Prognostic factors in medullary thyroid carcinomas.Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content

Abstract

Patients with medullary thyroid carcinomas (MTC) were analyzed according to age, sex, and tumor stage. In addition, the MTC were screened for the predominant histologic pattern, immunocytochemical spectrum (60 tumors), and DNA content (DNA cytophotometry and DNA flow cytometry, 25 tumors). These findings were correlated with follow-up data available for 45 of these patients. Fortyeight percent of the tumors revealed a polygonal cell pattern, whereas 22% showed spindle-cell predominance. All tumors contained cytokeratin, chromogranin A, and calcitonin (CT). Calcitonin gene-related peptide (CGRP) was present in 92%, carcinoembryonic antigen (CEA) in 77%, neuron-specific enolase (NSE) in 75%, and vimentin in 53% of cases. Positivity for neurotensin, somatostatin, neurofilaments, bombesin, and alpha human chorionic gonadotropin (a-hCG) and serotonin ranged between 3% and 27%. All MTC were negative for substance P, adrenocorticotropic hormone (ACTH), thyroglobulin (TG), or S-100 protein. h l recurrences and regional lymph node metastases revealed identical staining patterns as the primaries. Prognosis of MTC was found not to be related to histologic features (dominant architectural pattern, cellular shape, presence of amyloid deposits) or immunocytochemical pattern. Instead, survival was significantly correlated to age, sex, and stage of disease. The best prognosis was seen in women younger than 40 years and revealing an early stage of disease. DNA measurements added valuable information in assessing the prognosis of MTC. Cancer 61:806-816, 1988. EDULLARY THYROID carcinoma (MTC) com-M prises only 3% to 12%' of all thyroid carcinomas. Despite its rarity it has attracted great attention because of its distinctive biological, morphologic, and functional features. Medullary thyroid carcinoma occurs both in a sporadic and inherited form and has an almost equal sex ratio.'-3 Its biological behavior is generally regarded to be intermediate between the anaplastic and the differentiated thyroid carcinomas. However, patients with MTC show great variability in survival, which can vary from months to 30 years after diagnosis.' Due to the From the *Institutes of Pathology, University of Hamburg, General Hospitals ?Hamburg-Altona and §Hamburg-Harburg. West Germany. the IlUniversity of Basel, Switzerland. and the $ tumor's rarity, investigations of a correlation between clinicopathologic criteria and prognosis in a large series of MTC patients are sparse. The current study therefore relates detailed morphologic features, immunocyto-chemical data, DNA content, tumor stage, age, and sex to the survival of 45 patients with MTC. Materials and Methods Formalin-fixed, paraffin-embedded material obtained from surgical specimens of 60 primary MTC was analyzed , In 13 of these cases, material of local recurrences (n = 6) and/or regional lymph node metastases (n = 9) also was available. Five lymph node metastases had been removed together with the primary, whereas the remaining four metastases and the local recurrences had been resected betw...

Long-term outcome of medullary thyroid carcinoma in patients with normal postoperative medical imaging

“…However, the 10-year overall survival rate varied widely among series, from 55 up to 100% respectively (Rougier et al, 1983;Saad et al, 1984;Schroder et al, 1988;Raue et al, 1993;Dottorini et al, 1996;Scopsi et al, 1996;Bergholm et al, 1997;Modigliani et al, 1998). As therapy should be adapted to the prognosis of the disease, the identification of patients at high risk of relapse is essential.…”

“…In patients with elevated postoperative basal CT level, the 5-year relapse-free survival rate was 61%, similar to that reported by van Heerden et al (1990). The prognostic factors for survival of MTC patients include the age at diagnosis, the gender and the TNM classification (Schroder et al, 1988;Raue et al, 1993;Dottorini et al, 1996;Scopsi et al, 1996;Bergholm et al, 1997;Modigliani et al, 1998;Kebebew et al, 2000a). Data concerning MTC patients with normal postoperative imaging are few.…”

“…Node status was identified as a prognostic factor in the univariate analysis in our study and in others (Schroder et al, 1988;van Heerden et al, 1990;Raue et al, 1993;Dottorini et al, 1996;Scopsi et al, 1996;Bergholm et al, 1997;Modigliani et al, 1998;Hyer et al, 2000;Kebebew et al, 2000a). In another study, with rising numbers of metastatic lymph node, gross distant metastases occurred more frequently and postoperative basal CT level was less often normalised (Machens et al, 2000).…”

“…Five and 10-year overall survival rates in MTC patients without initial distant metastases range between 60 -100% and 55 -100%, respectively, suggesting that an aggressive therapeutic approach may not be appropriate in all patients (Rougier et al, 1983;Saad et al, 1984;Schroder et al, 1988;Raue et al, 1993;Dottorini et al, 1996;Scopsi et al, 1996;Bergholm et al, 1997;Modigliani et al, 1998). In patients with elevated plasma CT level and with no evidence of gross residual disease after initial surgery, the rate of clinical or imaging-detected relapses is about 40% during the subsequent follow-up (Rougier et al, 1983;Van Heerden et al, 1990).…”

Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas

“…Schröder et al (1988) found that most MTC have a diploid DNA pattern, and that a benign disease course was twice as frequent in patients with diploid tumours compared with aneuploid tumours. Conversely, the results presented by Lindsay (1970) seemed to be more consistent with aneuploidy in MTC.…”