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Significance of Bcl-2 and Bax proteins in cervical carcinogenesis: an immunohistochemical study in squamous cell carcinoma and squamous intraepithelial lesions

Cheah, Phaik Leng , and Looi, Lai Ming, (2006) Significance of Bcl-2 and Bax proteins in cervical carcinogenesis: an immunohistochemical study in squamous cell carcinoma and squamous intraepithelial lesions. Malaysian Journal of Pathology, 28 (1). pp. 1-5. ISSN 0126-8635

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Official URL: http://www.mjpath.org.my

Affiliations

University of Malaya. Faculty of Medicine. Dept. of Pathology

Abstract

Sixteen low grade (LSIL), 22 high grade (HSIL) squamous intraepithelial lesions, 28 invasive (13 stage I and 15 stage II-IV) squamous cell carcinoma (SCC) and 15 benign cervices were immunohistochemically studied for involvement of Bcl-2 and Bax proteins in cervical carcinogenesis. 4-μm sections of the cases were immunostained for Bcl-2 (Clone 124: Dako) and Bax (Dako) and staining intensity was rated as 1 (light), 2 (moderate) and 3 (strong) and percentage cellular staining as 0 (negative), 1 (1-25%), 2 (26-50%), 3 (51-75%) and 4 (>75%) with score derived by multiplying staining intensity and percentage positivity. The cut-off value, indicating upregulated expression, was computed as >2 for Bcl-2 and >8 for Bax. Bcl-2 was upregulated (p<0.05) in HSIL and Bax in SCC when compared with benign cervical squamous epithelium. Bcl-2 expression was confined to the lower third of the epithelium in the benign cervices and LSIL. In HSIL, expression reached the middle and upper thirds. 4 (30.8%) HSIL with upregulated Bcl-2 demonstrated intensification of staining around the basement membrane. SCCs showed “diffuse” (evenly distributed) or “basal” (intensified staining around the periphery of the invading tumour nests) expression of Bcl-2. Of the 5 SCCs with upregulated Bcl-2, 1 of 2 (50%) stage I and 3 (100%) stage II-IV tumours exhibited the “basal” pattern. Benign cervical squamous epithelium, LSIL, HSIL and SCC showed a generally diffuse Bax expression. Thus, Bcl-2 and Bax appeared to be upregulated at different stages of cervical carcinogenesis, Bcl-2 in HSIL and Bax after invasion. Intensification of staining of Bcl-2 at the basement membrane in some HSIL and SCC is interesting and may augur for increased aggressiveness.

Item Type:Journal
Keywords:cervical carcinoma, Bcl-2, Bax, immunohistochemistry
Subjects:R Medicine
ID Code:1770

Warner TF. Apoptosis. Lancet 1972;2:1252.

Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972;26:239-57.

Monaghan P, Robertson D, Amos TAS, Dyer MJS, Mason DY, Greaves MF. Ultrastructural localization of bcl-2 protein. J Histochem Cytochem 1992;40:1819-25.

Krajewski S, Tanaka S, Takayama S, Schibler MJ,distribution of the bcl-2 oncoprotein: residence in the nuclear envelope, endoplasmic reticulum and outer mitochondrial membranes. Cancer Res 1993;53:4701-14.

De Jong D, Prins FA, Mason DY, Reed JC, Van Ommen GB, Kluin PM. Subcellular localization of the bcl-2 protein in malignant and normal lymphoid cells. Cancer Res 1994;54:259-60.

Chen-Levy Z, Cleary ML. Membrane topology of the bcl-2 proto-oncogene protein demonstrated in vitro. J Biol Chem 1990;265:4929-33.

Akao Y, Otsuki Y, Kataoka S, Ito Y, Tsujimoto Y. Multiple subcellular localization of bcl-2: detection in nuclear outer membrane, endoplasmic reticulum membrane and mitochondrial membrane. Cancer Res 1994;54:2468-71.

Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993;74:609-19.

Chao DT, Korsmeyer SJ. BCL-2 family: regulators of cell death. Annu Rev Immunol 1998;1;16:395-419.

Reed JC. Bcl-2 family proteins. Oncogene 1998;1;17:3225-36.

Zamzami N, Brenner C, Marzo I, Susin S, Kroemer G. Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins. Oncogene 1998;1;16:2265-82.

Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;1;18) chromosome translocation. Science 1984;226:1097-99.

Tsujimoto Y, Cossman J, Jaffe E, Croce CM. Involvement of the bcl-2 gene in human follicular lymphoma. Science 1985;228:1440-3.

Tsujimoto Y, Croce CM. Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma. Proc Natl Acad Sci USA 1986;83:5214-8.

Krajewska M, Fenoglio-Preiser CM, Krajewski S, et al. Immunohistochemical analysis of Bcl-2 family proteins in adenocarcinomas of the stomach. Am J Pathol 1996;1;149:1449-57.

Krajewska M, Krajewski S, Epstein JI, et al. Immunohistochemical analysis of bcl-2, bax, bcl-x and mcl-1 expression in prostate cancers. Am J Pathol 1996;1;148:1567-76.

Veronese S, Mauri FA, Caffo O, et al. Bax immunohistochemical expression in breast carcinoma: a study with long term follow-up. Int J Cancer 1998;79:13-8.

Saegusa M, Takano Y, Hashimura M, Shoji Y, Okayasu I. The possible role of bcl-2 expression in the progression of tumors of the uterine cervix. Cancer 1995;76:2297-303.

Dimitrakakis C, Kymionis G, Diakomanolis E, et al. The possible role of p53 and bcl-2 expression in cervical carcinomas and their premalignant lesions. Gynecol Oncol 2000;77:129-36.

Tjalma W, De Cuyper E, Weyler J, et al. Expression of bcl-2 in invasive and in situ carcinoma of theuterine cervix. Am J Obstet Gynecol 1998;178:113-7.

ter Harmsel B, Kuijpers J, Smedts F, Jeunink M, Trimbos B, Ramaekers F. Progressing imbalance between proliferation and apoptosis with increasing severity of cervical intraepithelial neoplasia. Int J Gynecol Pathol 1997;1;16:205-1111.

Dellas A, Schultheiss E, Holzgreve W, Oberholzer M, Torhorst J, Gudat F. Investigation of the Bcl-2 and C-myc expression in relationship to the Ki-67 labelling index in cervical intraepithelial neoplasia. Int J Gynecol Pathol 1997;1;16:212-8.

Nakamura T, Nomura S, Sakai T, Nariya S. Expression of bcl-2 oncoprotein in gastrointestinal and uterine carcinomas and their premalignant lesions. Hum Pathol 1997;28:309-15.

Tjalma W, Weyler J, Goovaerts G, De Pooter C, Van Marck E, van Dam P. Prognostic value of bcl-2 expression in patients with operable carcinoma of the uterine cervix. J Clin Pathol 1997;50:33-6.

Ter Harmsel B, Smedts F, Kuupers J, Jeunink M, Trimbos B, Ramaekers F. Bcl-2 immunoreactivity increases with severity of CIN: a study of normal cervical epithelia, CIN, and cervical carcinoma. J Pathol 1996;1;179:26-30.

Ohno T, Nakano T, Niibe Y, Tsujii H, Oka K. Bax protein expression correlates with radiation-induced apoptosis in radiation therapy for cervical carcinoma. Cancer 1998;83:103-10.

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