DNA damage marker phosphorylated histone H2AX is a potential predictive marker for progression of epithelial dysplasia of the oral cavity.

AIMS: To evaluate the relationships between immunohistochemical markers related to cellular senescence, cell proliferation and histological grade of epithelial dysplasia (OD) of the oral cavity. In addition, the predictive value of these markers for progression of OD was assessed. METHODS AND RESULTS: Retrospective immunohistochemical analyses were performed on 86 formalin-fixed paraffin-embedded specimens of OD and oral squamous cell carcinoma (OSCC) for Ki67, phosphorylated histone H2AX (γH2AX), p53, p16, trimethyl-histone H3 (Lys9) (H3K9me3) and cyclin D1 (CycD1). Three separate areas representing the highest severity of OD on each slide were annotated digitally by two independent pathologists. Mean automated histoscores of the selected markers were generated and compared to that of age-matched healthy controls (n = 24). Follow-up data of OD were retrieved and anonymized by a clinical team member and linked using unique participant identifiers. The median follow-up was 10.9 years (interquartile range: 10.1-11.5). Ki67 (P < 0.0001), γH2AX (P = 0.03) and p53 (P = 0.04) were increased significantly with higher histological grade of OD. γH2AX (P = 0.03), but not histological grade of OD (P = 0.73), was associated prospectively with disease progression. Using the median histoscore for γH2AX (median histoscore = 17) as a cut-off, histoscore ≥17 was associated with an increased risk of disease progression [hazard ratio (HR) = 3.15, 95% confidence interval (CI): 1.41-7.39, P = 0.0064]. CONCLUSIONS: Although proliferation marker Ki67, DNA damage/checkpoint markers γH2AX and p53 were increased in higher grade of OD, only γH2AX was predictive of disease progression. These observations may reflect the role of DNA replicative stress in the transformation from OD to OSCC. Larger studies should evaluate whether γH2AX can be used as a predictive marker of OD.

Use of Lugol's iodine in the resection of oral and oropharyngeal squamous cell carcinoma.

We evaluated the use of Lugol's iodine in achieving surgical margins free from dysplasia, carcinoma in situ, and invasive carcinoma by an observational study of two series of 50 consecutive patients having resection of oral and oropharyngeal squamous cell carcinoma (SCC) between November 2004 and March 2007. The standard group had resection of the primary tumour with a macroscopic 1cm margin and removal of adjacent visibly abnormal mucosa. The Lugol's iodine group had identical treatment with resection of any adjacent mucosa that did not stain after the application of Lugol's iodine (where this was feasible). In the standard group 16 patients (32%) had dysplasia, carcinoma in situ, or invasive SCC at a surgical margin. In the Lugol's iodine group two patients (4%) had dysplasia or carcinoma in situ; none had invasive SCC. Lugol's iodine is a simple, inexpensive, and apparently effective means of reducing the likelihood of unsatisfactory surgical margins in the resection of oral and oropharyngeal SCC.

Gamma tubulin: a promising indicator of recurrence in squamous cell carcinoma of the larynx.

OBJECTIVE: Centrosome amplification as detected by gamma tubulin (GT) immunostaining is associated with genetic instability and tumor aggressiveness. We assessed GT for its ability to predict recurrence of squamous cell carcinoma of the larynx (SCCL). STUDY DESIGN: Case series with chart review. MATERIALS AND METHODS: Five micron sections of 35 archival SCCL samples were subjected to antigen retrieval and immunostaining with antibody to GT. The keratin antibody CK5 served as a positive control for antigen retrieval, and tonsillar tissue was used as a negative control. RESULTS: Of the 35 tumors analyzed, 22 were associated with recurrence(R) and 13 were not (NR). Fourteen of the 22 R tumors, but 0 of 13 of the NR tumours had a GT staining score of 2+ or 3+ (P < 0.0002). GT was also related to recurrence in node-negative tumors (P < 0.006) but was unrelated to T stage (P = 0.726). CONCLUSIONS: GT staining appears to be a better predictor of tumor recurrence than T stage and also predicts recurrence in N0 tumors.