ORIGINAL ARTICLE E-CADHERIN LOSS AND DNP73L EXPRESSION IN ORAL SQUAMOUS CELL CARCINOMAS SHOWING AGGRESSIVE BEHAVIOR Maria P. Foschini, MD, 1 Roberto Cocchi, MD, 2 Luca Morandi, BSc, PhD, 1 Gianluca Marucci, MD, 1 Maria G. Pennesi, MD, 2 Alberto Righi, MD, 1 Anna L. Tosi, MD, 1 Dario de Biase, BSc, 1 Annalisa Pession, BSc, 1 Lucio Montebugnoli, MD 3 1 Institute of Pathological Anatomy, University of Bologna, Bellaria Hospital, Bologna, Italy. E-mail: mariapia.foschini@ausl.bologna.it 2 Department of Maxillo-Facial Surgery, Bellaria Hospital, Bologna, Italy 3 Department of Oral Sciences, University of Bologna, Bologna, Italy Accepted 11 April 2008 Published online 14 August 2008 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20908 Abstract: Background. This article sought to investigate the existence of parameters useful for predicting lymph node metastases in cases of surgically resected oral squamous cell carcinomas (OSCCs). Methods. Fifty-eight cases were studied for E-cadherin and the truncated dominant-negative isoform of p63 (DNp63) with immuno- histochemistry. In addition, the p63 gene expression profile was evaluated by reverse transcriptase-polymerase chain reaction (RT- PCR) to disclose the presence of the truncated variant DNp73L. Results. E-cadherin expression was the most powerful pa- rameter related to the presence of lymph node metastases at presentation. Twenty-four of 38 (63%) cases showing low E-cad- herin expression had lymph node metastases at presentation compared with 5 of 20 (25%)(p <.01) cases showing high E- cadherin expression. The high predictive value was also main- tained when a low expression of E-cadherin was associated with immunohistochemical high expression of DNp63. The associa- tion between low E-cadherin expression and DNp73L (as seen with reverse transcriptase-polymerase chain reaction) was highly predictive for developing lymph node metastases, espe- cially in small tumors (T1\T2). When this association occurred, metastases developed in 62.5% of cases during the follow-up compared with 16.1% in those which did not show low E-cad- herin expression and presence of DNp73L. Conclusion. This study shows that low E-cadherin expres- sion is useful for predicting lymph node metastases in cases of OSCC. The predictive value is enhanced when low E-cadherin positivity is associated with DNp63 and DNp73L expression. V V C 2008 Wiley Periodicals, Inc. Head Neck 30: 1475–1482, 2008 Keywords: squamous cell carcinoma; p63; DNp73L; lymph node metastasis; E-cadherin DNA array studies have shown that oral squa- mous cell carcinomas (OSCCs) with metastases have a gene expression profile different from that of OSCC without metastases. 1 This has led to the formulation of the ‘‘metastatic gene expression profile.’’ 2 Accordingly, primary OSCC harboring metastases carry genetic alterations favoring the metastatic process and, therefore, an accurate genetic portrait can be helpful in predicting cases of OSCC with an elevated probability of leading to early and\or late metastases. The cDNA array technique is difficult, expen- sive, and not easily applicable to daily diagnostic Correspondence to: M. P. Foschini V V C 2008 Wiley Periodicals, Inc. Aggressive Oral Squamous Cell Carcinoma HEAD & NECK—DOI 10.1002/hed November 2008 1475