal. Bcl-2 protein expression is associated with a prognostically favourable phenotype in breast cancer irrespective ofp53 immunostaining. Histopathology 1999; 34: 310-319
• Berardo MD, Elledge RM,de Moor C, et al
• bcl-2 and apoptosis in lymph node positive breast carcinoma. Cancer 1998; 82: 1296- 1302
• Siziopikou KP, Prioleau JE, Harris JR, et al. bcl-2 expression in the spectrum of preinvasive breast lesions. Cancer 1996, 77: 499-506
• LinjawiA, Kontogiannea M, Halwani F, et al. Prognostic significance of p53, bcl-2 and bax expression in early breast cancer. J Am Coll Surg 2004; 198: 83-90
• Gonzales AD, Hernandez MMA, Hernandez JJC, et al. Analysis of bcl-2 in sporadic breast carcinoma. Cancer 1997; 80: 2100-2108
• Arun B, Kilic G, Yen C, et al. Correlation of bcl-2 andp53 expression in primary breast tumours and corresponding metastatic lymph nodes. Cancer 2003; 98: 2554- 2559
• KrajewskiS, Thor AD, Edgerton SM, etal
• Analysis of bax and bcl-2 expression in p53- immunopositive breast cancer. Clinical Cancer Research 1997; 3:199-208
• Zhang GJ, Kimijima I, Abe R, et al
• Correlation between the expression of apopitosis-related bcl-2 andp53 oncoproteins and the carcino genesis and progression of breast carcinomas. Clinical Cancer Research 1997; 3: 2329-2335
• Bukholm IK, Nesland JM, Karesen R, et al. Interaction between bcl-2 and p21 (Waf1/C: p1) in breast carcinomas with wild-type p53
• Int J Cancer 1997; 73: 38-41
• Bozetti C, Nizzoli R, Naldi N, et al. bcl-2 expression on fine needle aspirates from primary breast carcinoma. Cancer Cytopathol 1999; 87:224-230
• Chang J, Clark GM, Allred DC, et al
• Survival of patient with metastatic breast carcinoma. Importance of prognostic markers of the primary tumour. Cancer 2003; 97:545- 553
• Haldar S, Negrini M, Monne M, et al
• Down-regulation of bcl-2 by p53 in breast cancer cells. Cancer Research 1994; 54. 2095- 2097
• Rodrigues NA, Dillon D, Carter D, et al
• Differences in the pathologic and molecular features of intraductal breast carcinoma between younger and older women. Cancer 2003; 97:1393-1403
• Mottelese M, Benevolo M, Del Monte G, et al. Role ofp53 and bcl-2 in high-risk breast cancer patients treated with adjuvant antracycline-based chemotherapy. J Cancer Res Clin Oncol 2000; 126: 722-729