Abstract
Background
Histologically, tumors of the anal region are either keratinizing (K) or non-keratinizing (NK) squamous cell carcinomas (SCCA). We hypothesized that these two variants might represent, not only morphologically, but also biologically, dissimilar malignancies. The present study was undertaken to compare the expression of apoptosis-regulating proteins Bcl-2 and p53 in K versus NK SCCA.
Methods
We performed an immunohistochemical analysis on 98 pre-treatment biopsies of patients with anal canal cancers. Tissue sections were examined immunohistochemically for expression of proteins Bcl-2 (clone 124, DAKO, 1:100) and p53 (clone DO7, DAKO, 1:200). Expression of p53 and Bcl-2 was considered positive when >5% of tumor cells were stained. Tumor histology was correlated with protein expression as well as with other clinical variables.
Results
There were 64 NK and 34 K SCC. The proportion of Bcl-2 positive tumors was statistically higher in NK carcinomas (51.5 vs. 23.5%, p=0.009). In addition, women were more likely than men to present with NK carcinomas (71 vs. 45%, p=0.03) as well as with Bcl-2 positive tumors (47 vs. 29%, p=0.05). The more distal the tumor is (anal margin), the more frequently the keratinizing subtype is observed (87 vs. 23%, p=0.0002). By contrast, there was no correlation between p53 and tumor histology (p=0.83).
Conclusions
Our data demonstrate that non-keratinizing and keratinizing SCCA differ in their Bcl-2 expression. In addition, significant differences were observed in the distribution of these two histological subtypes according to gender and tumor sublocation. These findings may indicate possible differences in the carcinogenesis process of these two histological subtypes.
Similar content being viewed by others
References
Ryan DP, Compton C, Mayer RJ (2000) Carcinoma of the anal canal. N Engl J Med 342:792–800
Fuchshuber P, Rodriguez-Bigas M, Weber T, Petrelli NJ (1997) Anal canal and perianal epidermoid cancers. J Am Coll Surg 185:494–505
Nigro ND (1996) Neoplasms of the anus and anal canal. In: Condon RE (ed) The colon, 4th edn. Saunders, Philadelphia, pp 355–367
Ryan DP, Mayer RJ (2000) Anal carcinoma: histology, staging, epidemiology, treatment. Curr Opin Oncol 12:345–352
Gervaz P, Allal A, Villiger P, Buhler L, Morel P (2003) Squamous cell carcinoma of the anus. Another sexually transmitted disease. Swiss Med Wkly 133:353–359
Frisch M, Glimelius B, van den Brule AJC, Wohlfart J, Meijer CJ et al (1997) Sexually transmitted infection as a cause of anal cancer. N Engl J Med 337:1350–1358
Tilston P (1997) Anal human papillomavirus and anal cancer. J Clin Pathol 50:625
Frisch M, Fenger C, van den Brule AJ, Sorensen P, Meijer CJ et al (1999) Variants of squamous cell carcinoma of the anal canal and perianal skin and their relation to human papillomaviruses. Cancer Res 59:753–757
Grace VM, Shalini JV, Lekha TT, Devaraj SN, Devaraj H (2003) Co-overexpression of p53 and bcl-2 proteins in HPV-induced squamous cell carcinoma of the uterine cervix. Gynecol Oncol 91:51–58
Tjalma WA, Weyler JJ, Bogers JJ, Pollefliet C, Baay M et al (2001) The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer. Eur J Obstet Gynecol Reprod Biol 97:223–230
Sultana H, Kigawa J, Kanamori Y, Itamochi H, Oishi T et al (2003) Chemosensitivity and p53-Bax pathway-mediated apoptosis in patients with uterine cervical cancer. Ann Oncol 14:214–219
Fenger C, Frisch M, Marti MC, Parc R (2000) Tumours of the anal canal. In: Hamilton SR, Aaltonen LA (eds) World Health Organization classification of tumours: pathology and genetics of tumours of the digestive system. IARC, Lyon, pp 146–155
Myerson RJ, Karnell LH, Menck HR (1997) The national cancer data base report on carcinoma of the anus. Cancer 80:805–815
Schlienger M, Krzisch C, Pene F, Marin JL, Gindrey-Vie B et al (1989) Epidermoid carcinoma of the anal canal: treatment results and prognostic variables in a series of 242 cases. Int J Radiat Oncol Biol Phys 17:1141–1151
Fenger C (2002) Prognostic factors in anal carcinoma. Pathology 34:573–578
Kurvinen K, Syrjanen K, Syrjanen S (1996) P53 and bcl-2 proteins as prognostic markers in human papillomavirus-associated cervical lesions. J Clin Oncol 14:2120–2130
Crawford RA, Caldwell C, Iles RK, Lowe D, Shepherd JH et al (1998) Prognostic significance of the bcl-2 apoptotic family of proteins in primary and recurrent cervical cancer. Br J Cancer 78:210–214
Tjalma W, Weyler J, Goovaerts G, De Pooter C, Van Marck E et al (1997) Prognostic value of bcl-2 expression in patients with operable carcinoma of the uterine cervix. J Clin Pathol 50:33–36
Allal AS, Waelchli L, Bründler M-A (2002) Prognostic value of apoptosis-regulating proteins in anal carcinoma patients. ESTRO 21st Meeting, Praha 17–21 September 2002. Radiother Oncol 64 [Suppl 1]:152
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Allal, A.S., Bründler, MA. & Gervaz, P. Differential expression of anti-apoptotic protein Bcl-2 in keratinizing versus non-keratinizing squamous cell carcinoma of the anus. Int J Colorectal Dis 20, 161–164 (2005). https://doi.org/10.1007/s00384-004-0651-z
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00384-004-0651-z