Multiple oral squamous epithelial lesions: are they genetically related?

The development of second primary tumors (SPTs) in patients with head and n eck squamous cell carcinoma (HNSCC) has become an increasingly important fa ctor in clinical treatment decison, Currently, clinical and histologic para meters are used to determine whether or not SPT is present. Recent studies suggest that many SPTs in the upper aerodigestive tract have a common clona l origin, challenging the longstanding multiclonal origin concept, To deter mine genetic relationships among multiple oral cancerous and precancerous l esions (MOCP), we analysed 100 lesions from 26 Japanese patients, Lesion de velopment was synchronous and metachronous. We looked for patterns of micro satellite alterations (MA) using seven markers at chromosomes 3p14, 9p21, a nd 17p13, where MA occurs early in oral carcinogenesis. Loss of heterozygos ity (LOH) was found in 52.6% (41/78), 62.5% (60/96), and 59.3% (32/54) of i nformative MOCP at 3p14, 9p21, and 17p13, respectively, Microsatellite inst ability (MI) was observed in II, 26 and 13% of the samples at 3p14, 9p21, a nd 17p13 markers, respectively. Patterns of MA were concordant in only nine (14%) of 63 lesions from four (18%) of 22 patients who initially presented with noninvasive lesions. However, two of four patients with invasive canc er as indexed lesion showed 16 (43%) clonally related MOCP among 37 lesions (P=0.003). The results suggest that the majority of MOCP arise from clonal ly independent cells affected by field cancerization. However, the probabil ity of mucosal spread of clonal malignant or premalignant cells may increas e along with malignant progression.