Tumor thickness influences prognosis of T1 and T2 oral cavity cancer--but what thickness?

BACKGROUND: Previous studies have demonstrated that tumor thickness might influence prognosis in oral cancer, but the significant point at which outcome changes has varied from 1.5 mm to 6 mm. The clinical relevance of thickness remains unclear, and a reproducible prognostic "breakpoint" needs to be defined. METHODS: Tumor thickness was measured in 145 oral cavity squamous cancers, clinically staged T1 (n = 62) or T2 (n = 83). Clinical and pathologic data were collected prospectively between 1988 and 2000, but thickness was measured on paraffin sections for this study. Minimum follow-up was 2 years, and thickness was correlated with local control, cervical node involvement, and survival. Patients with clinically positive nodes (n = 21) were not excluded. Overall, 55 patients had pathologic node involvement at some time in their disease. RESULTS: Median tumor thickness was 6.2 mm, and there was little variation between sites: tongue, 6.4 mm; floor of mouth, 6.6 mm; and other sites, 5.7 mm. Median thickness for T1 tumors was 4.3 mm, significantly less than the T2 group, 8 mm (p <.01). Median thickness also varied significantly for tumors with associated nodal disease (8.5 mm) and without nodal disease (5.8 mm) (p <.01). Prognosis changed significantly at a cutoff of 4 mm with local control, nodal disease, and survival rates of 91%, 8%, and 100%, respectively, for tumors <4 mm compared with 84%, 48%, and 74% for those 4 mm or more thick (p <.01). Subgrouping greater than and less than 3 mm and 5 mm also showed a difference but with poorer discrimination. Thickness and pathologic nodal involvement were highly significant independent prognostic factors. CONCLUSIONS: Tumor thickness is a highly significant, objectively measurable prognostic factor in early stage oral cancers. There is a need to standardize techniques of measurement to allow a multi-institutional study to be carried out. This will facilitate the development of strategies aimed at improving the outcome of higher risk patients.

Markers for the development of early prostate cancer.

Biochemical and genetic changes precede histologically identifiable changes accompanying cell transformation often by months or years. De-expression of the extracellular matrix adhesive glycoprotein tenascin and the cell-to-cell adherent protein E-cadherin have been suggested as markers of early neoplastic change in prostate epithelial cells. Previous studies have been inconclusive, probably due to epitope masking. This study examined 2,378 biopsy cores from 289 prostates using a heat antigen retrieval protocol at low pH to improve the accuracy of detection. Tenascin and E-cadherin de-expression was correlated with purinergic receptor and telomerase-associated protein labelling, as well as prostate-specific antigen (PSA) levels and Gleason scores. E-cadherin was a poor marker, as it was expressed in all lesions except carcinomas of the highest Gleason score. Tenascin was maximally expressed in the extracellular matrix and acinar basement membrane in normal and prostatic intraepithelial neoplasia tissue. In prostate cancer tissue, tenascin expression did not correlate with Gleason score but was significantly de-expressed as purinergic receptor and telomerase-associated protein expression increased. Marked changes in tenascin, telomerase-associated protein, and purinergic receptor expression were apparent before any histological abnormalities were visible by haematoxylin and eosin (H&E) stain, making these potential markers for early and developing prostate cancer. Moreover, the potential increased accuracy of diagnosis of underlying prostate cancer using purinergic receptor translocation (PRT) assessment suggests that PSA levels may be more accurate than has generally been supposed when apparent false negatives arising from H&E-based diagnoses are correctly categorized.

Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous carcinoma of the parotid gland.

BACKGROUND: Metastatic cutaneous cancer is the most common parotid malignancy in Australia, with metastatic squamous carcinoma (SCC) occurring most frequently. There are limitations in the current TNM staging system for metastatic cutaneous malignancy, because all patients with nodal metastases are simply designated N1, irrespective of the extent of disease. The aim of this study was to analyze the influence of clinical stage, extent of surgery, and pathologic findings on outcome after parotidectomy for metastatic SCC by applying a new staging system that separates metastatic disease in the parotid from metastatic disease in the neck. METHODS: A prospectively documented series of 87 patients treated by one of the authors (COB) over 12 years for clinical metastatic cutaneous SCC involving the parotid gland and a minimum of 2 years follow-up was analyzed. These patients were all previously untreated and were restaged according to the clinical extent of disease in the parotid gland in the following manner. P1, metastatic SCC of the parotid up to 3 cm in diameter; P2, tumor greater than 3 cm up to 6 cm in diameter or multiple metastatic parotid nodes; P3, tumor greater than 6 cm in diameter, VII nerve palsy, or skull base invasion. Neck disease was staged in the following manner: N0, no clinical metastatic disease in the neck; N1, a single ipsilateral metastatic neck node less than 3 cm in diameter; N2, multiple metastatic nodes or any node greater than 3 cm in diameter. RESULTS: Clinical P stages were P1, 43 patients; P2, 35 patients; and P3, 9 patients. A total of 21 patients (24%) had clinically positive neck nodes. Among these, 11 were N1, and 10 were N2. Conservative parotidectomies were carried out in 71 of 87 patients (82%), and 8 of these had involved surgical margins (11%). Radical parotidectomy sacrificing the facial nerve was performed in 16 patients, and 6 (38%) had positive margins, (p <.01 compared with conservative resections). Margins were positive in 12% of patients staged P1, 14% of those staged P2, and 44% of those staged P3 (p <.05). Multivariate analysis demonstrated that increasing P stage, positive margins, and a failure to have postoperative radiotherapy independently predicted for decreased control in the parotid region. Survival did not correlate with P stage; however, many patients staged P1 and P2 also had metastatic disease in the neck. Clinical and pathologic N stage both significantly influenced survival, and patients with N2 disease had a much worse prognosis than patients with negative necks or only a single positive node. Independent risk factors for survival by multivariate analysis were positive surgical margins and the presence of advanced (N2) clinical and pathologic neck disease. CONCLUSIONS: The results of this study demonstrate that patients with metastatic cutaneous SCC in both the parotid gland and neck have a significantly worse prognosis than those with disease in the parotid gland alone. Furthermore, patients with cervical nodes larger than 3 cm in diameter or with multiple positive neck nodes have a significantly worse prognosis than those with only a single positive node. Also, the extent of metastatic disease in the parotid gland correlated with the local control rate. The authors recommend that the clinical staging system for cutaneous SCC of the head and neck should separate parotid (P) and neck disease (N) and that the proposed staging system should be tested in a larger study population.