p53 and bcl2 expression in malignant and premalignant lesions of uterine cervix and their correlation with human papilloma virus 16 and 18

Shailaja Shukla; Jasmita Dass; Mukta Pujani

doi:10.4103/2278-330X.126524

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FEMALE REPRODUCTIVE TRACT TUMORS : Original Article

03 (

); 048-053

doi:

10.4103/2278-330X.126524

p53 and bcl2 expression in malignant and premalignant lesions of uterine cervix and their correlation with human papilloma virus 16 and 18

Shailaja Shukla¹, Jasmita Dass¹, Mukta Pujani^1,

1 Department of Pathology, Lady Hardinge Medical College and Smt. Sucheta Kriplani Hospital, New Delhi

2 Department of Pathology, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi

*Corresponding author: Dr. Mukta Pujani. drmuktapujani@gmail.com

Published: 2020-12-31

MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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Abstract

Background and Objective: Persistent high risk human papilloma virus (HPV) infection is probably the best predictor of increased risk of cervical cancer, but expression of certain markers of cell proliferation and apoptosis have been studied. The present study was conducted to evaluate the expression of p53 and bcl2 in premalignant and malignant lesions of cervix and its correlation with HPV type 16 and 18. Materials and Methods: The study comprised of 35 cases (including 24 prospective cases and 11 retrospective cases) of premalignant and malignant lesions of the cervix. Slides were stained with Hematoxylin and Eosin and p53, bcl2 (immunohistochemistry), HPV 16 and HPV 18 (in situ hybridization). Results: p53 positivity was seen in 8/19 (42.1%) cases of cervical intraepithelial neoplasia (CIN) and 8/16 (50%) cases of carcinoma cervix, the difference not significant statistically. The difference in bcl2 expression in CIN versus carcinoma cervix (84.21% vs. 43.75%) was statistically significant (P = 0.030). There was no significant difference between p53 and bcl2 expression and the stage and grade of the tumors. Seven out of 19 cases of CIN (36.84%) were positive for HPV 16/18 infection and 8/16 cases (50%) of carcinoma cervix were HPV positive (P = 0.628). Conclusions : No significant association was found between HPV 16/18 infection and p53 and bcl2 expression in premalignant and malignant lesions of uterine cervix. Although, bcl2 staining showed a significant difference between CIN and carcinoma cervix, a larger case series is required to assess the association between HPV infection and overexpression of p53 and bcl2 proteins in these lesions.

