In papillary carcinoma, it should be noted that histologic vascular invasion may be considered as a sign of an increased tendency toward hematogenic invasion and consequent increase in the relative percentage of metastases; ultimately, this means a poorer prognosis. In the presence of risk factors indicating a possible increase in biologic aggressiveness, adequate postoperative treatment and close follow up become essential.

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Recently, the Italian Network of Cancer Registries analyzed 5101 cases of thyroid carcinoma showing a reduction of mortality rate of 4%/year. This prompts us to evaluate the temporal trend in tumor size, age at diagnosis, and histology in a retrospective analysis of 500 thyroid cancers diagnosed over 20 years. Thyroid cancers were divided in two groups. The first included 193 cases diagnosed from 1985 to 1994, and the second 307 from 1995 to 2004. The size of all tumors was significantly reduced from 30 +/- 1.4mm in the first group to 15 +/- 0.8mm in the second group. In particular, papillary thyroid carcinoma (PTC) size decreased from 28 +/- 1.2mm to 14 +/- 0.8mm and follicular carcinoma from 40 +/- 6.3mm to 17 +/- 4.5 mm. Age at diagnosis of all carcinomas increased significantly from 40 +/- 1.3 years in the first group to 48 +/- 0.9 years in the second group. Analysis of the histological types revealed a significant increase of PTC rate in the second decade from 82% to 92% and a concomitant reduction of anaplastic thyroid carcinoma (ATC) from 3.7% to 1.0%. Moreover, a significant increase of micro-PTC rate, from 7.3% to 36.4%, was observed. In conclusion, it may be speculated that the above mentioned decreased mortality rate for thyroid carcinoma could be related to the significant reduction with time of cancer size, to the progressive increase of PTC rate and to the reduction of ATC rate. These data, if confirmed in other series, underscore the importance of evaluating thyroid nodules smaller than 10mm and corroborate recent findings suggesting that age be reconsidered as an independent prognostic factor for differentiated thyroid cancers.

Met protein, the high affinity receptor for hepatocyte growth factor (HGF), was highly expressed by the tumour cells of 64 well-differentiated papillary carcinomas of the thyroid. The p145 mature form and the p170 precursor form of the protein were both isolated from the tumours. Enhanced expression of Met protein was associated with a 9.5 +/- 5-fold increase in MET RNA transcript levels, suggesting increased transcription of the gene. In the same tumours, the levels of RNA transcripts for hypoxia inducible factor-1 (HIF-1), a potent stimulator of met gene transcription, were 4.5 +/- 3-fold higher than those present in the surrounding normal thyroid tissues. HIF-1 is generally induced by hypoxia. Histological features suggestive of a hypoxia were observed in 37 of 50 tumours and included coagulative necrosis, psammoma bodies, cystic changes, intratumoural haemorrhage, and hyalinization of the fibrous stroma. Immunostaining for Met protein was particularly intense in some cells located at the tumour periphery which were characterized by an invasive phenotype. Microdissection of tumour cell nests from the invading front revealed that the levels of RNA transcripts for MET/HIF were higher than in the centre of the tumour in four of nine cases. Taken together, the findings of this study suggest that HIF-1, perhaps driven by hypoxia, may be one of the factors leading to the increased transcription of met gene in papillary carcinoma and that this event is often more pronounced at the tumour periphery.

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