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Open Access 01-12-2008 | Research

Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma

Authors: Lobna Ayadi, Abdelmajid Khabir, Habib Amouri, Sondes Karray, Abdallah Dammak, Mohamed Guermazi, Tahya Boudawara

Published in: World Journal of Surgical Oncology | Issue 1/2008

Abstract

Background

Breast carcinoma is a disease with a tremendous heterogeneity in its clinical behavior. Newer prognostic factors and predictors of response to therapy are needed. The aim of this study was to evaluate the expression of HER-2, estrogen receptor (ER) and progesterone receptors (PR) in breast carcinoma and to compare it with other prognostic parameters such as histological type and grade, tumor size, patients' age, and lymph node metastases.

Patients and methods

This is a retrospective study conducted in the department of pathology at Sfax University Hospital. Confirmed 155 Cases of breast carcinoma were reviewed in the period between January 2000 and December 2004. We used immunohistochemistry to evaluate the expression of HER-2, ER, and PR receptor and Chi-square and Fisher exact test to correlate immunohistochemical findings with prognostic parameters for breast carcinoma such as patients' age, tumor size, histological type, histological grade and lymph node status.

Results

The mean age of patients was 51.5 years, ranging from 22 to 89 years. 80 (51.6%) of the patients were below 50 years. The percentage of expression of HER-2, ER and PR was 26, 59.4, and 52.3%, respectively. HER-2 was over-expressed (3+) in 18.1% of the cases, was inversely related to ER expression (p = 0.00) and to PR expression (p = 0.048). This over-expression was also associated with a high tumor grade with marginal significance (p = 0.072). A negative correlation was noted between ER and PR expression and SBR grade (p = 0.000) and ER and age (p = 0.002).

Conclusion

HER-2 over-expression was observed in 18.1% of Tunisian breast carcinoma affecting female patients. This group presents apparently an aggressive form of breast carcinoma with high histological grade and negative ER.

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Hsairi M, Fakhfakh R, Ben Abdallah M, Jlidi R, Sellami A, Zheni S, Hmissa S, Achour N, Nacef T: Assessment of cancer incidence in Tunisia 1993–1997. Tunis Med. 2002, 80 (2): 57-64.PubMed

Maalej M, Hentati D, Messai T, Kochbati L, El May A, Mrad K, Romdhane KB, Ben Abdallah M, Zouari B: Breast cancer in Tunisia in 2004: a comparative clinical and epidemiological study. Bull Cancer. 2008, 95: E5-9.PubMed

Maalej M, Frikha H, Ben Salem S, Daoud J, Bouaouina N, Ben Abdallah M, Ben Romdhane K: Breast cancer in Tunisia: clinical and epidemiological study. Bull Cancer. 1999, 86: 302-6.PubMed

Ben Ahmed S, Aloulou S, Bibi M, Landolsi A, Nouira M, Ben Fatma L, Kallel L, Gharbi O, Korbi S, Khaïri H, Kraïem C: Breast cancer prognosis in Tunisian women: analysis of a hospital series of 729 patients. Sante Publique. 2002, 14: 231-41.CrossRefPubMed

Ross JS, Fletcher JA, Linette GP, Stec J, Clark E, Ayers M, Symmans WF, Pusztai L, Bloom KJ: The HER-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist. 2003, 8: 307-25. 10.1634/theoncologist.8-4-307.CrossRefPubMed

Tavassoli FA, Devilee P, Ellis IO, Schnitt SJ, Sastre-Garau X, Jaffe ES, Harris NL, Stein H, World Health Organization Classification of Tumors: Pathology and genetics of tumors of the breast and female genital organs. Fattaneh A. Edited by: Tavassoli, Peter Devilee. 2003, Lyon: IARC Press-WHO, 4:

Allred DC, Harvey JM, Berardo M, Clark GM: Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998, 11: 155-168.PubMed

Kariya S, Ogawa Y, Nishioka A, Moriki T, Ohnishi T, Ito S, Murata Y, Yoshida S: 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): 189-194.PubMed

Pinto AE, Andre S, Pareira T, Nobrega S, Soares J: C-erbB-2 oncoprotein overexpression identifies a subgroup of estrogen receptor positive (ER+) breast cancer patients with poor prognosis. Ann Oncol. 2001, 12: 525-33. 10.1023/A:1011163211802.CrossRefPubMed

10.

Looi LM, Cheah PL: C-erbB-2 oncoprotein amplification in infiltratig ductal carcinoma of breast correlates to high histologic grade and loss of estrogen receptor protein. Malays J Pathol. 1998, 20: 19-23.PubMed

11.

Kaptain S, Tan LK, Chen B: Her-2/neu and breast cancer. Diagn Mol Pathol. 2001, 10: 139-152. 10.1097/00019606-200109000-00001.CrossRefPubMed

12.

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987, 235: 177-82. 10.1126/science.3798106.CrossRefPubMed

13.

Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Metzger D, Chambon P: Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science. 1991, 270: 1491-4. 10.1126/science.270.5241.1491.CrossRef

14.