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References

Park K. Park′s textbook of Preventive and Social Medicine. 17 th ed. Jabalpur, M.P., India: M/s Banarsidas Bhanot; 2002. p. 285-7.
Longatto Filho A, Utagawa ML, Shirata NK, Pereira SM, Namiyama GM, Kanamura CT, et al. Immunocytochemical expression of p16INK4A and Ki-67 in cytologically negative and equivocal pap smears positive for oncogenic human papillomavirus. Int J Gynecol Pathol 2005;24:118-24.
Kurvinen K, Syrjänen K, Syrjänen S. p53 and bcl-2 proteins as prognostic markers in human papillomavirus-associated cervical lesions. J Clin Oncol 1996;14:2120-30.
al-Saleh W, Delvenne P, Greimers R, Fridman V, Doyen J, Boniver J. Assessment of Ki-67 antigen immunostaining in squamous intraepithelial lesions of the uterine cervix. Correlation with the histologic grade and human papillomavirus type. Am J Clin Pathol 1995;104:154-60.
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.
Thomas M, Pin D, Banks L. The role of E6 and p53 interaction in molecular pathogenesis of HPV. Oncogene 1999;18:7690-770.
Grace VM, Shalini JV, lekha TT, Devaraj SN, Devaraj H. Co-overexpression of p53 and bcl-2 proteins in HPV-induced squamous cell carcinoma of the uterine cervix. Gynecol Oncol 2003;91:51-8.
Dimitrakakis C, Kymionis G, Diakomanolis E, Papaspyrou I, Rodolakis A, Arzimanoglou I, et al. The possible role of p53 and bcl-2 expression in cervical carcinomas and their premalignant lesions. Gynecol Oncol 2000;77:129-36.
Jeffers MD, Richmond J, Farquharson M, McNicol AM. p53 immunoreactivity in cervical intraepithelial neoplasia and non-neoplastic cervical squamous epithelium. J Clin Pathol 1994;47:1073-6.
Dellas A, Schultheiss E, Almendral AC, Gudat F, Oberholzer M, Feichter G, et al. Altered expression of mdm-2 and its association with p53 protein status, tumor-cell-proliferation rate and prognosis in cervical neoplasia. Int J Cancer 1997;74:421-5.
Cheah PL, Looi LM. p53 immunohistochemical expression: Messages in cervical carcinogenesis. Pathology 2002;34:326-31.
Rajaram S, Gupta G, Agarwal S, Goel N, Singh KC. High-risk human papillomavirus, tumor suppressor protein p53 and mitomycin-C in invasive squamous cell carcinoma cervix. Indian J Cancer 2006;43:156-62.
Skomedal H, Kristensen GB, Lie AK, Holm R. Aberrant expression of the cell cycle associated proteins TP53, MDM2, p21, p27, cdk4, cyclin D1, RB, and EGFR in cervical carcinomas. Gynecol Oncol 1999;73:223-8.
Jain D, Srinivasan R, Patel FD, Kumari Gupta S. Evaluation of p53 and Bcl-2 expression as prognostic markers in invasive cervical carcinoma stage IIb/III patients treated by radiotherapy. Gynecol Oncol 2003;88:22-8.
Chen HY, Hsu CT, Lin WC, Tsai HD, Chang WC. Prognostic value of p53 expression in stage IB1 cervical carcinoma. Gynecol Obstet Invest 2000;49:266-71.
Avall-Lundqvist EH, Silfverswärd C, Aspenblad U, Nilsson BR, Auer GU. The impact of tumour angiogenesis, p53 overexpression and proliferative activity (MIB-1) on survival in squamous cervical carcinoma. Eur J Cancer 1997;33:1799-804.
Rajkumar T, Rajan S, Baruah RK, Majhi U, Selvaluxmi G, Vasanthan A. Prognostic significance of Bcl-2 and p53 protein expression in stage IIB and IIIB squamous cell carcinoma of the cervix. Eur J Gynaecol Oncol 1998;19:556-60.
Giarnieri E, Mancini R, Pisani T, Alderisio M, Vecchione A. Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax expression in invasive and in situ squamous cell carcinoma of the uterine cervix. Clin Cancer Res 2000;6:3600-6.
Wootipoom V, Lekhyananda N, Phungrassami T, Boonyaphiphat P, Thongsuksai P. Prognostic significance of Bax, Bcl-2, and p53 expressions in cervical squamous cell carcinoma treated by radiotherapy. Gynecol Oncol 2004;94:636-42.
Helland A, Holm R, Kristensen G, Kaern J, Karlsen F, Trope C, et al. Genetic alterations of the TP53 gene, p53 protein expression and HPV infection in primary cervical carcinomas. J Pathol 1993;171:105-14.
Munakata S, Watanabe O, Ohashi K, Morino H. Expression of Fas ligand and bcl-2 in cervical carcinoma and their prognostic significance. Am J Clin Pathol 2005;123:879-85.
Tjalma W, De Cuyper E, Weyler J, Van Marck E, De Pooter C, Albertyn G, et al. Expression of bcl-2 in invasive and in situ carcinoma of the uterine cervix. Am J Obstet Gynecol 1998;178:113-7.
Aletra C, Ravazoula P, Scopa C, Kounelis S, Sotiropoulou G, Kourounis G, et al. Expression of bcl-2 and bax in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Eur J Gynaecol Oncol 2000;21:494-8.
Crawford RA, Caldwell C, Iles RK, Lowe D, Shepherd JH, Chard T. Prognostic significance of the bcl-2 apoptotic family of proteins in primary and recurrent cervical cancer. Br J Cancer 1998;78:210-4.
Choudhury M, Singh S. Detection of HPV16 and 18 by in situ hybridization in precancerous and cancerous lesions of cervix. Indian J Pathol Microbiol 2006;49:345-7.
Menon MM, Simha MR, Doctor VM. Detection of human papillomavirus (HPV) types in precancerous and cancerous lesions of cervix in Indian women: A preliminary report. Indian J Cancer 1995;32:154-9.

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[1] Park K. Park′s textbook of Preventive and Social Medicine. 17 th ed. Jabalpur, M.P., India: M/s Banarsidas Bhanot; 2002. p. 285-7.

[2] Longatto Filho A, Utagawa ML, Shirata NK, Pereira SM, Namiyama GM, Kanamura CT, et al. Immunocytochemical expression of p16INK4A and Ki-67 in cytologically negative and equivocal pap smears positive for oncogenic human papillomavirus. Int J Gynecol Pathol 2005;24:118-24.

[3] Kurvinen K, Syrjänen K, Syrjänen S. p53 and bcl-2 proteins as prognostic markers in human papillomavirus-associated cervical lesions. J Clin Oncol 1996;14:2120-30.

[4] al-Saleh W, Delvenne P, Greimers R, Fridman V, Doyen J, Boniver J. Assessment of Ki-67 antigen immunostaining in squamous intraepithelial lesions of the uterine cervix. Correlation with the histologic grade and human papillomavirus type. Am J Clin Pathol 1995;104:154-60.

[5] 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.

[6] Thomas M, Pin D, Banks L. The role of E6 and p53 interaction in molecular pathogenesis of HPV. Oncogene 1999;18:7690-770.

