ORIGINAL ARTICLE
Survivin in breast lesions: immunohistochemical analysis of 196 cases
 
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Submission date: 2016-09-29
 
 
Final revision date: 2017-09-06
 
 
Acceptance date: 2017-10-05
 
 
Publication date: 2018-03-06
 
 
Pol J Pathol 2017;68(4):297-305
 
KEYWORDS
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ABSTRACT
We examined the survivin expression pattern by immunohistochemistry in 43 fibroadenomas and 153 ductal carcinomas of the breast. The subcellular localization of survivin and the intensity of immunoreaction were assessed. We analyzed the differences of survivin expression between fibroadenomas and carcinomas. We also correlated the survivin expression pattern in carcinomas with other clinicomorphological parameters such as the age of patients, the grade and size of primary tumor as well as the lymph node metastasis. Overall, survivin was detected in 107/153 carcinomas (69.9%) and in 26/43 fibroadenomas (60.5%). Statistical analysis confirmed significant correlations between the assessed parameters in fibroadenomas and carcinomas. Grade of carcinomas was significantly related to survivin expression in both subcellular localization and the intensity of immunoreaction. Tumor grade 3 was associated with nuclear positivity and combined nuclear and cytoplasmic localization. Carcinomas larger than 20 mm showed nuclear and combined localization in 81% of cases and higher intensity of survivin immunoreaction was also notably related to larger carcinomas. Statistically significant differences were also observed between subcellular survivin localization and intensity of immunoreaction. Our result suggest that nuclear accumulation of survivin is associated with proliferative fenotype and survivin was shown to be a worse prognostic marker in breast ductal carcinoma.
REFERENCES (56)
1.
Radha RK, Viswanathan P, Krishnaswamy B. Histopathology and Prognostic Indices of Carcinoma Breast with Special Reference to p53 Marker. J Clin Diagn Res 2014; 8: 4-8.
 
2.
Danilewicz M, Stasikowska-Kanicka O, Wągrovska-Danilewicz M. Augmented immunoexpression of survivin correlates with parameters of aggressiveness in prostate cancer. Pol J Pathol 2015; 66: 44-48.
 
3.
Crook NE, Clem RJ, Miller LK. An apoptosis-inhibiting gene with a zinc finger-like motif. J Virol 1993; 67: 2168-2174.
 
4.
Birnahaum MJ, Clem RJ, Miller LK. An apoptosis-inhibiting gene from a nuclear polyhedrosis virus encoding a polypeptide with Cys/His sequence motifs. J Virol 1994; 68: 2521-2528.
 
5.
Reed JC, Doctor KS, Godyik A. The domains of apoptosis: a genomics perspective. Sci STKE 2004; 239: 1-29.
 
6.
Li F, Yang J, Ramnath N, et al. Nuclear or cytoplasmic expression of survivin: What is the significance? Int J Cancer 2005; 114: 509-512.
 
7.
Ryan BM, Konecny GE, Kahlert S, et al. Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1. Ann Oncol 2006; 17: 597-604.
 
8.
Ambrosini G, Adida C, Sirugo G, et al. Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting. J Biol Chem 1998; 273: 11177-11182.
 
9.
Chu JS, Shew JY, Huang CS. Immunohistochemical analysis of survivin expression in primary breast cancers. J Formos Med Assoc 2004; 103: 925-931.
 
10.
Piras F, Murtas D, Minerba L, et al. Nuclear survivin is associated with disease recurrence and poor survival in patients with cutaneous malignant melanoma. Histopathology 2007; 50: 835-842.
 
11.
Tanaka K, Iwamoto S, Gon G, et al. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res 2000; 6: 127-134.
 
12.
O’Driscoll L, Cronin D, Kennedy SM, et al. Lack of prognostic significance of survivin, survivin-DEx3, survivin-2B, galectin-3, bag-1, bax-a and MRP-1 mRNAs in breast cancer. Cancer Lett 2003; 201: 225-236.
 
13.
Kennedy SM, O’Driscoll L, Purcell R, et al. Prognostic importance of survivin in breast cancer. Br J Cancer 2003; 88: 1077-1083.
 
