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. 2012 Feb 14;106(4):756-62.
doi: 10.1038/bjc.2011.548.

Expression of DSG1 and DSC1 are prognostic markers in anal carcinoma patients

M P Myklebust  1 , Ø Fluge, H Immervoll, A Skarstein, L Balteskard, O Bruland, O Dahl
Affiliations

Expression of DSG1 and DSC1 are prognostic markers in anal carcinoma patients

M P Myklebust et al. Br J Cancer. .

Abstract

Background: Our purpose was to investigate if dysregulation of cell adhesion molecules could be linked to prognosis in squamous cell carcinomas (SCCs) of the anal region.

Methods: Protein expression of desmoglein-1 (DSG1), desmocollin-1 (DSC1) and E-cadherin was studied by immunohistochemistry in a cohort of 53 anal carcinoma patients treated by radiation alone or combined with 5-fluorouracil and mitomycin C.

Results: Univariate analyses identified, among others, negative membranous DSG1 staining (P=0.009), negative cytoplasmic DSC1 staining (P=0.012) and negative DSG1 (membranous)+negative DSC1 (cytoplasmic) staining (P=0.004) to be associated with improved cancer-specific survival (CSS). On multivariate analyses positive DSG1 (membranous)+DSC1 (cytoplasmic) staining (HR 6.95, P=0.044), large tumour size and lymph node metastases (HR 6.44, P=0.004) and radiation without chemotherapy (HR 6.73 P=0.004) were associated with worse CSS. On univariate analysis, improved disease-free survival was associated with negative membranous staining of DSG1 (P=0.047), and negative DSG1 (membranous)+negative DSC1 (cytoplasmic) staining (P=0.025), among others.

Conclusion: Membrane negativity for DSG1 and cytoplasmic negativity for DSC1 are favourable markers for CSS in SCCs of the anal region.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immunohistochemical staining of normal anal mucosa and anal carcinomas (SCC) showing representative staining for DSG1 and DSC1. (A) DSG1 and (B) DSC1 staining in normal anal mucosa. (C) Positive membranous DSG1 in anal SCC. (D) Negative membranous DSG1 with weak perinuclear staining in anal SCC. (E) Positive cytoplasmic DSC1 in anal SCC.
Figure 2
Figure 2
Univariate survival analyses according to the Kaplan-Meier method. Kaplan-Meier plots showing anal cancer specific survival (CSS) with P-values from log-rank test. (A) DSG1 membranous negative vs membranous postive. (B) DSC1 cytoplasmic negative vs cytoplasmic positive, and (C) DSG1 membranous +DSC1 cytoplasmic staining assessed as one variable.
Figure 3
Figure 3
Cancer specific survival among the anal cancer patients when DSG1 membrane expression was stratified for E-cadherin expression. (A) DSG1 and cancer specific survival in patients with strong E-cadherin protein expression. (B) DSG1 and cancer specific survival in patients with weak E-cadherin expression. P-value=0.020 (pooled over strata).
See this image and copyright information in PMC

References

    1. Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson III AB, Thomas Jr CR, Mayer RJ, Haddock MG, Rich TA, Willett C (2008) Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 299: 1914–1921 - PubMed
    1. Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson III AB, Thomas Jr CR, Mayer RJ, Haddock MG, Rich TA, Willett CG (2010) Prognostic factors derived from a prospective database dictate clinical biology of anal cancer: the intergroup trial (RTOG 98-11). Cancer 116: 4007–4013 - PMC - PubMed
    1. Alazawi WO, Morris LS, Stanley MA, Garrod DR, Coleman N (2003) Altered expression of desmosomal components in high-grade squamous intraepithelial lesions of the cervix. Virchows Arch 443: 51–56 - PubMed
    1. Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, Peiffert D, van Glabbeke M, Pierart M (1997) Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 15: 2040–2049 - PubMed
    1. Ben-Josef E, Moughan J, Ajani JA, Flam M, Gunderson L, Pollock J, Myerson R, Anne R, Rosenthal SA, Willett C (2010) Impact of overall treatment time on survival and local control in patients with anal cancer: a pooled data analysis of Radiation Therapy Oncology Group trials 87-04 and 98-11. J Clin Oncol 28: 5061–5066 - PMC - PubMed

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