[7] Grace VM, Shalini JV, lekha TT, Devaraj SN, Devaraj H. Co-overexpression of p53 and bcl-2 proteins in HPV-induced squamous cell carcinoma of the uterine cervix. Gynecol Oncol 2003;91:51-8.

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

[9] Jeffers MD, Richmond J, Farquharson M, McNicol AM. p53 immunoreactivity in cervical intraepithelial neoplasia and non-neoplastic cervical squamous epithelium. J Clin Pathol 1994;47:1073-6.

[10] Dellas A, Schultheiss E, Almendral AC, Gudat F, Oberholzer M, Feichter G, et al. Altered expression of mdm-2 and its association with p53 protein status, tumor-cell-proliferation rate and prognosis in cervical neoplasia. Int J Cancer 1997;74:421-5.

[11] Cheah PL, Looi LM. p53 immunohistochemical expression: Messages in cervical carcinogenesis. Pathology 2002;34:326-31.

[12] Rajaram S, Gupta G, Agarwal S, Goel N, Singh KC. High-risk human papillomavirus, tumor suppressor protein p53 and mitomycin-C in invasive squamous cell carcinoma cervix. Indian J Cancer 2006;43:156-62.

[13] Skomedal H, Kristensen GB, Lie AK, Holm R. Aberrant expression of the cell cycle associated proteins TP53, MDM2, p21, p27, cdk4, cyclin D1, RB, and EGFR in cervical carcinomas. Gynecol Oncol 1999;73:223-8.

[14] Jain D, Srinivasan R, Patel FD, Kumari Gupta S. Evaluation of p53 and Bcl-2 expression as prognostic markers in invasive cervical carcinoma stage IIb/III patients treated by radiotherapy. Gynecol Oncol 2003;88:22-8.

[15] Chen HY, Hsu CT, Lin WC, Tsai HD, Chang WC. Prognostic value of p53 expression in stage IB1 cervical carcinoma. Gynecol Obstet Invest 2000;49:266-71.

[16] Avall-Lundqvist EH, Silfverswärd C, Aspenblad U, Nilsson BR, Auer GU. The impact of tumour angiogenesis, p53 overexpression and proliferative activity (MIB-1) on survival in squamous cervical carcinoma. Eur J Cancer 1997;33:1799-804.

[17] Rajkumar T, Rajan S, Baruah RK, Majhi U, Selvaluxmi G, Vasanthan A. Prognostic significance of Bcl-2 and p53 protein expression in stage IIB and IIIB squamous cell carcinoma of the cervix. Eur J Gynaecol Oncol 1998;19:556-60.

[18] Giarnieri E, Mancini R, Pisani T, Alderisio M, Vecchione A. Msh2, Mlh1, Fhit, p53, Bcl-2, and Bax expression in invasive and in situ squamous cell carcinoma of the uterine cervix. Clin Cancer Res 2000;6:3600-6.

[19] Wootipoom V, Lekhyananda N, Phungrassami T, Boonyaphiphat P, Thongsuksai P. Prognostic significance of Bax, Bcl-2, and p53 expressions in cervical squamous cell carcinoma treated by radiotherapy. Gynecol Oncol 2004;94:636-42.

[20] Helland A, Holm R, Kristensen G, Kaern J, Karlsen F, Trope C, et al. Genetic alterations of the TP53 gene, p53 protein expression and HPV infection in primary cervical carcinomas. J Pathol 1993;171:105-14.

[21] Munakata S, Watanabe O, Ohashi K, Morino H. Expression of Fas ligand and bcl-2 in cervical carcinoma and their prognostic significance. Am J Clin Pathol 2005;123:879-85.

[22] Tjalma W, De Cuyper E, Weyler J, Van Marck E, De Pooter C, Albertyn G, et al. Expression of bcl-2 in invasive and in situ carcinoma of the uterine cervix. Am J Obstet Gynecol 1998;178:113-7.

[23] Aletra C, Ravazoula P, Scopa C, Kounelis S, Sotiropoulou G, Kourounis G, et al. Expression of bcl-2 and bax in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Eur J Gynaecol Oncol 2000;21:494-8.

[24] Crawford RA, Caldwell C, Iles RK, Lowe D, Shepherd JH, Chard T. Prognostic significance of the bcl-2 apoptotic family of proteins in primary and recurrent cervical cancer. Br J Cancer 1998;78:210-4.

[25] Choudhury M, Singh S. Detection of HPV16 and 18 by in situ hybridization in precancerous and cancerous lesions of cervix. Indian J Pathol Microbiol 2006;49:345-7.

[26] Menon MM, Simha MR, Doctor VM. Detection of human papillomavirus (HPV) types in precancerous and cancerous lesions of cervix in Indian women: A preliminary report. Indian J Cancer 1995;32:154-9.

p53 and bcl2 expression in malignant and premalignant lesions of uterine cervix and their correlation with human papilloma virus 16 and 18

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