A comparative study of cell cycle mediator protein expression patterns in anaplastic and papillary thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is an extremely aggressive and rapidly fatal neoplasm. The aim of this study was to identify a limited cell cycle associated protein expression pattern unique to ATC and to correlate that pattern with clinical outcome. This represents one of the largest tissue micro-array projects comparing the cell cycle protein expression data of ATC to other well-differentiated tumors in the literature. Tissue microarrays were created from 21 patients with ATC and an age and gender matched cohort of patients with papillary thyroid carcinoma (PTC). Expression of epidermal growth factor receptor, cyclin D1, cyclin E, p53, p21, p16, aurora kinase A, opioid growth factor (OGF), OGF-receptor, thyroglobulin and Ki-67 was evaluated in a semi-quantitative fashion. Differences in protein expression between the cohorts were evaluated using chi-square tests with Bonferroni adjustments. Survival time and presence of metastasis at presentation were collected. The ATC cohort showed a statistically significant decrease (p < 0.05) in thyroglobulin expression and statistically significant increases (p < 0.05) in Ki-67 and p53 expression as compared with the PTC cohort. A trend toward loss of p16 and p21 expression was noted in the ATC cohort. A trend toward decreased survival was noted with p21 expression. These data indicate disruption of the normal cell cycle with aberrant expression of multiple protein markers suggesting increased proliferative activity and loss of control of cell cycle progression to G1 phase. These findings support the assertion that ATC may represent the furthest end of a continuum of thyroid carcinoma dedifferentiation.

Dyspnea as a prognostic factor in anaplastic thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer. In this study, we review a single institution's experience with ATC over past 34 years. Through retrospective review, we attempted to identify the prognostic factors affecting the survival at our institution. We reviewed the records of 33 patients diagnosed with ATC by pathology over the last three decades. At our institution, median age at diagnosis was 68 years, the male to female ratio was 1.1:1, mean survival was 10 months and median survival was 4.7 months. Thirty-nine percentage of patients were treated with chemotherapy and 52% received radiation treatment. Thirty-six percentage received both chemotherapy and radiation and 58% of patients were treated with surgical intervention. Four of the patients received surgical intervention with curative intent. Tracheotomy was performed in 40% of patients. Eight patients survived more than 10 months. Univariate analysis showed that age greater than 60 and dyspnea at presentation were associated with decreased survival and that surgical intervention was associated with increased survival. Multivariate analysis identified only dyspnea at the time of presentation to be a significant independent prognostic factor affecting the mortality. While long-term survival is possible in some patients, ATC has a poor prognosis despite the attempts at aggressive treatment. In this study, we report that dyspnea was the only independent factor found to negatively affect the survival. This finding is unique in our study and supports the role of using signs at the time of presentation as potential prognostic factors for those patients with this aggressive disease.

Anaplastic thyroid carcinoma in a young woman: a rare case of survival.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is rare but one of the most aggressive human cancers. It carries a dismal prognosis with average survival of 6 months. It is characteristically diagnosed in patients older than 60 years. We report the case of a young patient with ATC, in whom disease-free survival exceeds 2 years, and review the related literature. SUMMARY: A 26-year-old woman presented with a rapidly growing anterior neck mass. A neck computed tomography scan showed a 3.5-cm left thyroid mass extending into the lateral neck. Fine-needle aspiration biopsy showed a malignant tumor. A subsequent core biopsy showed an undifferentiated epithelial carcinoma. A total thyroidectomy and left modified radical neck dissection were performed. Histopathology and immunohistochemical analysis confirmed an ATC. Postoperatively, the patient received radiation with concurrent chemotherapy. Serial follow-up imaging studies showed no evidence of residual or recurrent disease or metastases, and patient remains alive, free of disease, over 2 years. CONCLUSION: ATC is usually a disease of the elderly but should be considered in the differential diagnosis of any patient who presents with a rapidly enlarging anterior neck mass. A rapid and thorough investigation should be initiated. This unusual case highlights that this aggressive thyroid cancer may occur in the young. It also emphasizes the role of aggressive surgery, if resectable.