Pietras RJ, Arboleda J, Reese DM, Wongvipat N, Pegram MD, Ramos L, Gorman CM, Parker MG, Sliwkowski MX, Slamon DJ: HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene. 1995, 10: 2435-46.PubMed

15.

Cormier EM: Decrease in Estradiol-stimulated Progesterone Receptor Production in MCF-7 Cell by epidermal growth factor and possible clinical implication for paracrine-regulated breast cancer growth. Cancer Res. 1989, 49: 576-580.PubMed

16.

Ferlay J, Bray F, Pisani P, Parkin DM: Breast Cancer. Cancer incidence, mortality and prevalence worldwide. Edited by: Lyon: IARC Press. 2004, Ferlay J, Parkin DM, 2:

17.

Abalkhail AA, Zahawi HM, Almasri NM: The role of young population structure in determining age distribution of breast cancer in Jordan. J Bahrain Med Soc. 2003, 15: 28-33.

18.

Almasri NM, Al Hamad M: Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan. Breast Cancer Res. 2005, 7: R598-R604. 10.1186/bcr1200.PubMedCentralCrossRefPubMed

19.

Huang HJ, Neven P, Drijkoningen M, Paridaens R, Wildiers H, Van Limbergen E, Berteloot P, Amant F, Vergote I, Christiaens MMR: Hormone receptors do not predict the HER2/neu status in all age groups of women with an operable breast cancer. Ann Oncol. 2005, 16: 1755-1761. 10.1093/annonc/mdi364.CrossRefPubMed

20.

Seo B K, Pisano ED, Kusimak CM, Koomen M, Pavic D, Lee Y, Cole EB, Lee JY: Correlation of HER-2/neu overexpression with mammography and age distribution in primary breast carcinomas. Acad Radiol. 2006, 13: 1211-18. 10.1016/j.acra.2006.06.015.CrossRefPubMed

21.

Ashba J, Traish AM: Estrogen and progesterone receptor concentrations and prevalence of tumor hormonal phenotypes in older breast cancer patients. Cancer detect Prev. 1999, 23: 238-44. 10.1046/j.1525-1500.1999.99019.x.CrossRefPubMed

22.

Rhodes A, Jasani B, Balaton AJ, Barnes DM, Miller KD: Frequency of estrogen and progesteron receptor positivity by immunohistochemichal analysis in 7016 breast carcinomas: correlation with patient age, assay sensitivity, threshold value, and mammographic screening. J Clin Pathol. 2000, 53: 688-96. 10.1136/jcp.53.9.688.PubMedCentralCrossRefPubMed

23.

Poller DN, Snead DR, Roberts EC, Galea M, Bell JA, Gilmour A, Elston CW, Blamey RW, Ellis IO: Estrogen receptor expression in ductal carcinoma in situ of the breast: relationship to flow cytometric analysis of DNA and expression of the c-erbB-2 oncoprotein. Br J Cancer. 1993, 68: 156-61.PubMedCentralCrossRefPubMed

24.

Holdaway IM, Mountjoy KG: Progesterone and estrogen receptors in human breast cancer. Aust N Z J Med. 1978, 8: 630-8.CrossRefPubMed

25.

Clark GM, Osborne CK, McGuire WL: Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer. J Clin Oncol. 1984, 2: 1102-9.PubMed

26.

Wilking N, Rutqvist LE, Nordenskjold B, Skoog L: Steroid receptor levels in breast cancer. Relationships with age and menopausal status. Acta Oncol. 1989, 28: 807-10. 10.3109/02841868909092312.CrossRefPubMed

27.

Ferno M, Borg A, Johansson U, Norgren A, Olsson H, Ryden S, Sellberg G: Estrogen and progesterone receptor analyses in more than 4,000 human breast cancer samples. A study with special reference to age at diagnosis and stability of analyses: Southern Swedish Breast Cancer Study Group. Acta Oncol. 1990, 29: 129-35. 10.3109/02841869009126532.CrossRefPubMed

28.

Prati R, Apple SK, He J, Gorbein JA, Chan HR: Histopathologic characteristics predicting HER-2/neu amplification in breast cancer. Breast J. 2005, 11 (6): 433-439. 10.1111/j.1075-122X.2005.00125.x.CrossRefPubMed

29.

Ariga R, Zarif A, Korasick J, Reddy V, Siziopikou K, Gattuso P: Correlation of Her 2/neu gene amplification with other prognostic and predictive factors in female breast carcinoma. Breast J. 2005, 11: 278-80. 10.1111/j.1075-122x.2005.21463.x.CrossRefPubMed

30.

Huang HJ, Neven P, Drijkoningen M, Paridaens R, Wildiers H, Van Limbergen E, Berteloot P, Amant F, Vergote I, Christiaens MR: Association between tumor characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer. J Clin Pathol. 2005, 58: 611-616. 10.1136/jcp.2004.022772.PubMedCentralCrossRefPubMed

31.

