Evaluation of Her- 2 neu over expression in morphological variants of cervical carcinomas using immunohistoichemistry: A study of 25 cases.
Keywords:
Her- 2 neu, cervical carcinomas, immunohistoichemistry
Abstract
Introduction: Carcinoma of uterine cervix is the second most prevalent cancer among women worldwide and remains a major gynecological malignancy in developing countries. HER-2/neu,a pro-oncogene is a cell membrane surface bound tyrosine kinase receptor and is involved in signal transduction pathway leading to cell growth and differentiation.Aim: The present study is conducted to evaluate the over-expression of HER-2/neu in carcinoma cervix, its pattern of membranous staining and correlation with histological type, grade of tumor and stage of disease wherever available.Methods: A part retrospective and part prospective study was done on a total of 25 cervical biopsies and hysterectomies specimen. Tissue blocks with extensive necrosis or hemorrhage were excluded from the study and immunohistochemistry for HER-2/neu was done. The percentage of cells showing the membranous positivity for HER2/neu, extent of its positivity in the cervical epithelium in different lesions of the cervix and membranous intensity of HER2/neu positive cells was noted. The HER2/neu expression was then correlated with morphological diagnosis, grade of lesion, invasion and lymph node metastasis in hysterectomies.Results: 18 cases were reported to be SCC (72%) , while Adenocarcinoma (12%) and Adenosquamous (16%) carcinoma constituted small subgroups of 3 and 4 cases, respectively, 13(52%) cases of carcinoma cervix were found to be positive for HER 2/neu while 12/25 cases(48%) were negative. 11 cases of SCC were positive for HER2/neu, 2/4 adenosquamous carcinoma cases were positive. No adenocarcinoma cases were found to be positive for HER2/neu. 12 carcinoma cervix cases show <10% cells staining for HER2 /neu (48%). 9 cases involved 10-20% of cells (36%), while only four cases had positive cell count > 20% (6%). Of the 19 of carcinoma cervix with known staging, (9) were of stage 1, 1/9 cases of stage I showed HER2/neu positivity (2+), 4/6 of stage II were moderately positive (2+) for the marker 2/ 2 of stage IV cases showed 2+ and 3+ positivity.The present study showed SCC to be the most common carcinoma with 52% of carcinoma cervix cases expressed positivity for HER-2/neu. Maximum number of carcinoma cases showed 2+ HER-2/neu intensity. HER-2/neu positivity was found to be highest in SCC, followed by adenosquamous and adenocarcinoma. Her 2/neu was found to be over expressed in higher stage with high percentage positivity.Conclusion: The high incidence of HER-2/neu amplification in cervical cancer suggests the role of this gene in tumorigenesis and this study emphasize HER-2/neu overexpression in cervical carcinoma.References
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26. Wong, A. J., Ruppert, J. M., Eggleston, J., Hamilton, S. R., Baylin, S. B., and Vogelstein, B. Gene amplification of C-myc and N-myc in small cell carcinoma of the lung. Science (Washington DC), 233: 461—464, 1986.”8201,991.
27. Brumm C, Riviere A, Wilckens C: Immunohistochemical investigation and northern blot analysis of c-erb B2 expression in normal,premalignant and malignant tissue of cervix uteri.Virchow archeive pathol Anat. 417:477-484,1990.
28. Kihana T, Tsuda H,Teshima S, Nomoto K, Tsugane S, Sonada T et al.Prognostic Significance of over expression of c-erbB-2 Protein in Adenocarcinoma of Uterine Cervix. Cancer. 1994; 73(1): 148-153.
2. Rotkin, I. D. Relation of adolescent coitus to cervical cancer risk. Journal of the American Medical Association;1962;179,486.
3. Fauci S, Braunwald E , Kasper D, Hauser SL, Lengo D, Jameson JL et al. Gynecologic Malignancy in Harrison’s Principles of Internal Medicine. Seventeenth Ed.USA: Mc Graw-Hill; 2008;604-609.
4. Kumar V, Abbas AK, Fausto N, Astor JC,. Female Genital Tract in Robbins and Cotran Pathologic Basis of Disease. Eighth Ed. Philadelphia: Elsevier; 2010;1020-1025.
5. Hung MC, Matin A, Zhang Y, Xing X, Sorgi F, Huang L, et al. HER-2/neu-targeting gene therapy-a review. Gene 1995;159:65-71.
6. Duenas-Gonzalez A, Cetina l, Mariscal I, Garza J. Cancer Treat Rev. 2003;29(5):389-99.
7. Ray A, Naik SL, Sharma BK. Distribution of prognostically unfavourable product of C-erb B-2 oncogene and EGFR in carcinomas of breast and the uterine cervix. Indian J Physiol Pharmacol 2002;46:423-33.
