Aerodigestive tract invasion by well-differentiated thyroid carcinoma: diagnosis, management, prognosis, and biology.

Objectives/Hypothesis: 1) To describe the clinical entity invasive well-differentiated thyroid carcinoma (IWDTC), 2) to determine prognostic factors for survival in patients with IWDTC, 3) to describe and compare types of surgical resection to determine treatment efficacy, 4) to offer a staging system and surgical algorithm for management of patients with IWDTC, 5) to examine alterations in expression of E-cadherin and β-catenin adhesion molecules in three groups of thyroid tissue and propose a cellular mechanism for invasion of the aerodigestive tract. Study Design: Basic science: quantification of expression of E-cadherin and β-catenin in three groups of thyroid tissue. Clinical: retrospective review of patients with IWDTC surgically treated and followed over a 45-year time period. Methods: Basic science: immunohistochemical staining was used with antibodies against E-cadherin and β-catenin in three groups of tissue: group 1, normal control thyroid tissue (n = 10); group 2, conventional papillary thyroid carcinoma (n = 20); group 3, IWDTC (n = 12). Intensity scores were given on the basis of protocol. One-way analysis of variance (ANOVA) was used to evaluate differences between groups. Post hoc ANOVA testing was completed. P < .05 was significant. Clinical: patients were divided into three surgical groups within the laryngotracheal subset: group 1, complete resection of gross disease (n = 34); group 2, shave excision (n = 75); group 3, incomplete excision (n = 15). Cox regression analysis was used to determine significance of prognostic factors. Kaplan-Meier plots were used to evaluate survival. P < .05 was significant. Results: Basic science: a significant difference between the three thyroid tissue groups for E-cadherin expression was demonstrated on one-way ANOVA testing. When controls were compared with either experimental group in post hoc ANOVA testing, differences between all groups were demonstrated (P < .001). For β-catenin, the intensities of the three groups were not different by one-way ANOVA testing. Similar nonsignificant results were found on post hoc ANOVA testing. Clinical: there was a statistically significant difference in survival for patients with and without involvement of any portion of the endolarynx or trachea (P < .01). There was a significant difference among all three surgical groups when compared (P < .001). When complete and shave groups were compared with gross residual group there was a significant decrease in survival in incomplete resection group (P < .01). Cox regression analysis demonstrated invasion of larynx and trachea were significant prognostic factors for poor outcome. The type of initial resection was significant on multivariate analysis. Removal of all gross disease is a major factor for survival. Conclusions: Basic science: there is a decrease in membrane expression of E-cadherin in IWDTC, and loss of this tumor suppressor adhesion molecule may contribute to the invasive nature of well-differentiated thyroid carcinomas. Clinical: laryngotracheal invasion is a significant independent prognostic factor for survival. Patients undergoing shave excision had similar survival when compared with those undergoing radical tumor resection if gross tumor did not remain. Gross intraluminal tumor should be resected completely. Shave excision is adequate for minimal invasion not involving the intraluminal surfaces of the aerodigestive tract.