14.
Span PN, Sweep FC, Wiegerinck ET, et al. Survivin is an independent prognostic marker for risk stratification of breast cancer patients. Clin Chem 2004; 50: 1986-1993.
 
15.
Hinnis AR, Luckett JC, Walker RA. Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients. Br J Cancer 2007; 96: 639-645.
 
16.
Taubert H, Heidenreich CH, Holzhausen HJ, et al. Expression of survivin detected by immunohistochemistry in the cytoplasm and in the nucleus is associated with prognosis of leiomyosarcoma and synovial sarcoma patients. BMC Cancer 2010; 10: 65.
 
17.
Faversani A, Vaira V, Moro GP, et al. Survivin family proteins as novel molecular determinants of doxorubicin resistance in organotypic human breast tumors. Breast Cancer Res 2014; 16: R55.
 
18.
Al-Joudi FS, Iskandar ZA, Hasnan J, et al. Expression of survivin and its clinicopathological correlationsin invasive ductal carcinoma of the breast. Singapore Med J 2007; 48: 607-614.
 
19.
Adamkov M, Halasova E, Kajo K, et al. Survivin: a promising biomarker in breast carcinoma. Neoplasma 2010; 57: 572-577.
 
20.
Ranade KJ, Nerurkar AV, Phulpagar MD, et al. Expression of survivin and p53 proteins and their correlation with hormone receptor status in Indian breast cancer patients. Indian J Med Sci 2009; 63: 481-490.
 
21.
Ryan B, O´Donovan N, Browne B, et al. Expression of survivin and its splice variants survivin-2B and survivin-Ex3 in breast cancer. Br J Cancer 2005; 17: 120-124.
 
22.
Yang D, Welm A, Bishop JM. Cell survival in the absence of survivin. Proc Natl Acad Sci 2004; 101: 15100-15105.
 
23.
Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998; 396: 580-584.
 
24.
Nassar A, Lawson D, Cotsonis G, et al. Survivin and caspase-3 expression in breast cancer: correlation with prognosis parameters, proliferation, angiogenesis, and outcome. Appl Immunohistochem Mol Morphol 2008b; 16: 113-120.
 
25.
Altieri DC. The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med 2001; 7: 542-547.
 
26.
Altieri DC. Validating survivin as a cancer therapeutic target. Nat Rev Cancer 2003; 3: 46-54.
 
27.
Lacasse E, Baird S, Korneluk RG, et al. The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 1998; 17: 3247-3259.
 
28.
Fenhzhi L. Survivin study: What is the next wave? J Cell Physiol 2003; 197: 8-29.
 
29.
Duffy MJ, O’Donovan N, Brennan DJ, et al. M. Survivin: a promising tumor biomarker. Cancer Lett 2007; 249: 49-60.
 
30.
Zhang SQ, Qiang SY, Yang WB, et al. Expression of survivin in different stages of carcinogenesis and progression of breast cancer. Ai Zheng 2004; 23: 697-700.
 
31.
Brennan DJ, Rexhepaj E, O‘Brien SL, et al. Altered cytoplasmic-to-nuclear ratio of survivin is a prognostic indicator in breast cancer. Clin Cancer Res 2008; 14: 2681-2689.
 
32.
Oh JW, Yang WI, Lee MJ, et al. The prognostic significance of survivin expression in breast cancer. J Breast Cancer 2009; 12: 285-294.
 
33.
Adamkov M, Lauko L, Rajcani J, et al. Expression of antiapoptotic protein survivin in malignant melanoma. Biologia 2009a; 64: 840-844.
 
34.
Adamkov M, Lauko L, Balentova S, et al. Expression pattern of anti-apoptotic protein survivin in dysplastic nevi. Neoplasma 2009b; 56: 130-135.
 
35.
Barnes N, Haywood P, Flint P, et al. Survivin expression in in situ and invasive breast cancer relates to COX-2 expression and DCIS recurrence. Br J Cancer 2006; 94: 253-258.
 
