Differential expression of anti-apoptotic protein Bcl-2 in keratinizing versus non-keratinizing squamous cell carcinoma of the anus.
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.
Allal
Abdelkarim S
AS
Division of Radiation Oncology, University Hospital Geneva, Rue Micheli-du-Crest 24, 1211 Geneva, Switzerland. abdelkarim.allal@hcuge.ch
Bründler
Marie-Anne
MA
Gervaz
Pascal
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012189:Retrospective Studies; D012737:Sex Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53