Multiple oral squamous epithelial lesions: are they genetically related?

Abstract

The development of second primary tumors (SPTs) in patients with head and neck squamous cell carcinoma (HNSCC) has become an increasingly important factor in clinical treatment decison. Currently, clinical and histologic parameters are used to determine whether or not SPT is present. Recent studies suggest that many SPTs in the upper aerodigestive tract have a common clonal origin, challenging the longstanding multiclonal origin concept. To determine genetic relationships among multiple oral cancerous and precancerous lesions (MOCP), we analysed 100 lesions from 26 Japanese patients. Lesion development was synchronous and metachronous. We looked for patterns of microsatellite alterations (MA) using seven markers at chromosomes 3p14, 9p21, and 17p13, where MA occurs early in oral carcinogenesis. Loss of heterozygosity (LOH) was found in 52.6% (41/78), 62.5% (60/96), and 59.3% (32/54) of informative MOCP at 3p14, 9p21, and 17p13, respectively. Microsatellite instability (MI) was observed in 11, 26 and 13% of the samples at 3p14, 9p21, and 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 cancer 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 clonally independent cells a ected by ®eld cancerization. However, the probability of mucosal spread of clonal malignant or premalignant cells may increase along with malignant progression. Oncogene (2001) 20, 2235 ± 2242.

Overexpression of podoplanin in oral cancer and its association with poor clinical outcome

“…We have previously demonstrated that multiple oral premalignant lesions may be the result of the spreading of index lesions in some patients. 16 It would also be interesting to investigate whether podoplanin is involved in such process. …”

Clonality of multifocal urothelial carcinomas: 10 years of molecular genetic studies

“…72 As mentioned above, the majority of studies investigating multifocal urothelial lesions have demonstrated a monoclonal origin. However, there are several studies indicating that field cancerization contributes to urothelial p53, p53 gene mutation analysis; FISH, fluorescence in situ hybridization; MSI, detection of high-grade microsatellite instability using the Bethesda primer panel 76 and immunohistochemistry of mismatch repair proteins (oligoclonality was presumed only if 1 clone exhibited high-grade instability and the other did not).…”

Retracted: The evolution of predictive oncology and molecular‐based therapy for oral cancer prevention

“…[38][39][40][41] The multifocal nature of early oral carcinogenesis may hinder local treatment modalities. 7,37,38,42 In a recent study, we have demonstrated that cancer developed in the same location as did the preceding leukoplakia in 79% (37) of the 47 oral cancer patients.…”