36.
Jin Q, Feng L, Behrens, C, et al. Implication of AMP-Activated Protein Kinase and Akt-Regulated Survivin in Lung Cancer Chemopreventive Activities of Deguelin. Cancer Res 2007; 67: 11630-11639.
 
37.
Rexhepaj E, Jirstrom K, O´Connor, DP, et al. Validation of cytoplasmic-to-nuclear ratio of survivin as an indicator of improved prognosis in breast cancer. BMC Cancer 2010; 10: 639.
 
38.
Knauer SK, Bier C, Habtemichael N, et al. The survivin-Crm1 interaction is essential for chromosomal passenger complex localization and function. EMBO Rep 2006; 7: 1259-1265.
 
39.
Knauer SK, Krämer OH, Knösel T, et al. Nuclear export is essential for the tumor-promoting activity of survivin. FASEB J 2007; 21: 207-216.
 
40.
Suga K, Yamamoto, T, Yamada Y, et al. Correlation between transcriptional expression of survivin isoforms and clinicopathological findings in human colorectal carcinomas. Oncol Rep 2005; 13: 891-897.
 
41.
Duffy MJ. Clinical uses of tumor markers: a critical review. Crit Rev Clin Lab Sci 2001; 38: 225-262.
 
42.
Song J, Su H, Zhou Y, Guo L. Prognostic value of survivin expression in breast cancer patients: a meta-analysis. Tumor Biology 2013; 34: 2053-2062.
 
43.
Li Y, Ma X, Wu X, et al. Prognostic significance of survivin in breast cancer: meta-analysis. Breast J 2014; 20: 514-524.
 
44.
Chen H-I, Zhou M-q, Tian W, et al. Effect of age on breast cancer patient prognoses: a population-based study using the SEER 18 database. PLoS ONE 2016; 11(10): e0165409. https://doi.org/10.1371/journa....
 
45.
Rakha EA, Reis-Filho JS, Baehner F, et al. Breast cancer prognostic classification in the molecular era: the role of histological grade. Breast Cancer Res 2010; 12: 207.
 
46.
Frkovic-Grazio S, Bracko M. Long term prognostic value of Nottingham histological grade and its components in early (pT1N0M0) breast carcinoma. J Clin Pathol 2002; 55: 88-92.
 
47.
Schwartz AM, Henson DE, Chen D, Rajamarthandan S. Histologic grade remains a prognostic factor for breast cancer regardless of the number of positive lymph nodes and tumor size. Arch Pathol Lab Med 2014; 138: 1048-1052.
 
48.
Michaelson JS, Silverstein M, Wyatt J, et al. Predicting the survival of patients with breast carcinoma using tumor size. Cancer 2002; 95: 713-723.
 
49.
Foulkes WD. Size surprise? Tumour size, nodal status, and outcome after breast cancer. Current Oncology 2012; 19: 241-243.
 
50.
Largillier R, Ferrero JM, Doyen J, et al. Prognostic factors in 1038 women with metastatic breast cancer. Ann Oncol 2008; 19: 2012-2019.
 
51.
Arpino G, Milano M, De Placido S. Features of aggressive breast cancer. The Breast 2015; 24: 594-600.
 
52.
Carter ChL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24, 740 breast cancer cases. Cancer 1989; 63: 181-187.
 
53.
ElSheikh SM, Omar TA, Abdel Halim HS, AbdelSattar MF. Expression of the antiapoptotic survivin in the adenomatoid odontogenic tumors. Tanta Dental Journal 2014; 11: 174-179.
 
54.
Kim S-A, Hong R. Significance of intracellular localization of survivin in cervical squamous cell lesions: Correlation with disease progression. Oncol Lett 2014; 7: 1589-1593.
 
55.
Adamkov M, Výbohová D, Horáček J, et al. Survivin expression in breast lobular carcinoma: correlations with normal breast tissue and clinicomorphological parameters. Acta Histochem 2013; 115: 412-417.
 
56.
Adamkov M, Kajo K, Vybohova D, et al. Correlations of survivin expression with clinicomorphological parameters and hormonal receptor status in breast ductal carcinoma. Neoplasma 2012; 59: 30-37.
 
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