Ömer ULUOĞLU, Güldal YILMAZ, Pınar GEYİK

Belirgin intraduktal komponent içeren invaziv duktal meme karsinomlarında immünhistokimyasal yöntemle araştırılan katepsin D,siklin D1 ve timidin kinaz 1 ekspresyonunun prognostik önemi

Amaç: Belirgin intraduktal komponent içeren invaziv duktal meme karsinomlarında katepsin D (KD), timidin kinaz 1 (TK1) ve siklin D1 (SD1) ekspresyonunun immünhistokimyasal yöntemle araştırılması ve prognostik öneminin belirlenmesi.Gereç ve Yöntemler: 70 olguya ait Hematoksilen-Eozin boyalı preparatlar retrospektif olarak değerlendirildi. Klinik bilgilere hasta takip dosyalarından ve hastalarla temasa geçilerek ulaşıldı. İnvaziv tümör komponentinin histopatolojik derecelendirmesinde Bloom-Richardson derecelendirmesinin Nottingham modifikasyonu kullanıldı. Evrelemede American Joint Committee on Cancer tarafından önerilen sistem kullanıldı. İstatistiksel incelemede Pearson Ki-kare,Likelihood ratio, Fisher’s exact testleri ve Kaplan-Meier yaşam çözümlemesi yöntemleri kullanıldı ve p

Prognostic significance of immunohistochemical expression of cathepsin D, cyclin D1, and thymidine kinase 1 in invasive ductal breast carcinomas with apredominant intraductal component

Aim: To evaluate the expression of cathepsin D (CD), thymidine kinase 1 (TK1), and cyclin D1 (CycD1) in invasive ductal breast carcinomas with a predominant intraductal component and to determine their prognostic value. Materials and Methods: The examination of slides stained with Haematoxylin- Eosin of 70 patients was performed retrospectively, and clinical and prognostic data were obtained. The histopathological grading of the invasive tumour component was done using the Nottingham modification of the Bloom-Richardson grading system, and staging by using the system proposed by the American Joint Committee on Cancer. Pearson’s chi-square, Likelihood ratio, Fisher’s exact tests, and Kaplan-Meier survival analysis were used as statistical tests and the significance of observed differences was set at p