Bamberger AM, Milde-Langosch K, Schulte HM, Löning T: Progesterone receptor isoforms, PR-B and PR-A, in breast cancer: correlations with clinicopathologic tumor parameters and expression of AP-1 factors. Horm Res. 2000, 54: 32-7. 10.1159/000063434.CrossRefPubMed

32.

Kilinç N, Yaldiz M: P53, c-erbB-2 expression and steroid hormone receptors in breast carcinoma: correlations with histopathological parameters. Eur J Gynaecol Oncol. 2004, 25: 606-10.PubMed

33.

Moriki T, Takahashi T, Hiroi M, Yamane T, Hara H: Histological grade in invasive ductal carcinoma of breast correlates with the proliferative activity evaluated by BrdU: an immunohistochemical study including correlations with p53, c-erbB-2 and estrogen receptor status. Pathol Int. 1996, 46: 417-25.CrossRefPubMed

34.

Kolár Z, Murray PG, Zapletalová J: Expression of c-erbB-2 in node negative breast cancer does not correlate with estrogen receptor status, predictors of hormone responsiveness, or PCNA expression. Neoplasma. 2002, 49: 110-3.PubMed

35.

Boussen H, Bouzaiene H, Ben Hassouna J, Gamoudi A, Benna F, Rahal K: Inflammatory breast cancer in Tunisia: reassessment of incidence and clinicopathological features. Semin Oncol. 2008, 35 (1): 17-24. 10.1053/j.seminoncol.2007.11.017.CrossRefPubMed

36.

Selvarajan S, Wong KY, Khoo KS, Bay BH, Tan PH: Overexpression of c-erbB2 correlates with nuclear morphometry and prognosis in breast carcinoma in Asian women. Pathology. 2006, 38: 528-33. 10.1080/00313020601024060.CrossRefPubMed

37.

Harlozinska A, Bar JK, Wenderski R, Bebenek M: Relationship between c-erbB-2 oncoprotein, epidermal growth factor receptor, and estrogen receptor expression in patients with ductal breast carcinoma. Association with tumor phenotypes. In Vivo. 1996, 10: 217-22.PubMed

38.

Taucher S, Rudas M, Mader RM, Gnant M, Dubsky P, Bachleitner T, Roka S: Do we need HER-2/neu testing for all patients with primary breast carcinoma?. Cancer. 2003, 98: 2547-2553. 10.1002/cncr.11828.CrossRefPubMed

39.

Ali IU, Cmpbell G, Liderau R, Callahan R: Lack of evidence for the prognostic significance of c-erb B-2 amplification in human breast carcinoma. Oncogene Res. 1988, 3: 139-146.PubMed

40.

Andrulis IL, Bull SB, Blackstein ME, Sutherland D, Mak C, Sidlofsky S, Pritzker KP, Hartwick RW, Hanna W, Lickley L, Wilkinson R, Qizilbash A, Ambus U, Lipa M, Weizel H, Katz A, Baida M, Mariz S, Stoik G, Dacamara P, Strongitharm D, Geddie W, McCready D: Neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. J Clin Oncol. 1998, 16 (4): 1340-9.PubMed

41.

Traina A, Agostara B, Marasà L, Calabrò M, Zarcone M, Carruba G: HER2/neu expression in relation to clinicopathologic features of breast cancer patients. Ann N Y Acad Sci. 2006, 1089: 159-67. 10.1196/annals.1386.029.CrossRefPubMed

42.

Ratnatunga N, Lyanapathirana LV: Hormone receptor expression and HER/neu amplification in breast carcinoma in a cohort of Sri Lankans. Ceylon Med J. 2007, 52: 133-6.PubMed

43.

Aziz SA, Pervez S, Khan S, Kayani N, Azam SI, Rahbar MH: Significance of immunohistochemical pattern for prognosis in human breast cancer. Pathol Oncol Res. 2001, 7: 190-6.CrossRefPubMed

44.

Ambazhagan R, Gelber RD, Bettelheim R, Goldhirsch A, Gusterson BA: Association of c-erbB-2 expression and S-phase fraction in the prognosis of node positive breast cancer. Ann Oncol. 1991, 2 (1): 47-53.

45.

Lipton A, Ali SM, Leitzel K, Demers L, Chinchilli V, Engle L, Harvey HA, Brady C, Nalin CM, Dugan M, Carney W, Allard J: Elevated serum Her-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer. J Clin Oncol. 2002, 20 (6): 1467-72. 10.1200/JCO.20.6.1467.CrossRefPubMed

Title: Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma
Authors: Lobna Ayadi
Abdelmajid Khabir
Habib Amouri
Sondes Karray
Abdallah Dammak
Mohamed Guermazi
Tahya Boudawara
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: World Journal of Surgical Oncology / Issue 1/2008
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/1477-7819-6-112

At a glance: The STEP trials

Springer Medicine

Correlation of HER-2 over-expression with clinico-pathological parameters in Tunisian breast carcinoma

Abstract

Background

Patients and methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Patients and methods

Results

Conclusion

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