Cancerization of cutaneous flap reconstruction for oral squamous cell carcinoma: report of three cases studied with the mtDNA D-loop sequence analysis.

AIMS: Tissue defects, resulting from surgical resection of oral squamous cell carcinoma (OSCC), are reconstructed routinely with skin grafts. OSCC arising from the grafted skin has been described; however, it is still unclear whether primary and second tumours have a common clonal origin. The aim of this study was to evaluate the clonal relationship between the primary OSCC and secondary neoplastic changes appearing in the skin graft in three patients, by screening the mitochondrial DNA D-loop region (mtDNA). METHODS AND RESULTS: In all three cases, the neoplastic lesions arising in the skin graft showed a clonal relationship with the previous OSCC and, on the basis of the results obtained by mtDNA analysis, could be considered to be a recurrence of the primary OSCC rather than a second primary OSCC. CONCLUSIONS: Starting from a field of genetically altered cells in the oral mucosa, the spread of the clonal cell population to the cutaneous flap might be stimulated by cytokines produced by the grafted skin. More studies are needed to evaluate the molecular relationship between primary and second OSCC to identify patients at higher risk of developing a second tumour in the skin graft.

p63 expression in salivary gland tumors: role of DeltaNp73L in neoplastic transformation.

To illustrate the role of p63 and its truncated variants in salivary gland tumors, 23 consecutive tumors and 6 normal salivary glands were studied immunohistochemically with anti-p63 antibody and by reverse transcriptase (RT) and nested polymerase chain reaction (PCR) to detect p63 isoform expression. Normal salivary glands: p63 antibody-stained basal and myoepithelial cells; by RT and nested PCR, the 2 main isoforms were present, whereas DeltaNp73L was absent. Tumors: p63 antibody was positive in the following: Warthin tumor (WT) (3/3), oncocytoma (OC) (1/1), pleomorphic adenoma (PA) (7/7), polymorphous-low-grade adenocarcinoma (PLGA) (3/3), adenoid-cystic carcinoma (ADCC)(3/4), epithelial-myoepithelial-cell carcinoma (EMC) (1/1), and myoepithelial-cell carcinoma (MCC) (1/1). By RT and nested PCR all tumors expressed p63 irrespective of their morphologic differentiation. The DeltaNp73L isoform was present in tumoral tissue but absent in normal salivary gland. These data suggest that p63, particularly its splice variant DeltaNp73L, is involved in the neoplastic transformation of salivary glands.

Pattern of p63 expression in squamous cell carcinoma of the oral cavity.

P63 is a recently discovered gene harbouring different isoforms by alternate splicing. The two main isoforms, TAp63 and Delta Np63, have opposite functions, being responsible for cell-cycle arrest and cell proliferation, respectively. In addition, new isoforms have been described with the same sequence as TAp63 and Delta Np63, but lacking exon 4 (Delta 4Tap63 and Delta Np73L). P63 as detected using immunohistochemistry is present in squamous cell carcinomas. To better define the role of p63 in squamous cell carcinomas of the oral cavity (OSCC), 39 patients were investigated using immunohistochemical analysis with a monoclonal antibody recognising all p63 isoforms and an anti-Ki67 antibody. Reverse-transcription polymerase chain reaction (PCR) and nested PCR were also performed using isoform-specific primers to evaluate the p63 mRNA expression pattern. Using immunohistochemistry, p63 was always present in OSCC, and its distribution was similar to that of Ki67. The percentage of positive cells increased from normal to neoplastic mucosa, but there was no relationship between the number of p63 positive cells and prognosis. P63 mRNA was found in all patients. The truncated isoforms Delta 4TAp63 and Delta Np73L were more frequently expressed in patients presenting with metastases. Delta Np73L was found in 66.6% of tumours with lymph-node metastases, but in only 33.3% of those devoid of lymph-node metastases at presentation. An impaired expression of the p63 isoforms might favour cell proliferation and indirectly enhance the metastasising capacity of OSCC.

Signet ring cell tumor of the minor salivary gland exhibiting benign behavior.

Signet ring cell (SRC) carcinomas are usually aggressive malignancies, arising most frequently in the stomach and gastrointestinal tract, but also, although less often, in other organs such as the breast, bladder, and lungs. They are particularly unusual in the salivary glands, and the aim of the present study is to report a case of a tumor of the minor salivary glands of the lower lip composed largely of SRCs but which displayed benign clinical behavior.

E-cadherin loss and Delta Np73L expression in oral squamous cell carcinomas showing aggressive behavior.

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 (Delta Np63) with immunohistochemistry. 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 Delta Np73L. RESULTS: E-cadherin expression was the most powerful parameter related to the presence of lymph node metastases at presentation. Twenty-four of 38 (63%) cases showing low E-cadherin 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 maintained when a low expression of E-cadherin was associated with immunohistochemical high expression of DeltaNp63. The association between low E-cadherin expression and Delta Np73L (as seen with reverse transcriptase-polymerase chain reaction) was highly predictive for developing lymph node metastases, especially 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-cadherin expression and presence of Delta Np73L. CONCLUSION: This study shows that low E-cadherin expression is useful for predicting lymph node metastases in cases of OSCC. The predictive value is enhanced when low E-cadherin positivity is associated with DeltaNp63 and Delta Np73L expression.