PDF

___

1- Parkin DM, Bray F, Ferlay J, et al. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001; 94: 153-156.
2- Gillett C, Fantl V, Smith R, et al. Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res 1994; 54: 1812-1817.
3- Romain S, Spyratos F, Descotes F, et al. Prognostic of DNAsynthesizing enzyme activities (thymidine kinase and thymidilate synthase) in 908 T1-T2, N0-N1, M0 breast cancers: A retrospective multicenter study. Int J Cancer 2000; 67: 860-868.
4- Carson WE 3rd, Liang MI. Current immunotherapeutic strategies in breast cancer. Surg Oncol Clin N Am 2007; 16: 841-860.
5- McArthur HL, Hudis CA. Breast cancer chemotherapy. Cancer J 2007; 13: 141-147.
6- Ferrandina G, Scambia G, Bardelli F, et al. Relationship between cathepsin D content and disease-free survival in node-negative breast cancer patients: a meta-analysis. Br J Cancer 1997; 76: 661-666.
7- Rochefort H. Biological and clinical significance of cathepsin D in breast cancer. Acta Oncol 1992; 31: 125-130.
8- Greco S, Marsigliante S, Leo G, et al. Co-expression of thymidine kinase and cathepsin D in 200 primary breast carcinomas. Cancer Letters 2000; 160: 13-19.
9- Hengstschläger M, Knöfler M, Müllner EW, et al. Different regulation of thymidine kinase during the cell cycle of normal versus DNA tumor virus-transformed cells. J Biol Chem 1994; 269: 13836-13842.
10- Sherr CJ. G1 phase progression: cycling on cue. Cell 1994; 79: 551-555.
11- Broët P, Romain S, Daver A, et al. Thymidine kinase as a proliferative marker: Clinical relevance in 1,692 primary breast cancer patients. J Clin Oncol 2001; 19: 2778-2787.
12- Otterbach F, Bankfalvi A, Bergner S, et al. Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast. Histopathology 2000; 37: 232-240.
13- Baldin V, Lukas J, Marcote MJ, et al. Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev 1993; 7: 812-821.
14- Shoker BS, Sloane JP. DCIS grading schemes and clinical implications. Histopathology 1999; 35: 393-400.
15- Sobin LH. Histological Typing of Breast Tumours. 2nd ed. World Health Organization, Geneva, 1981.
16- Connolly JL, Fechner RE, Kempson RL, et al. Recommendations for the reporting of breast carcinoma. Hum Pathol 1996; 27: 220-224.
17- Armas OA, Gerald WL, Lesser ML, et al. Immunohistochemical detection of cathepsin D in T2N0M0 breast carcinoma. Am J Surg Pathol 1994; 18: 158-166.
18- Marsh KL, Varley JM. Frequent alterations of cell cycle regulators in early-stage breast lesions as detected by immunohistochemistry. Br J Cancer 1998; 77: 1460-1468.
19- Gillett CE, Lee AHS, Millis RR, et al. Cyclin D1 and associated proteins in mammary ductal carcinoma in situ and atypical ductal hyperplasia. J Pathol 1998; 184: 395-400.
20- Westley B, Rochefort H. Estradiol induced proteins in the MCF7 human breast cancer cell line. Biochem Biophys Res Commun 1979;90: 410-416.
21- Foekens JA, Look MP, Bolt-de Vries J, et al. Cathepsin-D in primary breast cancer: Prognostic evaluation involving 2810 patients. Br J Cancer 1999; 79: 300-307.
22- Robertson JFR, O’Neill KL, Thomas MW, et al. Thymidine kinase in breast cancer. Br J Cancer 1990; 62: 663-667.
23- Duffy MJ, Brouillet JP, Reilly D, et al. Cathepsin D concentration in breast cancer cytosols: correlation with biochemical, histological and clinical findings. Clin Chem 1991; 37: 101-104.
24- Kandalaft PL, Chang KL, Ahn CW, et al. Prognostic significance of immunohistochemical analysis of cathepsin D in low-stage breast cancer. Cancer 1993; 71: 2756-2763.
25- Razumovic JJ, Stojkovic RR, Petrovecki M, et al. Correlation of two methods for determination of cathepsin D in breast carcinoma (immunohistochemistry and ELISA in cytosol). Breast Cancer Res Treat 1997; 43: 117-122.
26- Zhang Y, Du J, Tian X, et al. Expression of E-cadherin, beta-catenin, cathepsin D, gelatinases and their inhibitors in invasive ductal breast carcinomas. Chin Med J 2007; 120: 1597-1605.
27- Korkolis DP, Tsoli E, Fouskakis D, et al. Tumor histology and stage but not p53, her2-neu or cathepsin-D expression are independent prognostic factors in breast cancer patients. Anticancer Res 2004; 24:2061-2068.
28- Zheng W-Q, Looi L-M, Cheah P-L. A comparison of the pattern of cathepsin D expression in fibroadenoma, fibrocystic diseasae, preinvasive and invasive ductal breast carcinoma. Pathology 1999; 34:247-251.
29- Tetu B, Brisson J, Wang CS, et al. Expression of cathepsin D, stromelysin-3, and urokinase by reactive stromal cells on breast carcinoma prognosis. Cancer 2001; 92: 2957-2964.