8. Popescu, N. C., King, C. R., and Kraus, M. H. Localization of the human erbB2 gene on normal and rearranged chromosomes 17 to bands q12.2l.32. Genomics, 4:362- 366,1989.
9. Bargmann CL, Hung MC, Weinberg RA. The new oncogene encodes an epidermal growth factor receptor-related protein. Nature;1986;4:362-6.
10. Nevin J, Liang D, Kaye P, McCulloch T. The Significance of ErbB-2 Immunostaining in Cervical Cancer. Gyenecologic Oncology. 1999;73:354-358.
11. Mitra A B,Murty VVVS, Pratap M, Sodhani P, Chaganti R S K.ErbB-2 (HER2/neu) Oncogene is frequently amplified in Squamous Cell Carcinoma of the Uterine Cervix. Cancer Research. 1994; 54: 637-639.
12. Nakano T, Oka K, Morita S. Correlation of cervical carcinoma c-erbB2 oncogene with cell proliferation parameters in patients treated with radiation therapy for cervical carcinoma. Cancer 1997;79:513-20.
13. Gupta N, Singh S, Marwah N, Kumar S, Chabra S, Sen R.HER-2/neu Expression in Lesion of Uterine Cervix; Is It Reliable and Consistent? Indian J Pathol Micro. 2009; 52(4):482-485.
14. Marwah N, Garg M, Singh S, Sethi D, Sen R. Unusual form of squamous cell carcinoma of the cervix extending in situ into the endometrium: Three case reports and review of literature. Int J App Basic Med Res 2012;2:139-41
15. Ray A, Naik S. L. D. and Sharma B. K. Distribution of prognostically unfavourable product of c-erbB-2 oncogene and EGF-R in carcinomas of the breast and uterine cervix. Indian J Physiol Pharmacol 2002; 46(4):423-33.
16. Graham J.B. Characteristics of women with various gynaecological cancers.Obstetrics and Gynecology, 1964;23,176.
17. Horton J: Trastuzumab use in breast cancer: clinical issues. Cancer Control 2002, 9:499-507.
18. Bethwaite P, Yeong M 1, Holloway 1 et al1992. The prognosis of adenosquamous carcinoma of the uterine cervix. Br J Obstet Gynaecol99: 745-750.
19. Goud KI, Dayakar S, Vijyalaxmi K, Babu SJ, Vijay ARP. Evaluatiion of HER-2/neu status in breast cancer specimens using immunohistochemistry (IHC) & fluorescence in-situ hybridization (FISH) assay. The Indian Journal of Medical Research.2012;135(3):312-7.
20. Rosty C, Couturier J, Genin P. et al. Overexpression/amplification of HER-2/neu is uncommon in invasive carcinoma of uterine cervix. Int J Gynecol Pathol. 2004;23(1):13-17.
21. Hale R J,Buckley C H,Fox H,Williams J.Prognostic value of c-erbB-2 in expression of Uterine Cervical Carcinoma. J Clin Pathol. 1992; 45: 594-596.
22. Califano D, Losito S, Pisano C. et al. Significance of erbB-2 immunoreactivity in cervical cancer.Front Biosci, 2006 sep 1;11:2071-6.
23. Nadubisi B, Sanz S et al. The prognostic value of HER-2/neu oncogene in cervical cancer.Ann Clin Lab Sci. 1997;27:396-401.
24. Alma Chavez-Blanco, Victor Perez-Sanchez et al. HER-2/neu expression in cervical cancer as a potential therapeutic target. BMC cancer 2004;4:59.
25. Kersemaeckers AF, Fleuren G J, Kenter G G, Broek LV, Uljee SM, Hermans J et al.Oncogene overexpression of Epidermal Growth Factor Receptor is associated with poor prognosis.Clinical Cancer Research. 1999; 5: 577-586.
26. Wong, A. J., Ruppert, J. M., Eggleston, J., Hamilton, S. R., Baylin, S. B., and Vogelstein, B. Gene amplification of C-myc and N-myc in small cell carcinoma of the lung. Science (Washington DC), 233: 461—464, 1986.”8201,991.
27. Brumm C, Riviere A, Wilckens C: Immunohistochemical investigation and northern blot analysis of c-erb B2 expression in normal,premalignant and malignant tissue of cervix uteri.Virchow archeive pathol Anat. 417:477-484,1990.
28. Kihana T, Tsuda H,Teshima S, Nomoto K, Tsugane S, Sonada T et al.Prognostic Significance of over expression of c-erbB-2 Protein in Adenocarcinoma of Uterine Cervix. Cancer. 1994; 73(1): 148-153.
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2016-06-27
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