30- Tetu B, Brisson J, Cote C, et al. Prognostic significance of cathepsin D expression in node-positive breast carcinoma: an immunohistochemical study. Int J Cancer 1993; 55: 429-435.
31- Gonzales-Vela MC, Garijo MF, Fernandez F, et al. Cathepsin D in host stromal cells is associated with more highly vascular and aggresive breast carcinoma. Histopathology 1999; 34: 35-42.
32- Henry JA, McCarthy AL, Angus B, et al. Prognostic significance of the estrogen-regulated protein, cathepsin D, in breast cancer: an immunohistochemical study. Cancer 1990; 65: 265-271.
33- Raju U, Crissman JD, Zarbo RJ, et al. Epitheliosis of the breast: an immunohistochemical characterization and comparison to malignant intraductal proliferations of the breast. Am J Surg Pathol 1990; 14:939-947.
34- Isola J, Weitz S, Visakorpi T, et al. Cathepsin D expression detected by immunohistochemistry has independent prognostic value in axillary node-negative breast cancer. J Clin Oncol 1993; 11: 36-43.
35- Tavassoli FA, Hoefler H, Rosai J, Holland R, Ellis IO, Schnitt SJ, Boecker W, Heywang-Köbrunner SH, Moinfar F, Lakhani SR: Intraductal proliferative lesions. In Tavassoli FA, Devilee P (Eds.): In World Health Organization Classification of Tumours. Pathology Genetics. Tumours of the Breast and Female Genital Organs. IARC Press: Lyon 2003, pp 63-73.
36- Winstanley JHR, Leinster SJ, Cooke TG, et al. Prognostic significance of cathepsin-D in patients with breast cancer. Br J Cancer 1993;67: 767-772.
37- Castiglioni T, Merino MJ, Elsner B, et al. Immunohistochemical analysis of cathepsins D, B, and L in human breast cancer. Hum Pathol 1994; 25: 857-862.
38- Arner ESJ, Spasokoukotskaja T, Eriksson S. Selective assays for thymidine kinase 1 and 2 and deoxycytidine kinase and their activities in extracts from human cells and tissues. Biochem Biophys Res Commun 1992; 188: 712-718.
39- Wo J, Mao Y, He L, et al. A new cell proliferating marker: Cytosolic thymidine kinase as compared to proliferating cell nuclear antigen in patients with colorectal carcinoma. Anticancer Res 2000; 20: 4815-4820.
40- Zhang F, Shao X, Li H, et al. A monoclonal antibody specific for human thymidine kinase 1. Hybridoma 2001; 20:25-34
41- Fantl V, Richardson MA, Smith R, et al. Gene amplification on chromosome band 11q13 and oestrogen receptor status in breast cancer. Int J Cancer 1990; 26: 423-429.
42- Leong ACK, Hanby AM, Potts HWW, et al. Cell cycle proteins do not predict outcome in grade I infiltrating ductal carcinoma of the breast. Int J Cancer (Pred Oncol) 2000; 89: 26-31.
43- Umekita Y, Ohi Y, Sagara Y, et al. Overexpression of cyclin D1 predicts for poor prognosis in estrogen receptor-negative breast cancer patients. Int J Cancer 2002; 98: 415-418.
44- van Diest PJ, Michalides RJAM, Jannink I, et al. Cyclin D1 expression in invasive breast cancer: correlations and prognostic value. Am J Pathol 1997; 150: 705-711.
45- Moinfar F, Man YG, Lininger RA, et al. Use of keratin 34±E12 as an adjunct in the diagnosis of mammary intraepithelial neoplasia-ductal type-benign and malignant intraductal proliferations. Am J Surg Pathol 1999; 23: 1048-1058.
46- Henry JA, Hennessy C, Levet DL, et al. Int-2 amplification in breast cancer: Association with decreased survival and relationship to amplification of c-erbB2 and c-myc. Int J Cancer 1993; 53: 774-780.
47- Hwang TS, Han HS, Hong YC, et al. Prognostic value of combined analysis of cyclin D1 and estrogen receptor status in breast cancer patients. Pathol Int 2003; 53: 74-80.
48- Arnold A, Papanikolaou A. Cyclin D1 in breast cancer pathogenesis. J Clin Oncol 2005; 23: 4215-4224.
49- Michalides R, Hageman P, van Tinteren H, et al. A clinicopathological study on overexpression of cyclin D1 and of p53 in a series of 248 patients with operable breast cancer. Br J Cancer 1996; 73: 728-734.
50- Nomura AMY, Lee J, Kolonel LN, et al. Breast cancer in two populations with different levels of risk for the disease. Am J Epidemiol 1984; 119: 496-502.
51- Heffelfinger SC, Yassin R, Miller MA, et al. Cyclin D1, retinoblastoma, p53 and Her2/neu protein expression in preinvasive breast pathologies: correlation with vascularity. Pathobiology 2000; 68:129-136.
52- Umekita Y, Yoshida H. Cyclin D1 expression in ductal carcinoma in situ, atypical ductal hyperplasia and usual ductal hyperplasia: an immunohistochemical study. Pathol Int 2000; 50: 527-530.